Szerkesztő:Alfa-ketosav/5-HT2A-receptor

A Wikipédiából, a szabad enciklopédiából

Az 5-HT2A-receptor a szerotoninreceptorok családjába tartozó 5-HT2-receptorok típusa, G-protein-kapcsolt receptor (GPCR).[1] Sejtfelszíni receptor,[2] de a sejtben is sok helyen előfordul.[3]

A többi 5-HT2 receptorhoz hasonlóan Gq-protein-kapcsolt. Ez a szerotonin GPCR-einek fő akciósreceptor-altípusa, de az 5-HT2A gátolhat[4] bizonyos helyeken, például a látó- és orbitofrontális kérgen.[5] Először szerotonerg pszichedelikumok, például az LSD és a pszilocibin célpontjaként ismerték fel fontosságát, később az antipszichotikumok, különösen az atipikusak hatásának legaláb részleges mediációja miatt került előtérbe.

A posztszinaptikus 5-HT2A-receptor gyengítése a szelektív szerotoninújrafelvétel-gátlók és az atipikus antipszichotikumok krónikus bevitelekor jelentkező adaptív folyamat. Depresszív betegekben az 5-HT2A-receptor szintje a normálisnál nagyobb. Ezek alapján a nagy posztszinaptikus 5-HT2A-mennyiség érintett a depresszió patogenezisében.[6]

Paradoxical down-regulation of 5-HT2A receptors can be observed with several 5-HT2A antagonists.[7] Thus, instead of tolerance, reverse-tolerance would be expected from 5-HT2A antagonists. However, there is at least one antagonist at this site which has been shown to up-regulate 5-HT2A receptors.[7][8] Additionally, a couple of other antagonists may have no effect on 5-HT2A receptor number.[9] Nevertheless, upregulation is the exception rather than the rule. Neither tolerance nor rebound is observed in humans with regard to the slow-wave sleep (SWS) promoting effects of 5-HT2A antagonists.[10]

Signaling cascade[szerkesztés]

The 5-HT2A receptor is known primarily to couple to the Gαq signal transduction pathway. Upon receptor stimulation with agonist, Gαq and β-γ subunits dissociate to initiate downstream effector pathways. Gαq stimulates phospholipase C (PLC) activity, which subsequently promotes the release of diacylglycerol (DAG) and inositol triphosphate (IP3), which in turn stimulate protein kinase C (PKC) activity and Ca2+ release.[11]

History[szerkesztés]

5-HT receptors were split into two classes by John Gaddum and Picarelli when it was discovered that some of the serotonin-induced changes in the gut could be blocked by morphine, while the remainder of the response was inhibited by dibenzyline, leading to the naming of M and D receptors, respectively. 5-HT2A is thought to correspond to what was originally described as D subtype of 5-HT receptors by Gaddum and Picarelli.[12] In the era before molecular cloning, when radioligand binding and displacement was the only major tool, spiperone and LSD were shown to label two different 5-HT receptors, and neither of them displaced morphine, leading to naming of the 5-HT1, 5-HT2 and 5-HT3 receptors, corresponding to high affinity sites from LSD, spiperone and morphine, respectively.[13] Later it was shown that the 5-HT2 was very close to 5-HT1C and thus were grouped together, renaming the 5-HT2 into 5-HT2A. Thus, the 5-HT2 receptor family is composed of three separate molecular entities: the 5-HT2A (formerly known as 5-HT2 or D), the 5-HT2B (formerly known as 5-HT2F) and the 5-HT2C (formerly known as 5-HT1C) receptors.[14]

Distribution[szerkesztés]

5-HT2A is expressed widely throughout the central nervous system (CNS).[15] It is expressed near most of the serotonergic terminal rich areas, including neocortex (mainly prefrontal, parietal, and somatosensory cortex) and the olfactory tubercle. Especially high concentrations of this receptor on the apical dendrites of pyramidal cells in layer V of the cortex may modulate cognitive processes, working memory, and attention[16][17][18] by enhancing glutamate release followed by a complex range of interactions with the 5-HT1A,[19] GABAA,[20] adenosine A1,[21] AMPA,[22] mGluR2/3,[23] mGlu5,[24] and OX2 receptors.[25][26] In the rat cerebellum, the protein has also been found in the Golgi cells of the granular layer,[27] and in the Purkinje cells.[28][29]

In the periphery, it is highly expressed in platelets and many cell types of the cardiovascular system, in fibroblasts, and in neurons of the peripheral nervous system. Additionally, 5-HT2A mRNA expression has been observed in human monocytes.[30] Whole-body distribution of the 5-HT2A/2C receptor agonist, [11C]Cimbi-36 show uptake in several internal organs and brown adipose tissue (BAT), but it is not clear if this represents specific 5-HT2A receptor binding.[31]

Effects[szerkesztés]

Physiological processes mediated by the receptor include:

Ligands[szerkesztés]

Agonists[szerkesztés]

Sablon:Further Activation of the 5-HT2A receptor is necessary for the effects of the "classic" psychedelics like LSD, psilocin and mescaline, which act as full or partial agonists at this receptor, and represent the three main classes of 5-HT2A agonists, the ergolines, tryptamines and phenethylamines, respectively. A very large family of derivatives from these three classes has been developed, and their structure-activity relationships have been extensively researched.[45][46] Agonists acting at 5-HT2A receptors located on the apical dendrites of pyramidal cells within regions of the prefrontal cortex are believed to mediate hallucinogenic activity. Some findings reveal that psychoactive effects of classic psychedelics are mediated by the receptor heterodimer 5-HT2A–mGlu2 and not by monomeric 5-HT2A receptors.[47][48][32] However, newer research suggests that 5HT2A and mGlu2 receptors do not physically associate with each other, so the former findings have questionable relevance.[49] Agonists enhance dopamine in PFC,[18] enhance memory and play an active role in attention and learning.[50][51]

Full agonists[szerkesztés]

Partial agonists[szerkesztés]

Peripherally selective agonists[szerkesztés]

One effect of 5-HT2A receptor activation is a reduction in intraocular pressure, and so 5-HT2A agonists can be useful for the treatment of glaucoma. This has led to the development of compounds such as AL-34662 that are hoped to reduce pressure inside the eyes but without crossing the blood–brain barrier and producing hallucinogenic side effects.[77] Animal studies with this compound showed it to be free of hallucinogenic effects at doses up to 30 mg/kg, although several of its more lipophilic analogues did produce the head-twitch response known to be characteristic of hallucinogenic effects in rodents.[78]

Antagonists[szerkesztés]

Antagonists and cardiovascular disease[szerkesztés]

Increased 5-HT2A expression is observed in patients with coronary thrombosis, and the receptor has been associated with processes that influence atherosclerosis.[90] As the receptor is present in coronary arteries[91] and capable of mediating vasoconstriction, 5-HT2A has also been linked to coronary artery spasms.[92] 5-HT antagonism, therefore, has potential in the prevention of cardiovascular disease, however, no studies have been published so far.[90]

Inverse agonists[szerkesztés]

  • AC-90179 – potent and selective inverse agonist at 5-HT2A, also 5-HT2C antagonist.[93][94]
  • Nelotanserin (APD-125) – selective 5-HT2A inverse agonist developed by Arena Pharmaceuticals for the treatment of insomnia. APD-125 was shown to be effective and well tolerated in clinical trials.[95]
  • Eplivanserin (Sanofi Aventis) – sleeping pill that reached phase II trials (but for which the application for approval was withdrawn), acts as a selective 5-HT2A inverse agonist.
  • Pimavanserin (ACP-103) – more selective than AC-90179, orally active, antipsychotic in vivo, now FDA approved for the treatment of hallucinations and delusions associated with Parkinson's disease.[96][97][98][99][100]

Functional selectivity[szerkesztés]

5-HT2A-receptor ligands may differentially activate the transductional pathways (see above). Studies evaluated the activation of two effectors, PLC and PLA2, by means of their second messengers. Compounds displaying more pronounced functional selectivity are 2,5-DMA and 2C-N. The former induces IP accumulation without activating the PLA2 mediated response, while the latter elicits AA release without activating the PLC mediated response.[101]

Recent research has suggested potential signaling differences within the somatosensory cortex between 5-HT2A agonists that produce headshakes in the mouse and those that do not, such as lisuride, as these agents are also non-hallucinogenic in humans despite being active 5-HT2A agonists.[102][103] One known example of differences in signal transduction is between the two 5-HT2A agonists serotonin and DOI that involves differential recruitment of intracellular proteins called β-arrestins, more specifically arrestin beta 2.[104][105] Cyclopropylmethanamine derivatives such as (−)-19 have also been shown to act as 5-HT2A/2C agonists with functional selectivity for Gq-mediated signaling compared with β-arrestin recruitment.[106]

Genetics[szerkesztés]

Chromosome 13.

