5-HT2 receptor

DOI (294) and a-methyl-5-HT (295) are selective 5-HT2 receptor agonists. Ketansetin (296) and ritansetin (297) are potent and selective 5-HT2 antagonists. SB 200646 (298) is an antagonist which has greater selectivity toward 5-HT2g and receptors compared to the 5-HT2 subtype. 

Modulation of second-messenger pathways is also an attractive target upon which to base novel antidepressants. Rolipram [61413-54-5] an antidepressant in the preregistration phase, enhances the effects of noradrenaline though selective inhibition of central phosphodiesterase, an enzyme which degrades cycHc adenosiae monophosphate (cAMP). Modulation of the phosphatidyl iaositol second-messenger system coupled to, for example, 5-HT,, 5-HT,3, or 5-HT2( receptors might also lead to novel antidepressants, as well as to alternatives to lithium for treatment of mania. Novel compounds such as inhibitors of A-adenosyl-methionine or central catechol-0-methyltransferase also warrant attention. 

Correlation between clinical effectiveness and receptor affinities, however, can be seen with other receptors in addition to the dopamine D2 receptor. These include other dopaminergic receptors, as well as noradrenergic and serotonergic receptors. For example, most antipsychotics also have high affinity for a -adrenoceptors and 5-HT2 receptors (225). Some antipsychotics have been shown to be selective for the adrenoceptor versus the a -adrenoceptor, for example, spiperone [749-02-0] (226) and risperidone (61) (221]... 

Receptor binding studies have shown that H-LSD labels 5-HT2 receptors in neuronal tissue (Peroutka 1987). LSD has also been shown to bind with high affinity to a subtype of the 5-HTj receptor (5-HTjq), a site that also displays a high affinity for 5-HT (Glennon et al. 1986 Peroutka 1987). 

Of course, cholinergic neurons are not the only ones with axon terminals in the cortex and if their degeneration does originate in the cortex then other afferants and their neurons could also be affected. This contention is supported by reported reductions in the number of NA neurons in the locus coeruleus, and 5-HT neurons in dorsal raphe but these are less marked (approximately 50%) than the loss of cholinergic neurons. Accompanying reductions in cortical NA and 5-HT are also seen but are again lower than those for ChAT but 5-HT2 receptors are reduced (43%). 

Done, CJ and Sharp, T (1994) Biochemical evidence for the regulation of central noradrenergic activity by 5-HTia and 5-HT2 receptors Microdialysis studies in the awake and anaesthetised rat. Neuropharmacology 33 411-421. 

Mokrosz JL et al. (1995) Structure-activity relationship studies of CNS agents, XIX Quantitative analysis of the alkyl chain effects on the 5-HTlA and 5-HT2 receptor affinities of 4-alkyl-1-arylpiperazines and their analogs. Arch Pharm (Weinheim) 328(2) 143-148... 

QUESTION Would you expect the direct effects of MDMA on the 5-HT2 receptor to have any significance in the presence of this massive 5-HT release that it is causing ... 

Lyon, R.A. Davis, K.A. and Titeler, M. H-DOB (4-bromo-2,5-emethoxy-phenylisopropylamine) labels a guanine nucleotide-sensitive state of cortical 5-HT2 receptors. J Pharmacol Exp Ther 31 194-199, 1987. 

Titeler. M. Lyon, R.A. and Gleimon, R.A. Radioligand binding evidence implicates the brain 5-HT2 receptor as a site of action for LSD and phenylisopropyl amine hallucinogens. Psychopharmacol 94 213-216,... 

Blue, M.E. Yagaloff, K.A. Mamounas, L.A. Hartig, P.R. and Molliver, M.E. Correspondence of 5-HT2 receptor distribution with serotonin innervation in rat cerebral cortex. Abstr Soc Neurosci 12 145, 1986. 

ME. Correspondence between 5-HT2 receptors and serotonergic axons in rat neocortex. Brain Res 453 315-328, 1988b. 

Nimgaonkar, V. L., Zhang, X. R., Brar, J. S. et al. (1996). 5-HT2 receptor gene locus association with schizophrenia or treatment response not detected. Psychiatr. Genet., 6, 23-7. 

Drugs that target other sites of platelet action include thromboxane synthetase inhibitors, serotonin or 5-hydroxytryptamine (5-HT2) receptor blockers, and thromboxane A2 receptor blockers, in addition to cyclooxygenase inhibitors and prostaglandin analogues. 

Jiirgensen S, Dalbo S, Angers P, Santos AR, Ribeiro-do-Valle RM. Involvement of 5-HT2 receptors in the antinociceptive effect of Uncaria tomentosa. Pharmacol Biochem Behav 2005 81 466-477. 

Olijslagers J., Werkman T., McReary A. et al. (2004). 5-HT2 receptors differentially modulate dopamine-mediated auto-inhibition in A9 and A10 midbrain areas of the rat. Neuropharmacology 46, 504 10. 

More recently, the action of subtype-selective 5-HT2 receptor antagonists on sleep variables was assessed in the rat. Systemic administration of the 5-HT2a... 

Amici, R., Sanford, L. D., Kearney, K. et al. (2004). A serotonergic (5-HT2) receptor mechanism in the laterodorsal tegmental nucleus participates in regulating the pattern of rapid-eye-movement sleep occurrence in the rat. Brain Res. 996, 9-18. 

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