Like all 5-HT2 receptors, the 5-HT2A receptor is Gq/G11-protein coupled. This is the main excitatory receptor subtype among the GPCRs for serotonin, although 5-HT2A may also have an inhibitory effect[7] on certain areas such as the visual cortex and the orbitofrontal cortex.[8] This receptor was first noted for its importance as a target of serotonergic psychedelic drugs such as LSD and psilocybin mushrooms. Later it came back to prominence because it was also found to be mediating, at least partly, the action of many antipsychotic drugs, especially atypical antipsychotics.
Downregulation of post-synaptic 5-HT2A receptor is an adaptive process provoked by chronic administration of selective serotonin reuptake inhibitors (SSRIs) and atypical antipsychotics. Suicidal and otherwise depressed patients have had more 5-HT2A receptors than normal patients. These findings suggest that post-synaptic 5-HT2A overdensity is involved in the pathogenesis of depression.[9]
Paradoxical down-regulation of 5-HT2A receptors can be observed with several 5-HT2A antagonists.[10] 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.[10][11] Additionally, a couple of other antagonists may have no effect on 5-HT2A receptor number.[12] 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.[13]
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.[14]
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.[15] 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.[16] 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.[17]
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.[33] 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.[34]
Physiological processes mediated by the receptor include:
CNS: neuronal excitation, hallucinations, out-of-body experiences, and fear. Primarily responsible for the psychedelic effects associated with 5-HT2A receptor agonists such as LSD, DMT, etc.[35][36]
Activation of the 5-HT2Areceptor 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.[48][49] 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.[50][51][35] However, newer research suggests that 5HT2A and mGlu2 receptors do not physically associate with each other, so the former findings have questionable relevance.[52] Agonists enhance dopamine in PFC,[21] enhance memory and play an active role in attention and learning.[53][54]
(R)-DOI– traditionally the most common 5-HT2A reference agonist used in research[65]
Efavirenz– an antiretroviral drug, produces psychiatric side effects thought to be mediated by 5-HT2A.[66]
DMBMPP– a structurally constrained derivative of 25B-NBOMe, which acts as a potent partial agonist with 124× selectivity for 5-HT2A over 5-HT2C, making it the most selective agonist ligand identified to date.[67]
Mefloquine– an antimalarial drug, also produces psychiatric side effects which may be mediated through 5-HT2A and/or 5-HT2C receptors.[70]
Methysergide– a congener of methylergonovine, used in treatment of migraine blocks 5-HT2A and 5-HT2C receptors, but sometimes acts as partial agonist, in some preparations.
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.[91] Animal studies with this compound showed it to be free of hallucinogenic effects at doses up to 30mg/kg, although several of its more lipophilic analogues did produce the head-twitch response known to be characteristic of hallucinogenic effects in rodents.[92]
Antagonists
Volinanserin (MDL100907, M100907)– the most potent 5-HT2A antagonist.[93] It underwent a few clinical trials but never got marketed.
Trazodone– a potent 5-HT2A antagonist, as well as an antagonist on other serotonin receptors.
Cyclobenzaprine– a strong antagonist of both 5-HT2A and 5-HT2C receptors
Although ergot alkaloids are mostly nonspecific 5-HT receptor antagonists, a few ergot derivatives such as metergoline and nicergoline bind preferentially to members of the 5-HT2 receptor family.
The discovery of ketanserin was a landmark in the pharmacology of 5-HT2 receptors. Ketanserin, though capable of blocking 5-HT induced platelet adhesion, however does not mediate its well-known antihypertensive action through 5-HT2 receptor family, but through its high affinity for alpha1 adrenergic receptors. It also has high affinity for H1 histaminergic receptors equal to that at 5-HT2A receptors. Compounds chemically related to ketanserin such as ritanserin are more selective 5-HT2A receptor antagonists with low affinity for alpha-adrenergic receptors. However, ritanserin, like most other 5-HT2A receptor antagonists, also potently inhibits 5-HT2C receptors.