The 5-HT2A receptors is coded by the HTR2A gene. In humans the gene is located on chromosome 13. The gene has previously been called just HTR2 until the description of two related genes HTR2B and HTR2C. Several interesting polymorphisms have been identified for HTR2A: A-1438G (rs6311), C102T (rs6313) and His452Tyr (rs6314). Many more polymorphisms exist for the gene. A 2006 paper listed 255.[107][59]

Probable role in fibromyalgia as the T102C polymorphisms of the gene 5HT2A were common in fibromyalgia patients.[108]

Human HTR2A gene is thought to consist of 3 introns and 4 exons and to overlap with human gene HTR2A-AS1 which consists of 18 exons.[109] There are over 200 organisms that have orthologs with the human HTR2A. Currently, the best documented orthologs for HTR2A gene are the mouse,[110] and zebrafish.[111] There are 8 paralogs for the HTR2A gene. The HTR2A gene is known to interact and activate G-protein genes such as GNA14, GNAI1, GNAI3, GNAQ , and GNAZ.[112] These interactions are critical for cell signaling[113][114] and homeostasis [115] in many organisms.[116]

In human brain tissue, regulation of HTR2A varies depending on the region:[109] frontal cortex, amygdala, thalamus, brain stem and cerebellum. In a paper from 2016, they found that HTR2A undergoes a variety of different splicing events, including utilization of alternative splice acceptor sites, exon skipping, rare exon usage, and intron retention.[109]

Mechanisms of regulation[szerkesztés]

There are a few mechanisms of regulation for HTR2A gene such regulated by DNA methylation at particular transcript binding sites.[117][118] Another mechanism for the correct regulation of gene expression is achieved through alternative splicing. This is a co-transcriptional process, which allows the generation of multiple forms of mRNA transcript from a single coding unit and is emerging as an important control point for gene expression. In this process, exons or introns can be either included or excluded from precursor-mRNA resulting in multiple mature mRNA variants.[119] These mRNA variants result in different isoforms which may have antagonistic functions or differential expression patterns, yielding plasticity and adaptability to the cells.[120] One study found that the common genetic variant rs6311 regulates expression of HTR2A transcripts containing the extended 5' UTR.[109]

Associations with psychiatric disorders[szerkesztés]

Several studies have seen links between the -1438G/A polymorphism and mood disorders, such as bipolar disorder[121] and major depressive disorder.[122] A weak link with an odds ratio of 1.3 has been found between the T102C polymorphism and schizophrenia.[123] This polymorphism has also been studied in relation to suicide attempts, with a study finding excess of the C/C genotypes among the suicide attempters.[124] A number of other studies were devoted to finding an association of the gene with schizophrenia, with diverging results.[125]

These individual studies may, however, not give a full picture: A review from 2007 looking at the effect of different SNPs reported in separate studies stated that "genetic association studies [of HTR2A gene variants with psychiatric disorders] report conflicting and generally negative results" with no involvement, small or a not replicated role for the genetic variant of the gene.[126]

Polymorphisms in the promoter gene coding Early growth response 3 (EGR3) are associated with schizophrenia. Studies have demonstrated a relationship between EGR3 and HTR2A, and schizophrenia-like behaviors in transgenic animals.[127][128] Exactly how these results translate over to further biopsychological understanding of schizophrenia is still widely debated.[129][130] There is some evidence that dysfunction of HTR2A can impact pharmacological interventions.[131]

Several studies have assessed a relationship between 5-hydroxytryptamine (serotonin) 2A receptor (5-HTR2A) gene polymorphisms with an increased risk of suicidal behavior. One study revealed that T102C polymorphism is associated with suicidal behavior [132] but other studies failed to replicate these findings and found no association between polymorphism and suicidal behavior.[133]

Treatment response[szerkesztés]

Genetics seems also to be associated to some extent with the amount of adverse events in treatment of major depression disorder.[134]

Associations with substance abuse[szerkesztés]

Polymorphisms in the 5-HT2A receptor coding gene HTR2A (rs6313 and s6311) have been shown to have conflicting associations with alcohol misuse. For example, A polymorphism in the 5-HT2A receptor coding gene HTR2A (rs6313) was reported to predict lower positive alcohol expectancy, higher refusal self-efficacy, and lower alcohol misuse in a sample of 120 young adults. However, this polymorphism did not moderate the linkages between impulsivity, cognition, and alcohol misuse.[135] There are conflicting results as other studies have found associations between T102C polymorphisms alcohol misuse.[136][137]

Drug impact on gene expression[szerkesztés]

There is some evidence that methylation patterns may contribute to relapse behaviors in people who use stimulants.[138] In mice, psychotropic drugs such as DOI, LSD, DOM, and DOB which produced differing transcriptional patterns among several different brain regions.[128]

Methods to analyse the receptor[szerkesztés]

The receptor can be analysed by neuroimaging, radioligand, genetic analysis, measurements of ion flows, and in other ways.

Neuroimaging[szerkesztés]

The 5-HT2A receptors may be imaged with PET-scanners using the fluorine-18-altanserin,[139] MDL 100,907[140] or [11C]Cimbi-36[56][141] radioligands that binds to the neuroreceptor, e.g., one study reported a reduced binding of altanserin particularly in the hippocampus in patients with major depressive disorder.[142]

Altanserin uptake decreases with age reflecting a loss of specific 5-HT2A receptors with age.[143][144][145]

Other[szerkesztés]

Western blot with an affinity-purified antibody and examination of 5-HT2A receptor protein samples by electrophoresis has been described. Immunohistochemical staining of 5-HT2A receptors is also possible.[2]

References[szerkesztés]

