5-HT2A receptor antagonist

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>. 

In experimental studies, many clinically effective neuroleptics have been shown to act as 5-HT2A receptor antagonists. Studies on post-mortem brain from schizophrenic patients have shown that the decrease in the number of 5-HT2A receptors in the prefrontal cortex might be related to the disease process. It therefore seems unlikely that the antipsychotic activity of neuroleptics can be explained solely in terms of their action on 5-HT receptors. Furthermore, no correlation exists between the average therapeutic doses of a neuroleptic and its affinity for 5-HT receptors. It does seem possible, however, that several atypical neuroleptics such as amperozide, risperidone and possibly ritanserin do owe at least part of the pharmacological profile to their ability to inhibit 5-HT receptors. 

Risperidone has been developed as a combined D2/5-HT2A receptor antagonist. In addition, it has a high affinity for 5-HT1A and 5-HT7 receptors. Whether such an effect has any relevance to its beneficial effects on the negative symptoms of schizophrenia, and lack of extrapyramidal side effects at moderate therapeutic doses, is unknown. An important advantage of risperidone over clozapine lies in its lack of antagonism of muscarinic receptors. 

Marek, G. J., Martin-Ruiz, R., Abo, A. Artigas, F. (2005). The selective 5-HT2A receptor antagonist Ml00907 enhances antidepressant-like behavioral effects of the SSRI fluoxetine. Neuropsychopharmacology, 30, 2205-2215. 

Marek GJ, Aghajanian GK. 1994. Excitation of intemeurons in piriform cortex by 5-hydroxytryptamine Blockade by MDL 100,907, a highly selective 5-HT2A receptor antagonist. Eur J Pharmacol 259 137-141. 

Borowski, T., Krol, M., Broclawik, E., Baranowski, T, Strekowski, L. and Mokrosz, M.J. (2000) Application of similarity matrices and genetic neural networks in quantitative structure-activity relationships of 2- or 4-(4-methylpiperazino) pyrimidines 5-HT2A receptor antagonists./. Med. Chem., 43, 1901-1909. 

Nomura S, Shouza A, Omoto S, et al. 5-HT2A receptor antagonist increases circulating adiponectin in patients with type 2 diabetes. Blood Coagul Fibrinolysis 2005 16 423-428. 

Iloperidone is a novel antipsychotic drug which is a mixed dopamine D2/serotonin 5-HT2A receptor antagonist. In 2008, the US Food and Drug Administration required Vanda Pharmaceuticals, the manufacturers, to carry out a comparison of iloperidone with placebo and an active comparator such as olanzapine or risperidone [80 ]. It was finally approved in the USA in May 2009. 

Dual acting norepinephrine reuptake inhibitors and 5-HT2A receptor antagonists I Synthesis and activity of novel 3-(phenylsulfonyl)-1H-indoles... 

The second type of receptor used by JC virus is the serotonin receptor 5-HT2A, a G protein-coupled receptor with seven transmembrane domains. The involvement of this cell surface receptor in JV virus entry has been demonstrated by the inhibitory effect of 5-HT2A receptor antagonists and monoclonal antibodies directed against 5-HT2A receptors. Oligodendrocyte progenitor cells, which express this particular serotonin receptor, are susceptible to JC virus... 

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