Antagonists and cardiovascular disease
Increased 5-HT2A expression is observed in patients with coronary thrombosis, and the receptor has been associated with processes that influence atherosclerosis.[104] As the receptor is present in coronary arteries[105] and capable of mediating vasoconstriction, 5-HT2A has also been linked to coronary artery spasms.[106] 5-HT antagonism, therefore, has potential in the prevention of cardiovascular disease, however, no studies have been published so far.[104]
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.[109]
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.[110][111][112][113][114]
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.[116][117]
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.[118][119] 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.[120]
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.[121][64]
Probable role in fibromyalgia as the T102C polymorphisms of the gene 5HT2A were common in fibromyalgia patients.[122]
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.[123] There are over 200 organisms that have orthologs with the human HTR2A. Currently, the best documented orthologs for HTR2A gene are the mouse,[124] and zebrafish.[125] 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.[126] These interactions are critical for cell signaling[127][128] and homeostasis [129] in many organisms.[130]
There are a few mechanisms of regulation for HTR2A gene such regulated by DNA methylation at particular transcript binding sites.[131][132] 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.[133] These mRNA variants result in different isoforms which may have antagonistic functions or differential expression patterns, yielding plasticity and adaptability to the cells.[134] One study found that the common genetic variant rs6311 regulates expression of HTR2A transcripts containing the extended 5' UTR.[123]
Associations with psychiatric disorders
Several studies have seen links between the -1438G/A polymorphism and mood disorders, such as major depressive disorder.[135]
and a strong link with an odds ratio of 1.3 has been found between the T102C polymorphism and schizophrenia.[136]
This polymorphism has also been studied in relation to suicide attempts, with a study finding excess of the G/G and G/A genotypes among the suicide attempters.[137] A number of other studies were devoted to finding an association of the gene with schizophrenia, with diverging results.[138]
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.[139]
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.[140][141] Exactly how these results translate over to further biopsychological understanding of schizophrenia is still widely debated.[142][143] There is some evidence that dysfunction of HTR2A can impact pharmacological interventions.[144]
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 [145] but other studies failed to replicate these findings and found no association between polymorphism and suicidal behavior.[146]
Treatment response
Genetics seems also to be associated to some extent with the amount of adverse events in treatment of major depression disorder.[147]
Associations with substance abuse
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.[148] There are conflicting results as other studies have found associations between T102C polymorphisms alcohol misuse.[149][150]
Drug impact on gene expression
There is some evidence that methylation patterns may contribute to relapse behaviors in people who use stimulants.[151] In mice, psychotropic drugs such as DOI, LSD, DOM, and DOB which produced differing transcriptional patterns among several different brain regions.[141]
The receptor can be analysed by neuroimaging, radioligand, genetic analysis, measurements of ion flows, and in other ways.
Altanserin uptake decreases with age reflecting a loss of specific 5-HT2A receptors with age.[156][157][158]
Other
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.[5]
Cook EH, Fletcher KE, Wainwright M, Marks N, Yan SY, Leventhal BL (August 1994). "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. doi:10.1046/j.1471-4159.1994.63020465.x. PMID8035173. S2CID40207336.
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. doi:10.1007/s007020050064. PMID9720968. S2CID20944107.
De Almeida RM, Rosa MM, Santos DM, Saft DM, Benini Q, Miczek KA (May 2006). "5-HT(1B) receptors, ventral orbitofrontal cortex, and aggressive behavior in mice". Psychopharmacology. 185 (4): 441–450. doi:10.1007/s00213-006-0333-3. PMID16550387. S2CID33274637.
Sanders-Bush E, Mayer SE (2006). "Chapter 11: 5-Hydroxytryptamine (Serotonin): Receptor Agonists and Antagonists". In Brunton LL, Lazo JS, Parker K (eds.). Goodman & Gilman's the Pharmacological Basis of Therapeutics (11thed.). New York: McGraw-Hill. ISBN0-07-142280-3.
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. doi:10.1016/S0306-4522(01)00199-3. PMID11672605. S2CID19764312.