  1. ↑ Cook EH, Fletcher KE, Wainwright M, Marks N, Yan SY, Leventhal BL (1994. augusztus 1.). „Primary structure of the human platelet serotonin 5-HT2A receptor: identify with frontal cortex serotonin 5-HT2A receptor”. Journal of Neurochemistry 63 (2), 465–469. o. DOI:10.1046/j.1471-4159.1994.63020465.x. PMID 8035173.  
  2. ↑ a b c Kling A. 5-HT2A: a serotonin receptor with a possible role in joint diseases. Umeå: Umeå Universitet (2013). ISBN 978-91-7459-549-9 
  3. ↑ Raote I. Serotonin 2A (5-HT2A) Receptor Function: Ligand-Dependent Mechanisms and Pathways, Ishier, Frontiers in Neuroscience. Press/Taylor & Francis (2007). ISBN 9780849339776 
  4. ↑ Martin P, Waters N, Schmidt CJ, Carlsson A, Carlsson ML (1998). „Rodent data and general hypothesis: antipsychotic action exerted through 5-HT2A receptor antagonism is dependent on increased serotonergic tone”. Journal of Neural Transmission 105 (4–5), 365–396. o. DOI:10.1007/s007020050064. PMID 9720968.  
  5. ↑ De Almeida RM, Rosa MM, Santos DM, Saft DM, Benini Q, Miczek KA (2006. május 1.). „5-HT(1B) receptors, ventral orbitofrontal cortex, and aggressive behavior in mice”. Psychopharmacology 185 (4), 441–450. o. DOI:10.1007/s00213-006-0333-3. PMID 16550387.  
  6. ↑ Eison AS, Mullins UL (1996). „Regulation of central 5-HT2A receptors: a review of in vivo studies”. Behavioural Brain Research 73 (1–2), 177–181. o. DOI:10.1016/0166-4328(96)00092-7. PMID 8788498.  
  7. ↑ a b Yadav PN, Kroeze WK, Farrell MS, Roth BL (2011. október 1.). „Antagonist functional selectivity: 5-HT2A serotonin receptor antagonists differentially regulate 5-HT2A receptor protein level in vivo”. The Journal of Pharmacology and Experimental Therapeutics 339 (1), 99–105. o. DOI:10.1124/jpet.111.183780. PMID 21737536.  
  8. ↑ Rinaldi-Carmona M, Congy C, Simiand J, Oury-Donat F, Soubrie P, Breliere JC, Le Fur G (1993. január 1.). „Repeated administration of SR 46349B, a selective 5-hydroxytryptamine2 antagonist, up-regulates 5-hydroxytryptamine2 receptors in mouse brain”. Molecular Pharmacology 43 (1), 84–89. o. PMID 8423772.  
  9. ↑ Gray JA, Roth BL (2001. november 1.). „Paradoxical trafficking and regulation of 5-HT(2A) receptors by agonists and antagonists”. Brain Research Bulletin 56 (5), 441–451. o. DOI:10.1016/s0361-9230(01)00623-2. PMID 11750789.  
  10. ↑ Vanover KE, Davis RE (2010. július 28.). „Role of 5-HT2A receptor antagonists in the treatment of insomnia”. Nature and Science of Sleep 2, 139–150. o. DOI:10.2147/nss.s6849. PMID 23616706.  
  11. ↑ Urban JD, Clarke WP, von Zastrow M, Nichols DE, Kobilka B, Weinstein H, Javitch JA, Roth BL, Christopoulos A, Sexton PM, Miller KJ, Spedding M, Mailman RB (2007. január 1.). „Functional selectivity and classical concepts of quantitative pharmacology”. The Journal of Pharmacology and Experimental Therapeutics 320 (1), 1–13. o. DOI:10.1124/jpet.106.104463. PMID 16803859.  
  12. ↑ Sanders-Bush E, Mayer SE. Chapter 11: 5-Hydroxytryptamine (Serotonin): Receptor Agonists and Antagonists, Goodman & Gilman's the Pharmacological Basis of Therapeutics, 11th, New York: McGraw-Hill (2006). ISBN 0-07-142280-3 
  13. ↑ Siegel GJ, Albers RW. Basic neurochemistry: molecular, cellular, and medical aspects, 7th, Academic Press, 241. o. (2005). ISBN 0-12-088397-X 
  14. ↑ Hoyer D, Hannon JP, Martin GR (2002. április 1.). „Molecular, pharmacological and functional diversity of 5-HT receptors”. Pharmacology, Biochemistry, and Behavior 71 (4), 533–554. o. DOI:10.1016/S0091-3057(01)00746-8. PMID 11888546.  
  15. ↑ (2017. január 4.) „A High-Resolution In Vivo Atlas of the Human Brain's Serotonin System” (angol nyelven). Journal of Neuroscience 37 (1), 120–128. o. DOI:10.1523/JNEUROSCI.2830-16.2016. ISSN 0270-6474. PMID 28053035.  
  16. ↑ Aghajanian GK, Marek GJ (1999. április 1.). „Serotonin, via 5-HT2A receptors, increases EPSCs in layer V pyramidal cells of prefrontal cortex by an asynchronous mode of glutamate release”. Brain Research 825 (1–2), 161–171. o. DOI:10.1016/S0006-8993(99)01224-X. PMID 10216183.  
  17. ↑ Marek GJ, Wright RA, Gewirtz JC, Schoepp DD (2001). „A major role for thalamocortical afferents in serotonergic hallucinogen receptor function in the rat neocortex”. Neuroscience 105 (2), 379–392. o. DOI:10.1016/S0306-4522(01)00199-3. PMID 11672605.  
  18. ↑ a b c Bortolozzi A, Díaz-Mataix L, Scorza MC, Celada P, Artigas F (2005. december 1.). „The activation of 5-HT receptors in prefrontal cortex enhances dopaminergic activity”. Journal of Neurochemistry 95 (6), 1597–1607. o. DOI:10.1111/j.1471-4159.2005.03485.x. PMID 16277612.  
  19. ↑ Amargós-Bosch M, Bortolozzi A, Puig MV, Serrats J, Adell A, Celada P, Toth M, Mengod G, Artigas F (2004. március 1.). „Co-expression and in vivo interaction of serotonin1A and serotonin2A receptors in pyramidal neurons of prefrontal cortex”. Cerebral Cortex 14 (3), 281–299. o. DOI:10.1093/cercor/bhg128. PMID 14754868.  
  20. ↑ Feng J, Cai X, Zhao J, Yan Z (2001. szeptember 1.). „Serotonin receptors modulate GABA(A) receptor channels through activation of anchored protein kinase C in prefrontal cortical neurons”. The Journal of Neuroscience 21 (17), 6502–6511. o. DOI:10.1523/JNEUROSCI.21-17-06502.2001. PMID 11517239.  
  21. ↑ Marek GJ (2009. június 1.). „Activation of adenosine(1) (A(1)) receptors suppresses head shakes induced by a serotonergic hallucinogen in rats”. Neuropharmacology 56 (8), 1082–1087. o. DOI:10.1016/j.neuropharm.2009.03.005. PMID 19324062.  
  22. ↑ Zhang C, Marek GJ (2008. január 1.). „AMPA receptor involvement in 5-hydroxytryptamine2A receptor-mediated pre-frontal cortical excitatory synaptic currents and DOI-induced head shakes”. Progress in Neuro-Psychopharmacology & Biological Psychiatry 32 (1), 62–71. o. DOI:10.1016/j.pnpbp.2007.07.009. PMID 17728034.  
  23. ↑ Gewirtz JC, Marek GJ (2000. november 1.). „Behavioral evidence for interactions between a hallucinogenic drug and group II metabotropic glutamate receptors”. Neuropsychopharmacology 23 (5), 569–576. o. DOI:10.1016/S0893-133X(00)00136-6. PMID 11027922.  
  24. ↑ Marek GJ, Zhang C (2008. szeptember 1.). „Activation of metabotropic glutamate 5 (mGlu5) receptors induces spontaneous excitatory synaptic currents in layer V pyramidal cells of the rat prefrontal cortex”. Neuroscience Letters 442 (3), 239–243. o. DOI:10.1016/j.neulet.2008.06.083. PMID 18621097.  
  25. ↑ Lambe EK, Liu RJ, Aghajanian GK (2007. november 1.). „Schizophrenia, hypocretin (orexin), and the thalamocortical activating system”. Schizophrenia Bulletin 33 (6), 1284–1290. o. DOI:10.1093/schbul/sbm088. PMID 17656637.  
  26. ↑ Liu RJ, Aghajanian GK (2008. január 1.). „Stress blunts serotonin- and hypocretin-evoked EPSCs in prefrontal cortex: role of corticosterone-mediated apical dendritic atrophy”. Proceedings of the National Academy of Sciences of the United States of America 105 (1), 359–364. o. DOI:10.1073/pnas.0706679105. PMID 18172209.  
  27. ↑ Geurts FJ, De Schutter E, Timmermans JP (2002. június 1.). „Localization of 5-HT2A, 5-HT3, 5-HT5A and 5-HT7 receptor-like immunoreactivity in the rat cerebellum”. Journal of Chemical Neuroanatomy 24 (1), 65–74. o. DOI:10.1016/S0891-0618(02)00020-0. PMID 12084412.  
  28. ↑ Maeshima T, Shutoh F, Hamada S, Senzaki K, Hamaguchi-Hamada K, Ito R, Okado N (1998. augusztus 1.). „Serotonin2A receptor-like immunoreactivity in rat cerebellar Purkinje cells”. Neuroscience Letters 252 (1), 72–74. o. DOI:10.1016/S0304-3940(98)00546-1. PMID 9756362.  
