Serotonin-receptor subtypes

Buspirone, ipsaperone, sumatriptan, and cisapride are agonists whereas methysergide, risperidone, ketanserin, and ondansetron are antagonists at serotonin receptors. 

Sertaconazole nitrate is an antifnngal agent, which alters permeability of fnngal cell membrane, leading to cell death. It is indicated in the topical treatment of interdigital tinea pedis cansed by Trichophyton rubrum, Trichophyton men-tagrophytes, and Epidermophyton floccosum in immnno-competent patients. 

Tioconazole (Vagistat 1, others) is an imidazole that is marketed for treatment of Candida vnlvovaginitis. A single 4.6-g dose of ointment (300 mg) is given at bedtime. 

Oxiconazole, Sulconazole, and Sertaconazole are imidazole derivatives used for the topical treatment of infections cansed by the common pathogenic dermatophytes. Oxiconazole nitrate (Oxistat) is available as a cream and 

Sevelamer hydrochloride is a phosphate binder, which decreases intestinal phosphate absorption by binding to phosphate in the GI tract. It is indicated in the reduction of serum phosphorus in patients with chronic kidney disease who are on hemodialysis. 

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Future Outlook for Antidepressants. Third-generation antidepressants are expected to combine superior efficacy and improved safety, but are unlikely to reduce the onset of therapeutic action in depressed patients (179). Many dmgs in clinical development as antidepressive agents focus on estabhshed properties such as inhibition of serotonin, dopamine, and/or noradrenaline reuptake, agonistic or antagonistic action at various serotonin receptor subtypes, presynaptic tt2-adrenoceptor antagonism, or specific monoamine—oxidase type A inhibition. Examples include buspirone (3) (only... 

A therapeutic alternative for treatment of anxiety and depression is the use of 5-HT1A agonists. Azapirones comprise the major class of 5-HT1A agonists of which buspirone (Buspar [4]) is the only FDA-approved 5-HT1A selective agonist (relative to the other 13 serotonin receptor subtypes) for anxiety currently on the US market (Scheme 19.1). Buspirone has shown efficacy in randomized controlled trials of GAD for which it was approved [5-7]. Unlike benzodiazepines, buspirone is not addictive... 

Kiefei JM, Cooper ML, Bodnar RJ. (1992b). Serotonin receptor subtype antagonists in the mediai ventrai meduiia inhibit mesencephaiic opiate anaigesia. Brain Res. 597 331-38. 

Dennis J. McKenna and Stephen J. Peroutka. "Serotonin neuro-toxins Focus on MDMA (3,4-methylenedioxymethampheta-mine, Ecstasy )." In Serotonin Receptor Subtypes Basic and Clinical Aspects, edited by S. J. Peroutka, pp. 127 8. New York Alan R. Liss Publishers, 1990. 

Fig. 9.8 Examples of rule-of-three compliant molecules that have biological activity better than 10 nM. Under each molecule, the following information is included molecule name, MW, ClogP, the biological activity type, value and target. Target names are as follows D3 and D4 - dopaminergic receptor types 2 and 3 AChE and BChE - acetyl- and butyryl-choline esterases PRa and PRb - progesterone receptor types A and B H] and H3, histamine receptor types 1 and 3 5-HT2a, 5-HT2b, 5-HT2c, 5-HT3, 5-HT4 - serotonin receptor subtypes 2A, 2B, 2C, and types 3 and 4 DAT, NET, 5-HTT - dopamine, norepinephrine and serotonin transporter proteins /X], /x.2, S, ki, ks - opioid receptor types mu-1, mu-2, delta, kappa-1 and kappa-3 5a-Rl and 5o -R2 - 5-alpha-reductase isozymes 1 and 2 Flt-1-fms-like tyrosine kinase receptor.

Table 6.2. Serotonin receptor subtypes and disease states...

Physiological or pathological condition Serotonin receptor subtype implicated... 

Koella has reviewed the evidence implicating the involvement of serotonin in the sleep-wake cycle but the involvement of specific serotonin receptor subtypes in sleep mechanisms is unclear. Experimental evidence suggests that 5-HTia agonists delay the onset of REM sleep while 5-HT2 antagonists suppress REM and have variable effects on non-REM sleep. 

To date, at least four major subtypes of serotonin receptor have been described in detail and a major advance has been made with the isolation of genomic clones for these receptor subtypes. We now await the further development of selective ligands for all the serotonin receptor subtypes which may ultimately lead to a better understanding of the functional significance and clinical relevance of serotonin receptors in health and disease. Hopefully such a development will also result in the availability of more effective drugs to treat neurological and psychiatric diseases. 

Pharmacology Naratriptan, rizatriptan, sumatriptan, frovatriptan, almotriptan, eletriptan, and zolmitriptan are selective agonists for a vascular 5-hydroxytryptamine-i(serotonin) receptor subtype. Use of 5-HT- agonists results in... 

Researchers are currently attempting to develop new potential anxiolytic drugs by targeting various serotonin receptors selectively. Among 18 or more identified serotonin receptors subtypes, it seems that S-HTj, ... 

A decline in trophic factors may contribute to aging, and a reduced level of hippocampal 5-HT, receptors in Alzheimer s disease would lead to decreased release of S-100 and increased levels of S-100 within cells (Griffin et al. 1989). The relevance of such changes to neuronal cell loss in the hippocampus and cortex remains to be established. The possibility that other serotonin receptor subtypes may also regulate the release of trophic factors remains to be determined (Whitaker-Azmitia and Azmitia 1991], as does the search for other neuronal growth factors (Zhou and Azmitia 1991]. However, such factors and the involvement of serotonin in their release may subsequently be shown to afford a site of drug action to attenuate cell decline and cognitive impairment. 

Kunovac JL, Stahl SM Biochemical pharmacology of serotonin receptor subtypes hypothesis for clinical applications of selective serotonin ligands. International Review of Psychiatry 7 55-67, 1995... 

Murphy DL Neuropsychiatric disorders and the multiple human brain serotonin receptor subtypes and subsystems. Neuropsychopharmacology 3 457, 1990 Murphy DL, Beigel A, Weingartner H, et al The quantification of manic behavior, in Psychological Measurements in Psychopharmacology. Edited by Pichot P. Basel, Switzerland, Karger, 1974a, pp 203-220... 

S. J. Peroutka (1995). Serotonin receptor subtypes Their evolution and clinical significance. CNS Drugs 4 19. 

P. R. Saxena (1995). Serotonin receptors subtypes, functional responses and therapeutic relevance. Pharmacol. Ther. 66 339. 

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