title: Pharmacological profile of (-)HT-90B, a novel 5-HT1A receptor agonist/5-HT2 receptor antagonist.
abstract: 1. HT-90B ((-)-N-([2-(8-methyl-l, 4-benzodioxane-2-ylmethyl)amino]ethyl) tricyclo[3,3,1,1(3.7)] decane-1-carboxamide) had high affinities for the 5-HT1A (Ki = 0.18 nM) and 5-HT2 (Ki = 9.2 nM) receptors. 2. HT-90B inhibited forskolin activated adenylate cyclase in rat hippocampal membranes as a 5-HT1A full agonist (IC50 = 2 nM), and the potency of the drug was higher than that of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a standard 5-HT1A agonist. 3. In the serotonin syndrome test, HT-90B behaved as a weak partial 5-HT1A agonist in reserpinized rats. 4. 5-HT2 receptor-mediated potentiation of rabbit platelet aggregation by serotonin (5-HT) was reduced by HT-90B (IC50 = 1.73 microM). 5. Head twitch response induced by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT2 agonist, was inhibited by HT-90B in mice. 6. It is concluded that HT-90B has potent 5-HT1A receptor agonist as well as 5-HT2 receptor antagonist properties in vitro and in vivo.
authors.affiliation: Fuji Gotemba Research Labs., Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Uchida
authors.forename: K
authors.initials: K
authors.lastname: Inagawa
authors.forename: C
authors.initials: C
authors.lastname: Tameda
authors.forename: T
authors.initials: T
authors.lastname: Miyauchi
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D002065:Buspirone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: C098902:HT 90B; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000218:Adamantane; D002065:Buspirone