  29. ↑ Maeshima T, Shiga T, Ito R, Okado N (2004. december 1.). „Expression of serotonin2A receptors in Purkinje cells of the developing rat cerebellum”. Neuroscience Research 50 (4), 411–417. o. DOI:10.1016/j.neures.2004.08.010. PMID 15567478.  
  30. ↑ Dürk T, Panther E, Müller T, Sorichter S, Ferrari D, Pizzirani C, Di Virgilio F, Myrtek D, Norgauer J, Idzko M (2005. május 1.). „5-Hydroxytryptamine modulates cytokine and chemokine production in LPS-primed human monocytes via stimulation of different 5-HTR subtypes”. International Immunology 17 (5), 599–606. o. DOI:10.1093/intimm/dxh242. PMID 15802305.  
  31. ↑ Johansen A, Holm S, Dall B, Keller S, Kristensen JL, Knudsen GM, Hansen HD (2019. július 1.). „Human biodistribution and radiation dosimetry of the 5-HT2A receptor agonist Cimbi-36 labeled with carbon-11 in two positions”. EJNMMI Research 9 (1), 71. o. DOI:10.1186/s13550-019-0527-4. PMID 31367837.  
  32. ↑ a b Moreno JL, Holloway T, Albizu L, Sealfon SC, González-Maeso J (2011. április 1.). „Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists”. Neuroscience Letters 493 (3), 76–79. o. DOI:10.1016/j.neulet.2011.01.046. PMID 21276828.  
  33. ↑ a b Jalal B (2018. november 1.). „The neuropharmacology of sleep paralysis hallucinations: serotonin 2A activation and a novel therapeutic drug”. Psychopharmacology 235 (11), 3083–3091. o. DOI:10.1007/s00213-018-5042-1. PMID 30288594.  
  34. ↑ Yu B, Becnel J, Zerfaoui M, Rohatgi R, Boulares AH, Nichols CD (2008. november 1.). „Serotonin 5-hydroxytryptamine(2A) receptor activation suppresses tumor necrosis factor-alpha-induced inflammation with extraordinary potency”. The Journal of Pharmacology and Experimental Therapeutics 327 (2), 316–323. o. DOI:10.1124/jpet.108.143461. PMID 18708586.  
  35. ↑ Nau F, Yu B, Martin D, Nichols CD (2013). „Serotonin 5-HT2A receptor activation blocks TNF-α mediated inflammation in vivo”. PLOS ONE 8 (10), e75426. o. DOI:10.1371/journal.pone.0075426. PMID 24098382.  
  36. ↑ Van de Kar LD, Javed A, Zhang Y, Serres F, Raap DK, Gray TS (2001. május 1.). „5-HT2A receptors stimulate ACTH, corticosterone, oxytocin, renin, and prolactin release and activate hypothalamic CRF and oxytocin-expressing cells”. The Journal of Neuroscience 21 (10), 3572–3579. o. DOI:10.1523/JNEUROSCI.21-10-03572.2001. PMID 11331386.  
  37. ↑ Zhang Y, Damjanoska KJ, Carrasco GA, Dudas B, D'Souza DN, Tetzlaff J, Garcia F, Hanley NR, Scripathirathan K, Petersen BR, Gray TS, Battaglia G, Muma NA, Van de Kar LD (2002. november 1.). „Evidence that 5-HT2A receptors in the hypothalamic paraventricular nucleus mediate neuroendocrine responses to (−)DOI”. The Journal of Neuroscience 22 (21), 9635–9642. o. DOI:10.1523/JNEUROSCI.22-21-09635.2002. PMID 12417689.  
  38. ↑ Harvey JA (2003). „Role of the serotonin 5-HT(2A) receptor in learning”. Learning & Memory 10 (5), 355–362. o. DOI:10.1101/lm.60803. PMID 14557608.  
  39. ↑ Williams GV, Rao SG, Goldman-Rakic PS, Foresta M, Ropolo M, Degan P, Pettinati I, Kow YW, Damonte G, Poggi A, Frosina G (2010. március 1.). „Defective repair of 5-hydroxy-2'-deoxycytidine in Cockayne syndrome cells and its complementation by Escherichia coli formamidopyrimidine DNA glycosylase and endonuclease III”. Free Radical Biology & Medicine 48 (5), 681–690. o. DOI:10.1016/j.freeradbiomed.2009.12.007. PMID 11923449.  
  40. ↑ Passier A, van Puijenbroek E (2005. november 1.). „Mirtazapine-induced arthralgia”. British Journal of Clinical Pharmacology 60 (5), 570–572. o. DOI:10.1111/j.1365-2125.2005.02481.x. PMID 16236049.  
  41. ↑ Adwan MH (2016. augusztus 1.). „An update on drug-induced arthritis”. Rheumatology International 36 (8), 1089–1097. o. DOI:10.1007/s00296-016-3462-y. PMID 27000044.  
  42. ↑ Herth MM, Knudsen GM (2015. június 1.). „Current radiosynthesis strategies for 5-HT2A receptor PET tracers”. Journal of Labelled Compounds & Radiopharmaceuticals 58 (7), 265–273. o. DOI:10.1002/jlcr.3288. PMID 25997728.  
  43. ↑ Beer R: Anblick von toten Fliegen lässt Fliegen altern (német nyelven). science.ORF.at , 2023. június 13. (Hozzáférés: 2023. június 14.)
  44. ↑ Gendron CM, Chakraborty TS, Duran C, Dono T, Pletcher SD (2023. június 1.). „Ring neurons in the Drosophila central complex act as a rheostat for sensory modulation of aging”. PLOS Biology 21 (6), e3002149. o. DOI:10.1371/journal.pbio.3002149. PMID 37310911.  
  45. ↑ Nichols DE (2004. február 1.). „Hallucinogens”. Pharmacology & Therapeutics 101 (2), 131–181. o. DOI:10.1016/j.pharmthera.2003.11.002. PMID 14761703.  
  46. ↑ Blaazer AR, Smid P, Kruse CG (2008. szeptember 1.). „Structure-activity relationships of phenylalkylamines as agonist ligands for 5-HT(2A) receptors”. ChemMedChem 3 (9), 1299–1309. o. DOI:10.1002/cmdc.200800133. PMID 18666267.  
  47. ↑ Moreno JL, Muguruza C, Umali A, Mortillo S, Holloway T, Pilar-Cuéllar F, Mocci G, Seto J, Callado LF, Neve RL, Milligan G, Sealfon SC, López-Giménez JF, Meana JJ, Benson DL, González-Maeso J (2012. december 1.). „Identification of three residues essential for 5-hydroxytryptamine 2A-metabotropic glutamate 2 (5-HT2A·mGlu2) receptor heteromerization and its psychoactive behavioral function”. The Journal of Biological Chemistry 287 (53), 44301–44319. o. DOI:10.1074/jbc.M112.413161. PMID 23129762.  
  48. ↑ González-Maeso J, Ang RL, Yuen T, Chan P, Weisstaub NV, López-Giménez JF, Zhou M, Okawa Y, Callado LF, Milligan G, Gingrich JA, Filizola M, Meana JJ, Sealfon SC (2008. március 1.). „Identification of a serotonin/glutamate receptor complex implicated in psychosis”. Nature 452 (7183), 93–97. o. DOI:10.1038/nature06612. PMID 18297054.  
  49. ↑ Taddeucci A, Olivero G, Roggeri A, Milanese C, Giorgio FP, Grilli M, Marchi M, Garrone B, Pittaluga A (2022. szeptember 1.). „Presynaptic 5-HT2A-mGlu2/3 Receptor-Receptor Crosstalk in the Prefrontal Cortex: Metamodulation of Glutamate Exocytosis”. Cells 11 (19), 3035. o. DOI:10.3390/cells11193035. PMID 36230998.  
  50. ↑ Wingen M, Kuypers KP, Ramaekers JG (2007. február 1.). „The role of 5-HT1a and 5-HT2A receptors in attention and motor control: a mechanistic study in healthy volunteers”. Psychopharmacology 190 (3), 391–400. o. DOI:10.1007/s00213-006-0614-x. PMID 17124621.  
  51. ↑ Wingen M, Kuypers KP, Ramaekers JG (2007. július 1.). „Selective verbal and spatial memory impairment after 5-HT1A and 5-HT2A receptor blockade in healthy volunteers pre-treated with an SSRI”. Journal of Psychopharmacology 21 (5), 477–485. o. DOI:10.1177/0269881106072506. PMID 17092965.  
  52. ↑ Braden MR, Parrish JC, Naylor JC, Nichols DE (2006. december 1.). „Molecular interaction of serotonin 5-HT2A receptor residues Phe339(6.51) and Phe340(6.52) with superpotent N-benzyl phenethylamine agonists”. Molecular Pharmacology 70 (6), 1956–1964. o. DOI:10.1124/mol.106.028720. PMID 17000863.  
  53. ↑ Prabhakaran J, Solingapuram Sai KK, Zanderigo F, Rubin-Falcone H, Jorgensen MJ, Kaplan JR, Tooke KI, Mintz A, Mann JJ, Kumar JS (2017. január 1.). „In vivo evaluation of [18F]FECIMBI-36, an agonist 5-HT2A/2C receptor PET radioligand in nonhuman primate”. Bioorganic & Medicinal Chemistry Letters 27 (1), 21–23. o. DOI:10.1016/j.bmcl.2016.11.043. PMID 27889455.  
  54. ↑ McLean TH, Parrish JC, Braden MR, Marona-Lewicka D, Gallardo-Godoy A, Nichols DE (2006. szeptember 1.). „1-Aminomethylbenzocycloalkanes: conformationally restricted hallucinogenic phenethylamine analogues as functionally selective 5-HT2A receptor agonists”. Journal of Medicinal Chemistry 49 (19), 5794–5803. o. DOI:10.1021/jm060656o. PMID 16970404.  
