5-HT2A receptor

Some neuroleptics, including clozapine, are potent 5-HT-receptor antagonists and the possible role of 5-HT in the action of neuroleptics and the development of schizophrenia has recently generated much interest (Busatto and Kerwin 1997). This has centred primarily on 5-HT2A receptors found in the limbic cortex, which are linked to neuronal excitation and believed to mediate the hallucinogenic effects of drugs such as lysergic acid diethylamide (LSD). 

Fibres from 5-HT neurons in the raphe nucleus innervate and yet, despite the observed 5-HT2A receptor link with neuronal excitation, appear to inhibit DA neurons in the SN (A9). Thus antagonism of 5-HT released onto them would increase their firing and so reduce the likelihood of EPSs, although how 5-HT2A antagonists can... 

Structurally quetiapine is related to clozapine and olanzapine. Quetiapine has high affinity for 5-HT2A receptors and lower... 

Arranz, M.)., Collier, D., Sodhi, M. et al. (1995). Association between clozapine response and allelic variation in 5-HT2A receptor gene. Lancet, 346,281-2. 

Arranz, M. J., Collier, D. A., Munro, J. etal. (1996). Analysis of a structural polymorphism in the 5-HT2A receptor and clinical response to clozapine. Neurosci. Lett. 217, 177-8. 

Arranz, M. J., Munro, J., Owen, M. J. et al. (1998). Evidence for association between polymorphisms in the promoter and coding regions of the 5-HT2A receptor gene and response to clozapine. Mol. Psychiatry, 3, 61-6. 

Erdmann, J., Shimron-Abarbanell, D., Rietschel, M. etal. (1996). Systematic screening for mutations in the human serotonin-2A (5-HT2a) receptor gene identification of two naturally occurring receptor variants and association analysis in schizophrenia. Hum. Genet., 97, 614-19. 

Malhotra, A., Goldman, D., Ozaki, N. etal (1996a). Lack of association between polymorphisms in the 5-HT2A receptor gene and the antipsychotic response to clozapine. Am. J. Psychiatry, 153, 1092. ... 

Nothen, M. M., Rietschel, M., Erdmann, J. etal. (1995). Genetic variation ofthe 5-HT2A receptor and response to clozapine. Lancet, 346, 908-9. 

Skrebuhhova, T., Allikmets, L. Matto, V. (1999). 5-HT2A receptors mediate the effects of antidepressants in the elevated plus-maze test but have a partial role in the forced swim test. Med. Sci. Res., 27, 277-80. 

Wang, Y. H., Shi, Z. Y., Zhao, G. Q. et al. (2006). Association between 5-HT2A receptor gene polymorphism and risperidone treatment response in the first episode (drug-naive) Chinese patients with schizophrenia. Chinese Journal of Nervous and Mental Diseases, 32(4), 294-9. 

Zhang, X. B., Sha, W. W., Zhang, Z. J. et al. (2005).T102C polymorphism in 5-HT2A receptor gene andtarditive dyskinesia in chronic schizophrenia. Chinese Mental Health Journal, 19(1), 8-10. 

Bortolozzi, A., Diaz-Mataix, L., Scorza, M. C., Celada, P. Artigas, F. (2005). The activation of 5-HT2a receptors in prefrontal cortex enhances dopaminergic activity. J. Neurochem. 95, 1597-607. 

Fay, R. Kubin, L. (2000). Pontomedullary distribution of 5-HT2A receptor-like protein in the rat. J. Comp. Neurol. 418, 323-45. 

Hamada, S., Senzaki, K., Hamaguchi-Hamada, K. et al. (1998). Localization of 5-HT2a receptor in rat cerebral cortex and olfactory system revealed by immuno-histochemistry using two antibodies raised in rabbit and chicken. Molec. Brain Res. 54, 199-211. 

Lopez-Gimenez, J. F., Vilaro, M. T., Palacios, J. M. Mengod, G. (2001). Mapping of 5-HT2a receptors and their mRNA in monkey brain [3H]MDL100,907 autoradiography and in situ hybridization studies. J. Comp. Neurol. 429, 571-89. 

Bull, E.J., Hutson, P.H., and Fone, K.C., Decreased social behaviour following 3,4-methylene-dioxymethamphetamine (MDMA) is accompanied by changes in 5-HT2A receptor responsivity, Neuropharmacology 46(2), 202-210, 2004. 

Table 11.4 shows that clozapine has approximately 10 times higher affinity for the D4 and 5-HT2A-receptors than the D2-receptor and shows a greater occupancy of the 5-HT2 than the D2-like receptors. The other atypical neuroleptic risperidone has a similar affinity for the two D2-like receptors but an affinity for the 5-HT2a-receptor that is just over 3 times lower than for the D2-receptor. Receptor occupancy in vivo shows a similar profile to clozapine. In contrast, haloperidol s affinity for the D4-receptor is just under 3 times lower and over 100 times lower for the 5-HT2a-receptor, with no binding to the latter in vivo. The fractional occupancy of striatal... 

DV-7028 (3- 2-[4-(4-fluorobenzoyl)piperidin-Tyl]ethyl -6,7,8,9-tetrahydro-27/-pyrido[l,2- ][l,3,5]triazine-2,4(3//)-dione maleate, 150 (Figure 4) a 5-HT2A-receptor antagonist, exhibited cardiovascular effects in a rat model C1998MI266, 1996MI325, 1998MI259>. 

Masellis M, Paterson AD, Badri F, Lieberman JA, Meltzer HY, Cavazzoni P et al. Genetic variation of 5-HT2A receptor and response to clozapine [letter comment]. Lancet 1995 346(8982) 1108. 

---