Geurts FJ, De Schutter E, Timmermans JP (June 2002). "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. doi:10.1016/S0891-0618(02)00020-0. PMID12084412. S2CID16510169.
Maeshima T, Shiga T, Ito R, Okado N (December 2004). "Expression of serotonin2A receptors in Purkinje cells of the developing rat cerebellum". Neuroscience Research. 50 (4): 411–417. doi:10.1016/j.neures.2004.08.010. PMID15567478. S2CID5772490.
Wingen M, Kuypers KP, Ramaekers JG (February 2007). "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. doi:10.1007/s00213-006-0614-x. PMID17124621. S2CID25125461.
Wingen M, Kuypers KP, Ramaekers JG (July 2007). "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. doi:10.1177/0269881106072506. PMID17092965. S2CID19575488.
Chambers JJ, Kurrasch-Orbaugh DM, Parker MA, Nichols DE (March 2001). "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. doi:10.1021/jm000491y. PMID11300881.
Hofmann C, Penner U, Dorow R, Pertz HH, Jähnichen S, Horowski R, etal. (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. doi:10.1097/00002826-200603000-00005. PMID16614540. S2CID33849447.
Smith BM, Smith JM, Tsai JH, Schultz JA, Gilson CA, Estrada SA, etal. (March 2005). "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. doi:10.1016/j.bmcl.2004.12.080. PMID15713408.
WO WO2007149728,Mohapatra S, Hellberg MR, Feng Z,"Aryl and heteroaryl tetrahydrobenzazepine derivatives and their use for treating glaucoma", assigned to Alcon Manufacturing, Ltd.
Smith BM, Smith JM, Tsai JH, Schultz JA, Gilson CA, Estrada SA, etal. (January 2008). "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. doi:10.1021/jm0709034. PMID18095642.
Märcher Rørsted E, Jensen AA, Kristensen JL (November 2021). "25CN-NBOH: A Selective Agonist for in vitro and in vivo Investigations of the Serotonin 2A Receptor". ChemMedChem. 16 (21): 3263–3270. doi:10.1002/cmdc.202100395. PMID34288515.
Jensen AA, Cecchi CR, Hibicke M, Bach AH, Kaadt E, Marcher-Rorsted E, etal. (22 April 2024). "The selective 5-HT 2A receptor agonist LPH-5 induces persistent and robust antidepressant-like effects in rodents". bioRxiv. doi:10.1101/2024.04.19.590212.
Yuan H, Guo Z, Luo T (February 2017). "Synthesis of (+)-Lysergol and Its Analogues To Assess Serotonin Receptor Activity". Org Lett. 19 (3): 624–627. doi:10.1021/acs.orglett.6b03779. PMID28106398.
Westkaemper RB, Runyon SP, Bondarev ML, Savage JE, Roth BL, Glennon RA (September 1999). "9-(Aminomethyl)-9,10-dihydroanthracene is a novel and unlikely 5-HT2A receptor antagonist". European Journal of Pharmacology. 380 (1): R5–R7. doi:10.1016/S0014-2999(99)00525-7. PMID10513561.
Westkaemper RB, Glennon RA (June 2002). "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. doi:10.2174/1568026023393741. PMID12052195. S2CID23576058.
Wilson KJ, van Niel MB, Cooper L, Bloomfield D, O'Connor D, Fish LR, etal. (May 2007). "2,5-Disubstituted pyridines: the discovery of a novel series of 5-HT2A ligands". Bioorganic & Medicinal Chemistry Letters. 17 (9): 2643–2648. doi:10.1016/j.bmcl.2007.01.098. PMID17314044.
Nilsson T, Longmore J, Shaw D, Pantev E, Bard JA, Branchek T, etal. (May 1999). "Characterisation of 5-HT receptors in human coronary arteries by molecular and pharmacological techniques". European Journal of Pharmacology. 372 (1): 49–56. doi:10.1016/S0014-2999(99)00114-4. PMID10374714.