  55. ↑ Ennis MD, Hoffman RL, Ghazal NB, Olson RM, Knauer CS, Chio CL, Hyslop DK, Campbell JE, Fitzgerald LW, Nichols NF, Svensson KA, McCall RB, Haber CL, Kagey ML, Dinh DM (2003. július 1.). „2,3,4,5-tetrahydro- and 2,3,4,5,11,11a-hexahydro-1H-[1,4]diazepino[1,7-a]indoles: new templates for 5-HT(2C) agonists”. Bioorganic & Medicinal Chemistry Letters 13 (14), 2369–2372. o. DOI:10.1016/S0960-894X(03)00403-7. PMID 12824036.  
  56. ↑ a b Ettrup A, da Cunha-Bang S, McMahon B, Lehel S, Dyssegaard A, Skibsted AW, Jørgensen LM, Hansen M, Baandrup AO, Bache S, Svarer C, Kristensen JL, Gillings N, Madsen J, Knudsen GM (2014. július 1.). „Serotonin 2A receptor agonist binding in the human brain with [¹¹C]Cimbi-36”. Journal of Cerebral Blood Flow and Metabolism 34 (7), 1188–1196. o. DOI:10.1038/jcbfm.2014.68. PMID 24780897.  
  57. ↑ Design and Synthesis of Selective Serotonin Receptor Agonists for Positron Emission Tomography Imaging of the Brain (Revised, Duplex print).pdf. Google Docs
  58. ↑ Dong C, Ly C, Dunlap LE, Vargas MV, Sun J, Hwang IW, Azinfar A, Oh WC, Wetsel WC, Olson DE, Tian L (2021. május 1.). „Psychedelic-inspired drug discovery using an engineered biosensor”. Cell 184 (10), 2779–2792.e18. o. DOI:10.1016/j.cell.2021.03.043. PMID 33915107.  
  59. ↑ a b Chambers JJ, Kurrasch-Orbaugh DM, Parker MA, Nichols DE (2001. március 1.). „Enantiospecific synthesis and pharmacological evaluation of a series of super-potent, conformationally restricted 5-HT(2A/2C) receptor agonists”. Journal of Medicinal Chemistry 44 (6), 1003–1010. o. DOI:10.1021/jm000491y. PMID 11300881.  
  60. ↑ Canal CE, Morgan D (2012. július 1.). „Head-twitch response in rodents induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine: a comprehensive history, a re-evaluation of mechanisms, and its utility as a model”. Drug Testing and Analysis 4 (7–8), 556–576. o. DOI:10.1002/dta.1333. PMID 22517680.  
  61. ↑ Gatch MB, Kozlenkov A, Huang RQ, Yang W, Nguyen JD, González-Maeso J, Rice KC, France CP, Dillon GH, Forster MJ, Schetz JA (2013. november 1.). „The HIV antiretroviral drug efavirenz has LSD-like properties”. Neuropsychopharmacology 38 (12), 2373–2384. o. DOI:10.1038/npp.2013.135. PMID 23702798.  
  62. ↑ Juncosa JI, Hansen M, Bonner LA, Cueva JP, Maglathlin R, McCorvy JD, Marona-Lewicka D, Lill MA, Nichols DE (2013. január 1.). „Extensive rigid analogue design maps the binding conformation of potent N-benzylphenethylamine 5-HT2A serotonin receptor agonist ligands”. ACS Chemical Neuroscience 4 (1), 96–109. o. DOI:10.1021/cn3000668. PMID 23336049.  
  63. ↑ Egan CT, Herrick-Davis K, Miller K, Glennon RA, Teitler M (1998. április 1.). „Agonist activity of LSD and lisuride at cloned 5HT2A and 5HT2C receptors”. Psychopharmacology 136 (4), 409–414. o. DOI:10.1007/s002130050585. PMID 9600588.  
  64. ↑ Hofmann C, Penner U, Dorow R, Pertz HH, Jähnichen S, Horowski R, Latté KP, Palla D, Schurad B (2006). „Lisuride, a dopamine receptor agonist with 5-HT2B receptor antagonist properties: absence of cardiac valvulopathy adverse drug reaction reports supports the concept of a crucial role for 5-HT2B receptor agonism in cardiac valvular fibrosis”. Clinical Neuropharmacology 29 (2), 80–86. o. DOI:10.1097/00002826-200603000-00005. PMID 16614540.  
  65. ↑ Janowsky A, Eshleman AJ, Johnson RA, Wolfrum KM, Hinrichs DJ, Yang J, Zabriskie TM, Smilkstein MJ, Riscoe MK (2014. július 1.). „Mefloquine and psychotomimetics share neurotransmitter receptor and transporter interactions in vitro”. Psychopharmacology 231 (14), 2771–2783. o. DOI:10.1007/s00213-014-3446-0. PMID 24488404.  
  66. ↑ de la Fuente Revenga M, Shah UH, Nassehi N, Jaster AM, Hemanth P, Sierra S, Dukat M, González-Maeso J (2021. március 1.). „Psychedelic-like Properties of Quipazine and Its Structural Analogues in Mice”. ACS Chemical Neuroscience 12 (5), 831–844. o. DOI:10.1021/acschemneuro.0c00291. PMID 33400504.  
  67. ↑ Åstrand A, Guerrieri D, Vikingsson S, Kronstrand R, Green H (2020. december 1.). „In vitro characterization of new psychoactive substances at the μ-opioid, CB1, 5HT1A, and 5-HT2A receptors-On-target receptor potency and efficacy, and off-target effects”. Forensic Science International 317, 110553. o. DOI:10.1016/j.forsciint.2020.110553. PMID 33160102.  
  68. ↑ Ennis MD, Hoffman RL, Ghazal NB, Olson RM, Knauer CS, Chio CL, Hyslop DK, Campbell JE, Fitzgerald LW, Nichols NF, Svensson KA, McCall RB, Haber CL, Kagey ML, Dinh DM (2003. július 1.). „2,3,4,5-tetrahydro- and 2,3,4,5,11,11a-hexahydro-1H-[1,4]diazepino[1,7-a]indoles: new templates for 5-HT(2C) agonists”. Bioorganic & Medicinal Chemistry Letters 13 (14), 2369–2372. o. DOI:10.1016/s0960-894x(03)00403-7. PMID 12824036.  
  69. ↑ Smith BM, Smith JM, Tsai JH, Schultz JA, Gilson CA, Estrada SA, Chen RR, Park DM, Prieto EB, Gallardo CS, Sengupta D, Thomsen WJ, Saldana HR, Whelan KT, Menzaghi F, Webb RR, Beeley NR (2005. március 1.). „Discovery and SAR of new benzazepines as potent and selective 5-HT(2C) receptor agonists for the treatment of obesity”. Bioorganic & Medicinal Chemistry Letters 15 (5), 1467–1470. o. DOI:10.1016/j.bmcl.2004.12.080. PMID 15713408.  
  70. ↑ Sablon:Cite patent
  71. ↑ Smith BM, Smith JM, Tsai JH, Schultz JA, Gilson CA, Estrada SA, Chen RR, Park DM, Prieto EB, Gallardo CS, Sengupta D, Dosa PI, Covel JA, Ren A, Webb RR, Beeley NR, Martin M, Morgan M, Espitia S, Saldana HR, Bjenning C, Whelan KT, Grottick AJ, Menzaghi F, Thomsen WJ (2008. január 1.). „Discovery and structure-activity relationship of (1R)-8-chloro-2,3,4,5-tetrahydro-1-methyl-1H-3-benzazepine (Lorcaserin), a selective serotonin 5-HT2C receptor agonist for the treatment of obesity”. Journal of Medicinal Chemistry 51 (2), 305–313. o. DOI:10.1021/jm0709034. PMID 18095642.  
  72. ↑ Jensen AA, Plath N, Pedersen MH, Isberg V, Krall J, Wellendorph P, Stensbøl TB, Gloriam DE, Krogsgaard-Larsen P, Frølund B (2013. február 1.). „Design, synthesis, and pharmacological characterization of N- and O-substituted 5,6,7,8-tetrahydro-4H-isoxazolo[4,5-d]azepin-3-ol analogues: novel 5-HT(2A)/5-HT(2C) receptor agonists with pro-cognitive properties”. Journal of Medicinal Chemistry 56 (3), 1211–1227. o. DOI:10.1021/jm301656h. PMID 23301527.  
  73. ↑ Cao D, Yu J, Wang H, Luo Z, Liu X, He L, Qi J, Fan L, Tang L, Chen Z, Li J, Cheng J, Wang S (2022. január 1.). „Structure-based discovery of nonhallucinogenic psychedelic analogs”. Science 375 (6579), 403–411. o. DOI:10.1126/science.abl8615. PMID 35084960.  
  74. ↑ Kaplan AL, Confair DN, Kim K, Barros-Álvarez X, Rodriguiz RM, Yang Y, Kweon OS, Che T, McCorvy JD, Kamber DN, Phelan JP, Martins LC, Pogorelov VM, DiBerto JF, Slocum ST, Huang XP, Kumar JM, Robertson MJ, Panova O, Seven AB, Wetsel AQ, Wetsel WC, Irwin JJ, Skiniotis G, Shoichet BK, Roth BL, Ellman JA (2022. október 1.). „Bespoke library docking for 5-HT2A receptor agonists with antidepressant activity”. Nature 610 (7932), 582–591. o. DOI:10.1038/s41586-022-05258-z. PMID 36171289.  
  75. ↑ Lyu J, Kapolka N, Gumpper R, Alon A, Wang L, Jain MK, Barros-Álvarez X, Sakamoto K, Kim Y, DiBerto J, Kim K, Tummino TA, Huang S, Irwin JJ, Tarkhanova OO, Moroz Y, Skiniotis G, Kruse AC, Shoichet BK, Roth BL (2023. december 1.). „AlphaFold2 structures template ligand discovery”. bioRxiv. DOI:10.1101/2023.12.20.572662. PMID 38187536.  
  76. ↑ Orr MJ, et al. Discovery of Highly Potent Serotonin 5-HT2 Receptor Agonists Inspired by Heteroyohimbine Natural Products. ACS Med. Chem. Lett. 2022; 13(4):648–657. doi:10.1021/acsmedchemlett.1c00694
  77. ↑ Sharif NA, McLaughlin MA, Kelly CR (2007. február 1.). „AL-34662: a potent, selective, and efficacious ocular hypotensive serotonin-2 receptor agonist”. Journal of Ocular Pharmacology and Therapeutics 23 (1), 1–13. o. DOI:10.1089/jop.2006.0093. PMID 17341144.  
  78. ↑ May JA, Dantanarayana AP, Zinke PW, McLaughlin MA, Sharif NA (2006. január 1.). „1-((S)-2-aminopropyl)-1H-indazol-6-ol: a potent peripherally acting 5-HT2 receptor agonist with ocular hypotensive activity”. Journal of Medicinal Chemistry 49 (1), 318–328. o. DOI:10.1021/jm050663x. PMID 16392816.  
  79. ↑ Marek GJ, Martin-Ruiz R, Abo A, Artigas F (2005. december 1.). „The selective 5-HT2A receptor antagonist M100907 enhances antidepressant-like behavioral effects of the SSRI fluoxetine”. Neuropsychopharmacology 30 (12), 2205–2215. o. DOI:10.1038/sj.npp.1300762. PMID 15886717.  
  80. ↑ Ishima T, Futamura T, Ohgi Y, Yoshimi N, Kikuchi T, Hashimoto K (2015. április 1.). „Potentiation of neurite outgrowth by brexpiprazole, a novel serotonin-dopamine activity modulator: a role for serotonin 5-HT1A and 5-HT2A receptors”. European Neuropsychopharmacology 25 (4), 505–511. o. DOI:10.1016/j.euroneuro.2015.01.014. PMID 25687838.  
  81. ↑ Das S, Barnwal P, Winston AB, Mondal S, Saha I (2016. február 1.). „Brexpiprazole: so far so good”. Therapeutic Advances in Psychopharmacology 6 (1), 39–54. o. DOI:10.1177/2045125315614739. PMID 26913177.  
  82. ↑ a b Pälvimäki EP, Roth BL, Majasuo H, Laakso A, Kuoppamäki M, Syvälahti E, Hietala J (1996. augusztus 1.). „Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2c receptor”. Psychopharmacology 126 (3), 234–240. o. DOI:10.1007/bf02246453. PMID 8876023.  
  83. ↑ Rang HP. Pharmacology. Edinburgh: Churchill Livingstone (2003). ISBN 0-443-07145-4  Page 187
  84. ↑ Shireman BT, Dvorak CA, Rudolph DA, Bonaventure P, Nepomuceno D, Dvorak L, Miller KL, Lovenberg TW, Carruthers NI (2008. március 1.). „2-Alkyl-4-aryl-pyrimidine fused heterocycles as selective 5-HT2A antagonists”. Bioorganic & Medicinal Chemistry Letters 18 (6), 2103–2108. o. DOI:10.1016/j.bmcl.2008.01.090. PMID 18282705.  
  85. ↑ Westkaemper RB, Runyon SP, Bondarev ML, Savage JE, Roth BL, Glennon RA (1999. szeptember 1.). „9-(Aminomethyl)-9,10-dihydroanthracene is a novel and unlikely 5-HT2A receptor antagonist”. European Journal of Pharmacology 380 (1), R5–R7. o. DOI:10.1016/S0014-2999(99)00525-7. PMID 10513561.  
  86. ↑ Westkaemper RB, Glennon RA (2002. június 1.). „Application of ligand SAR, receptor modeling and receptor mutagenesis to the discovery and development of a new class of 5-HT(2A) ligands”. Current Topics in Medicinal Chemistry 2 (6), 575–598. o. DOI:10.2174/1568026023393741. PMID 12052195.  
  87. ↑ Peddi S, Roth BL, Glennon RA, Westkaemper RB (2003. december 1.). „Spiro[9,10-dihydroanthracene]-9,3'-pyrrolidine-a structurally unique tetracyclic 5-HT2A receptor antagonist”. European Journal of Pharmacology 482 (1–3), 335–337. o. DOI:10.1016/j.ejphar.2003.09.059. PMID 14660041.  
  88. ↑ Runyon SP, Mosier PD, Roth BL, Glennon RA, Westkaemper RB (2008. november 1.). „Potential modes of interaction of 9-aminomethyl-9,10-dihydroanthracene (AMDA) derivatives with the 5-HT2A receptor: a ligand structure-affinity relationship, receptor mutagenesis and receptor modeling investigation”. Journal of Medicinal Chemistry 51 (21), 6808–6828. o. DOI:10.1021/jm800771x. PMID 18847250.  
  89. ↑ Wilson KJ, van Niel MB, Cooper L, Bloomfield D, O'Connor D, Fish LR, MacLeod AM (2007. május 1.). „2,5-Disubstituted pyridines: the discovery of a novel series of 5-HT2A ligands”. Bioorganic & Medicinal Chemistry Letters 17 (9), 2643–2648. o. DOI:10.1016/j.bmcl.2007.01.098. PMID 17314044.  
  90. ↑ a b Marcinkowska M, Kubacka M, Zagorska A, Jaromin A, Fajkis-Zajaczkowska N, Kolaczkowski M (2022. január 1.). „Exploring the antiplatelet activity of serotonin 5-HT2A receptor antagonists bearing 6-fluorobenzo[d]isoxazol-3-yl)propyl) motif- as potential therapeutic agents in the prevention of cardiovascular diseases”. Biomedicine & Pharmacotherapy 145, 112424. o. DOI:10.1016/j.biopha.2021.112424. PMID 34785417.  
  91. ↑ Nilsson T, Longmore J, Shaw D, Pantev E, Bard JA, Branchek T, Edvinsson L (1999. május 1.). „Characterisation of 5-HT receptors in human coronary arteries by molecular and pharmacological techniques”. European Journal of Pharmacology 372 (1), 49–56. o. DOI:10.1016/S0014-2999(99)00114-4. PMID 10374714.  
  92. ↑ Nagatomo T, Rashid M, Abul Muntasir H, Komiyama T (2004. október 1.). „Functions of 5-HT2A receptor and its antagonists in the cardiovascular system”. Pharmacology & Therapeutics 104 (1), 59–81. o. DOI:10.1016/j.pharmthera.2004.08.005. PMID 15500909.  
  93. ↑ Weiner DM, Burstein ES, Nash N, Croston GE, Currier EA, Vanover KE, Harvey SC, Donohue E, Hansen HC, Andersson CM, Spalding TA, Gibson DF, Krebs-Thomson K, Powell SB, Geyer MA, Hacksell U, Brann MR (2001. október 1.). „5-hydroxytryptamine2A receptor inverse agonists as antipsychotics”. The Journal of Pharmacology and Experimental Therapeutics 299 (1), 268–276. o. PMID 11561089.  
  94. ↑ Vanover KE, Harvey SC, Son T, Bradley SR, Kold H, Makhay M, Veinbergs I, Spalding TA, Weiner DM, Andersson CM, Tolf BR, Brann MR, Hacksell U, Davis RE (2004. szeptember 1.). „Pharmacological characterization of AC-90179 [2-(4-methoxyphenyl)-N-(4-methyl-benzyl)-N-(1-methyl-piperidin-4-yl)-acetamide hydrochloride]: a selective serotonin 2A receptor inverse agonist”. The Journal of Pharmacology and Experimental Therapeutics 310 (3), 943–951. o. DOI:10.1124/jpet.104.066688. PMID 15102927.  
  95. ↑ Rosenberg R, Seiden DJ, Hull SG, Erman M, Schwartz H, Anderson C, Prosser W, Shanahan W, Sanchez M, Chuang E, Roth T (2008. december 1.). „APD125, a selective serotonin 5-HT(2A) receptor inverse agonist, significantly improves sleep maintenance in primary insomnia”. Sleep 31 (12), 1663–1671. o. DOI:10.1093/sleep/31.12.1663. PMID 19090322.  
  96. ↑ Vanover KE, Weiner DM, Makhay M, Veinbergs I, Gardell LR, Lameh J, Del Tredici AL, Piu F, Schiffer HH, Ott TR, Burstein ES, Uldam AK, Thygesen MB, Schlienger N, Andersson CM, Son TY, Harvey SC, Powell SB, Geyer MA, Tolf BR, Brann MR, Davis RE (2006. május 1.). „Pharmacological and behavioral profile of N-(4-fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl) carbamide (2R,3R)-dihydroxybutanedioate (2:1) (ACP-103), a novel 5-hydroxytryptamine(2A) receptor inverse agonist”. The Journal of Pharmacology and Experimental Therapeutics 317 (2), 910–918. o. DOI:10.1124/jpet.105.097006. PMID 16469866.  
  97. ↑ Gardell LR, Vanover KE, Pounds L, Johnson RW, Barido R, Anderson GT, Veinbergs I, Dyssegaard A, Brunmark P, Tabatabaei A, Davis RE, Brann MR, Hacksell U, Bonhaus DW (2007. augusztus 1.). „ACP-103, a 5-hydroxytryptamine 2A receptor inverse agonist, improves the antipsychotic efficacy and side-effect profile of haloperidol and risperidone in experimental models”. The Journal of Pharmacology and Experimental Therapeutics 322 (2), 862–870. o. DOI:10.1124/jpet.107.121715. PMID 17519387.  
  98. ↑ Vanover KE, Betz AJ, Weber SM, Bibbiani F, Kielaite A, Weiner DM, Davis RE, Chase TN, Salamone JD (2008. október 1.). „A 5-HT2A receptor inverse agonist, ACP-103, reduces tremor in a rat model and levodopa-induced dyskinesias in a monkey model”. Pharmacology, Biochemistry, and Behavior 90 (4), 540–544. o. DOI:10.1016/j.pbb.2008.04.010. PMID 18534670.  
  99. ↑ Abbas A, Roth BL (2008. december 1.). „Pimavanserin tartrate: a 5-HT2A inverse agonist with potential for treating various neuropsychiatric disorders”. Expert Opinion on Pharmacotherapy 9 (18), 3251–3259. o. DOI:10.1517/14656560802532707. PMID 19040345.  