Nagatomo T, Rashid M, Abul Muntasir H, Komiyama T (October 2004). "Functions of 5-HT2A receptor and its antagonists in the cardiovascular system". Pharmacology & Therapeutics. 104 (1): 59–81. doi:10.1016/j.pharmthera.2004.08.005. PMID15500909.
Gardell LR, Vanover KE, Pounds L, Johnson RW, Barido R, Anderson GT, etal. (August 2007). "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. doi:10.1124/jpet.107.121715. PMID17519387. S2CID28861527.
Moya PR, Berg KA, Gutiérrez-Hernandez MA, Sáez-Briones P, Reyes-Parada M, Cassels BK, etal. (June 2007). "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. doi:10.1124/jpet.106.117507. PMID17337633. S2CID11651502.
Cussac D, Boutet-Robinet E, Ailhaud MC, Newman-Tancredi A, Martel JC, Danty N, etal. (October 2008). "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. doi:10.1016/j.ejphar.2008.07.040. PMID18703043.
Goldstein AT, Pukall C, Goldstein IL (2020). "Fibromyalgia and Female Sexual Pain Disorders". Female Sexual Pain Disorders: Evaluation and Management (2ed.). Wiley. ISBN978-1119482666.
Cao X, Wang Y, Shu D, Qu H, Luo C, Hu X (October 2020). "Food intake-related genes in chicken determined through combinatorial genome-wide association study and transcriptome analysis". Animal Genetics. 51 (5): 741–751. doi:10.1111/age.12980. PMID32720725. S2CID220839883.
Garza-Brenner E, Sifuentes-Rincón AM, Randel RD, Paredes-Sánchez FA, Parra-Bracamonte GM, Arellano Vera W, etal. (August 2017). "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. doi:10.1007/s13353-016-0383-0. PMID27987181. S2CID34463383.
Choi MJ, Lee HJ, Lee HJ, Ham BJ, Cha JH, Ryu SH, etal. (2004). "Association between major depressive disorder and the -1438A/G polymorphism of the serotonin 2A receptor gene". Neuropsychobiology. 49 (1): 38–41. doi:10.1159/000075337. PMID14730199. S2CID19528052.
Williams J, Spurlock G, McGuffin P, Mallet J, Nöthen MM, Gill M, etal. (May 1996). "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. doi:10.1016/s0140-6736(96)90939-3. PMID8622505. S2CID8510590.
Vaquero-Lorenzo C, Baca-Garcia E, Diaz-Hernandez M, Perez-Rodriguez MM, Fernandez-Navarro P, Giner L, etal. (July 2008). "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. doi:10.1002/ajmg.b.30642. PMID18163387. S2CID31504282.
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. doi:10.2174/092986707781368450. PMID17691947.
Ghasemi A, Seifi M, Baybordi F, Danaei N, Samadi Rad B (June 2018). "Association between serotonin 2A receptor genetic variations, stressful life events and suicide". Gene. 658: 191–197. doi:10.1016/j.gene.2018.03.023. PMID29526601. S2CID4854262.
Videtic A, Pungercic G, Pajnic IZ, Zupanc T, Balazic J, Tomori M, etal. (September 2006). "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. doi:10.1002/ajmg.b.30390. PMID16856120. S2CID9279191.
da Silva Junior FC, Araujo RM, Sarmento AS, de Carvalho MM, Fernandes HF, Yoshioka FK, etal. (December 2020). "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. doi:10.1016/j.genrep.2020.100889. S2CID224859807.
Lemaire C, Cantineau R, Guillaume M, Plenevaux A, Christiaens L (December 1991). "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. PMID1744713.
Rosier A, Dupont P, Peuskens J, Bormans G, Vandenberghe R, Maes M, etal. (November 1996). "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. doi:10.1016/S0925-4927(96)02806-5. PMID9027929. S2CID32317795.
Adams KH, Pinborg LH, Svarer C, Hasselbalch SG, Holm S, Haugbøl S, etal. (March 2004). "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. doi:10.1016/j.neuroimage.2003.10.046. PMID15006678. S2CID24403109.