  100. ↑ Office of the Commissioner: FDA approves first drug to treat hallucinations and delusions associated with Parkinson's disease. FDA , 2019. szeptember 10.
  101. ↑ Moya PR, Berg KA, Gutiérrez-Hernandez MA, Sáez-Briones P, Reyes-Parada M, Cassels BK, Clarke WP (2007. június 1.). „Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors”. The Journal of Pharmacology and Experimental Therapeutics 321 (3), 1054–1061. o. DOI:10.1124/jpet.106.117507. PMID 17337633.  
  102. ↑ González-Maeso J, Weisstaub NV, Zhou M, Chan P, Ivic L, Ang R, Lira A, Bradley-Moore M, Ge Y, Zhou Q, Sealfon SC, Gingrich JA (2007. február 1.). „Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior”. Neuron 53 (3), 439–452. o. DOI:10.1016/j.neuron.2007.01.008. PMID 17270739.  
  103. ↑ Cussac D, Boutet-Robinet E, Ailhaud MC, Newman-Tancredi A, Martel JC, Danty N, Rauly-Lestienne I (2008. október 1.). „Agonist-directed trafficking of signalling at serotonin 5-HT2A, 5-HT2B and 5-HT2C-VSV receptors mediated Gq/11 activation and calcium mobilisation in CHO cells”. European Journal of Pharmacology 594 (1–3), 32–38. o. DOI:10.1016/j.ejphar.2008.07.040. PMID 18703043.  
  104. ↑ Schmid CL, Raehal KM, Bohn LM (2008. január 1.). „Agonist-directed signaling of the serotonin 2A receptor depends on beta-arrestin-2 interactions in vivo”. Proceedings of the National Academy of Sciences of the United States of America 105 (3), 1079–1084. o. DOI:10.1073/pnas.0708862105. PMID 18195357.  
  105. ↑ Abbas A, Roth BL (2008. január 1.). „Arresting serotonin”. Proceedings of the National Academy of Sciences of the United States of America 105 (3), 831–832. o. DOI:10.1073/pnas.0711335105. PMID 18195368.  
  106. ↑ Zhang G, Cheng J, McCorvy JD, Lorello PJ, Caldarone BJ, Roth BL, Kozikowski AP (2017. július 1.). „Discovery of N-Substituted (2-Phenylcyclopropyl)methylamines as Functionally Selective Serotonin 2C Receptor Agonists for Potential Use as Antipsychotic Medications”. Journal of Medicinal Chemistry 60 (14), 6273–6288. o. DOI:10.1021/acs.jmedchem.7b00584. PMID 28657744.  
  107. ↑ Bonis J, Furlong LI, Sanz F (2006. október 1.). „OSIRIS: a tool for retrieving literature about sequence variants”. Bioinformatics 22 (20), 2567–2569. o. DOI:10.1093/bioinformatics/btl421. PMID 16882651. „Supplementary material to article” 
  108. ↑ Goldstein AT, Pukall C, Goldstein IL. Fibromyalgia and Female Sexual Pain Disorders, Female Sexual Pain Disorders: Evaluation and Management, 2, Wiley (2020). ISBN 978-1119482666 
  109. ↑ a b c d Ruble CL, Smith RM, Calley J, Munsie L, Airey DC, Gao Y, Shin JH, Hyde TM, Straub RE, Weinberger DR, Nisenbaum LK (2016. január 1.). „Genomic structure and expression of the human serotonin 2A receptor gene (HTR2A) locus: identification of novel HTR2A and antisense (HTR2A-AS1) exons”. BMC Genetics 17 (1), 16. o. DOI:10.1186/s12863-015-0325-6. PMID 26738766.  
  110. ↑ Medrihan L, Sagi Y, Inde Z, Krupa O, Daniels C, Peyrache A, Greengard P (2017. augusztus 1.). „Initiation of Behavioral Response to Antidepressants by Cholecystokinin Neurons of the Dentate Gyrus”. Neuron 95 (3), 564–576.e4. o. DOI:10.1016/j.neuron.2017.06.044. PMID 28735749.  
  111. ↑ Griffin A, Hamling KR, Knupp K, Hong S, Lee LP, Baraban SC (2017. március 1.). „Clemizole and modulators of serotonin signalling suppress seizures in Dravet syndrome”. Brain 140 (3), 669–683. o. DOI:10.1093/brain/aww342. PMID 28073790.  
  112. ↑ Giulietti M, Vivenzio V, Piva F, Principato G, Bellantuono C, Nardi B (2014. július 1.). „How much do we know about the coupling of G-proteins to serotonin receptors?”. Molecular Brain 7 (1), 49. o. DOI:10.1186/s13041-014-0049-y. PMID 25011628.  
  113. ↑ Lal D, May P, Perez-Palma E, Samocha KE, Kosmicki JA, Robinson EB, Møller RS, Krause R, Nürnberg P, Weckhuysen S, De Jonghe P, Guerrini R, Niestroj LM, Du J, Marini C, Ware JS, Kurki M, Gormley P, Tang S, Wu S, Biskup S, Poduri A, Neubauer BA, Koeleman BP, Helbig KL, Weber YG, Helbig I, Majithia AR, Palotie A, Daly MJ (2020. március 1.). „Gene family information facilitates variant interpretation and identification of disease-associated genes in neurodevelopmental disorders”. Genome Medicine 12 (1), 28. o. DOI:10.1186/s13073-020-00725-6. PMID 32183904.  
  114. ↑ Gao W, Guo N, Zhao S, Chen Z, Zhang W, Yan F, Liao H, Chi K (2020. november 1.). „HTR2A promotes the development of cardiac hypertrophy by activating PI3K-PDK1-AKT-mTOR signaling”. Cell Stress & Chaperones 25 (6), 899–908. o. DOI:10.1007/s12192-020-01124-x. PMID 32519137.  
  115. ↑ Cao X, Wang Y, Shu D, Qu H, Luo C, Hu X (2020. október 1.). „Food intake-related genes in chicken determined through combinatorial genome-wide association study and transcriptome analysis”. Animal Genetics 51 (5), 741–751. o. DOI:10.1111/age.12980. PMID 32720725.  
  116. ↑ Garza-Brenner E, Sifuentes-Rincón AM, Randel RD, Paredes-Sánchez FA, Parra-Bracamonte GM, Arellano Vera W, Rodríguez Almeida FA, Segura Cabrera A (2017. augusztus 1.). „Association of SNPs in dopamine and serotonin pathway genes and their interacting genes with temperament traits in Charolais cows”. Journal of Applied Genetics 58 (3), 363–371. o. DOI:10.1007/s13353-016-0383-0. PMID 27987181.  
  117. ↑ Cheah SY, Lawford BR, Young RM, Morris CP, Voisey J (2017. január 1.). „mRNA Expression and DNA Methylation Analysis of Serotonin Receptor 2A (HTR2A) in the Human Schizophrenic Brain”. Genes 8 (1), 14. o. DOI:10.3390/genes8010014. PMID 28054990.  
  118. ↑ Falkenberg VR, Gurbaxani BM, Unger ER, Rajeevan MS (2011. március 1.). „Functional genomics of serotonin receptor 2A (HTR2A): interaction of polymorphism, methylation, expression and disease association”. Neuromolecular Medicine 13 (1), 66–76. o. DOI:10.1007/s12017-010-8138-2. PMID 20941551.  
  119. ↑ Kelemen O, Convertini P, Zhang Z, Wen Y, Shen M, Falaleeva M, Stamm S (2013. február 1.). „Function of alternative splicing”. Gene 514 (1), 1–30. o. DOI:10.1016/j.gene.2012.07.083. PMID 22909801.  
  120. ↑ Wang ET, Ward AJ, Cherone JM, Giudice J, Wang TT, Treacy DJ, Lambert NJ, Freese P, Saxena T, Cooper TA, Burge CB (2015. június 1.). „Antagonistic regulation of mRNA expression and splicing by CELF and MBNL proteins”. Genome Research 25 (6), 858–871. o. DOI:10.1101/gr.184390.114. PMID 25883322.  
  121. ↑ Chee IS, Lee SW, Kim JL, Wang SK, Shin YO, Shin SC, Lee YH, Hwang HM, Lim MR (2001. szeptember 1.). „5-HT2A receptor gene promoter polymorphism -1438A/G and bipolar disorder”. Psychiatric Genetics 11 (3), 111–114. o. DOI:10.1097/00041444-200109000-00001. PMID 11702051.  
  122. ↑ Choi MJ, Lee HJ, Lee HJ, Ham BJ, Cha JH, Ryu SH, Lee MS (2004). „Association between major depressive disorder and the -1438A/G polymorphism of the serotonin 2A receptor gene”. Neuropsychobiology 49 (1), 38–41. o. DOI:10.1159/000075337. PMID 14730199.  
  123. ↑ Williams J, Spurlock G, McGuffin P, Mallet J, Nöthen MM, Gill M, Aschauer H, Nylander PO, Macciardi F, Owen MJ (1996. május 1.). „Association between schizophrenia and T102C polymorphism of the 5-hydroxytryptamine type 2a-receptor gene. European Multicentre Association Study of Schizophrenia (EMASS) Group”. Lancet 347 (9011), 1294–1296. o. DOI:10.1016/s0140-6736(96)90939-3. PMID 8622505.  
  124. ↑ Vaquero-Lorenzo C, Baca-Garcia E, Diaz-Hernandez M, Perez-Rodriguez MM, Fernandez-Navarro P, Giner L, Carballo JJ, Saiz-Ruiz J, Fernandez-Piqueras J, Baldomero EB, de Leon J, Oquendo MA (2008. július 1.). „Association study of two polymorphisms of the serotonin-2A receptor gene and suicide attempts”. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 147B (5), 645–649. o. DOI:10.1002/ajmg.b.30642. PMID 18163387.  
  125. ↑ Gene Overview of All Published Schizophrenia-Association Studies for HTR2A Archiválva 2009. február 21-i dátummal a Wayback Machine-ben. – SzGene database at Schizophrenia Research Forum.
  126. ↑ Serretti A, Drago A, De Ronchi D (2007). „HTR2A gene variants and psychiatric disorders: a review of current literature and selection of SNPs for future studies”. Current Medicinal Chemistry 14 (19), 2053–2069. o. DOI:10.2174/092986707781368450. PMID 17691947.  
  127. ↑ Maple AM, Zhao X, Elizalde DI, McBride AK, Gallitano AL (2015. július 1.). „Htr2a Expression Responds Rapidly to Environmental Stimuli in an Egr3-Dependent Manner”. ACS Chemical Neuroscience 6 (7), 1137–1142. o. DOI:10.1021/acschemneuro.5b00031. PMID 25857407.  
  128. ↑ a b Williams AA, Ingram WM, Levine S, Resnik J, Kamel CM, Lish JR, Elizalde DI, Janowski SA, Shoker J, Kozlenkov A, González-Maeso J, Gallitano AL (2012. szeptember 1.). „Reduced levels of serotonin 2A receptors underlie resistance of Egr3-deficient mice to locomotor suppression by clozapine”. Neuropsychopharmacology 37 (10), 2285–2298. o. DOI:10.1038/npp.2012.81. PMID 22692564.  
  129. ↑ Latorre E, Mesonero JE, Harries LW (2019. november 1.). „Alternative splicing in serotonergic system: Implications in neuropsychiatric disorders”. Journal of Psychopharmacology 33 (11), 1352–1363. o. DOI:10.1177/0269881119856546. PMID 31210090.  
  130. ↑ Spies M, Nasser A, Ozenne B, Jensen PS, Knudsen GM, Fisher PM (2020. november 1.). „Common HTR2A variants and 5-HTTLPR are not associated with human in vivo serotonin 2A receptor levels”. Human Brain Mapping 41 (16), 4518–4528. o. DOI:10.1002/hbm.25138. PMID 32697408.  
  131. ↑ Qesseveur G, Petit AC, Nguyen HT, Dahan L, Colle R, Rotenberg S, Seif I, Robert P, David D, Guilloux JP, Gardier AM, Verstuyft C, Becquemont L, Corruble E, Guiard BP (2016. június 1.). „Genetic dysfunction of serotonin 2A receptor hampers response to antidepressant drugs: A translational approach”. Neuropharmacology 105, 142–153. o. DOI:10.1016/j.neuropharm.2015.12.022. PMID 26764241.  
  132. ↑ Ghasemi A, Seifi M, Baybordi F, Danaei N, Samadi Rad B (2018. június 1.). „Association between serotonin 2A receptor genetic variations, stressful life events and suicide”. Gene 658, 191–197. o. DOI:10.1016/j.gene.2018.03.023. PMID 29526601.  
  133. ↑ Videtic A, Pungercic G, Pajnic IZ, Zupanc T, Balazic J, Tomori M, Komel R (2006. szeptember 1.). „Association study of seven polymorphisms in four serotonin receptor genes on suicide victims”. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 141B (6), 669–672. o. DOI:10.1002/ajmg.b.30390. PMID 16856120.  
  134. ↑ Laje G, McMahon FJ (2007. december 1.). „The pharmacogenetics of major depression: past, present, and future”. Biological Psychiatry 62 (11), 1205–1207. o. DOI:10.1016/j.biopsych.2007.09.016. PMID 17949692.  
  135. ↑ Leamy TE, Connor JP, Voisey J, Young RM, Gullo MJ (2016. december 1.). „Alcohol misuse in emerging adulthood: Association of dopamine and serotonin receptor genes with impulsivity-related cognition”. Addictive Behaviors 63, 29–36. o. DOI:10.1016/j.addbeh.2016.05.008. PMID 27399274.  
  136. ↑ Jakubczyk A, Wrzosek M, Lukaszkiewicz J, Sadowska-Mazuryk J, Matsumoto H, Sliwerska E, Glass J, Burmeister M, Brower KJ, Wojnar M (2012. január 1.). „The CC genotype in HTR2A T102C polymorphism is associated with behavioral impulsivity in alcohol-dependent patients”. Journal of Psychiatric Research 46 (1), 44–49. o. DOI:10.1016/j.jpsychires.2011.09.001. PMID 21930285.  
  137. ↑ da Silva Junior FC, Araujo RM, Sarmento AS, de Carvalho MM, Fernandes HF, Yoshioka FK, Pinto GR, Motta FJ, Canalle R (2020. december 1.). „The association of A-1438G and T102C polymorphisms in HTR2A and 120 bp duplication in DRD4 with alcoholic dependence in a northeastern Brazilian male population”. Gene Reports 21, 100889. o. DOI:10.1016/j.genrep.2020.100889.  
  138. ↑ Land MA, Ramesh D, Miller AL, Pyles RB, Cunningham KA, Moeller FG, Anastasio NC (2020. június 10.). „Methylation Patterns of the HTR2A Associate With Relapse-Related Behaviors in Cocaine-Dependent Participants”. Frontiers in Psychiatry 11, 532. o. DOI:10.3389/fpsyt.2020.00532. PMID 32587535.  
  139. ↑ Lemaire C, Cantineau R, Guillaume M, Plenevaux A, Christiaens L (1991. december 1.). „Fluorine-18-altanserin: a radioligand for the study of serotonin receptors with PET: radiolabeling and in vivo biologic behavior in rats”. Journal of Nuclear Medicine 32 (12), 2266–2272. o. PMID 1744713.  
  140. ↑ Lundkvist C, Halldin C, Ginovart N, Nyberg S, Swahn CG, Carr AA, Brunner F, Farde L (1996). „[11C]MDL 100907, a radioligland for selective imaging of 5-HT(2A) receptors with positron emission tomography”. Life Sciences 58 (10), PL 187-PL 192. o. DOI:10.1016/0024-3205(96)00013-6. PMID 8602111.  
  141. ↑ Johansen A, Hansen HD, Svarer C, Lehel S, Leth-Petersen S, Kristensen JL, Gillings N, Knudsen GM (2018. április 1.). „The importance of small polar radiometabolites in molecular neuroimaging: A PET study with [11C]Cimbi-36 labeled in two positions”. Journal of Cerebral Blood Flow and Metabolism 38 (4), 659–668. o. DOI:10.1177/0271678x17746179. PMID 29215308.  
  142. ↑ Mintun MA, Sheline YI, Moerlein SM, Vlassenko AG, Huang Y, Snyder AZ (2004. február 1.). „Decreased hippocampal 5-HT2A receptor binding in major depressive disorder: in vivo measurement with [18F]altanserin positron emission tomography”. Biological Psychiatry 55 (3), 217–224. o. DOI:10.1016/j.biopsych.2003.08.015. PMID 14744461.  
  143. ↑ Rosier A, Dupont P, Peuskens J, Bormans G, Vandenberghe R, Maes M, de Groot T, Schiepers C, Verbruggen A, Mortelmans L (1996. november 1.). „Visualisation of loss of 5-HT2A receptors with age in healthy volunteers using [18F]altanserin and positron emission tomographic imaging”. Psychiatry Research 68 (1), 11–22. o. DOI:10.1016/S0925-4927(96)02806-5. PMID 9027929.  
  144. ↑ Meltzer CC, Smith G, Price JC, Reynolds CF, Mathis CA, Greer P, Lopresti B, Mintun MA, Pollock BG, Ben-Eliezer D, Cantwell MN, Kaye W, DeKosky ST (1998. november 1.). „Reduced binding of [18F]altanserin to serotonin type 2A receptors in aging: persistence of effect after partial volume correction”. Brain Research 813 (1), 167–171. o. DOI:10.1016/S0006-8993(98)00909-3. PMID 9824691.  
  145. ↑ Adams KH, Pinborg LH, Svarer C, Hasselbalch SG, Holm S, Haugbøl S, Madsen K, Frøkjaer V, Martiny L, Paulson OB, Knudsen GM (2004. március 1.). „A database of [(18)F]-altanserin binding to 5-HT(2A) receptors in normal volunteers: normative data and relationship to physiological and demographic variables”. NeuroImage 21 (3), 1105–1113. o. DOI:10.1016/j.neuroimage.2003.10.046. PMID 15006678.  

További információk[szerkesztés]

  • Perez-Aguilar JM, Shan J, LeVine MV, Khelashvili G, Weinstein H (2014. november 1.). „A functional selectivity mechanism at the serotonin-2A GPCR involves ligand-dependent conformations of intracellular loop 2”. Journal of the American Chemical Society 136 (45), 16044–16054. o. DOI:10.1021/ja508394x. PMID 25314362.  
  • 5-HT2A. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology
  • 5-HT2A+Receptor a U.S. National Library of Medicine Medical Subject Headings (MeSH) honlapján
  • Humán HTR2A genombeli helye és HTR2A géninformációs lap a UCSC Genome Browserben.
  • Sablon:PDBe-KB2
A lap eredeti címe: „https://hu.wikipedia.org/w/index.php?title=Szerkesztő:Alfa-ketosav/5-HT2A-receptor&oldid=27145740”