Abstract
1. 1. HT-90B ((−)-N-[2-(8-methyl-1,4-benzodioxane-2-ylmethyl)amino]ethyl]tricyclo[3,3,1,1(3,7)] decane-1-carboxamide) had high affinities for the 5-HT 1A (Ki =0.18 nM) and 5-HT 2 (Ki = 9.2 nM) receptors. 2. 2. HT-90B inhibited forskolin activated adenylate cyclase in rat hippocampal membranes as a 5-HT 1A full agonist (IC 50 = 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-HT 1A agonist. 3. 3. In the serotonin syndrome test, HT-90B behaved as a weak partial 5-HT 1A agonist in reserpinized rats. 4. 4. 5-HT 2 receptor-mediated potentiation of rabbit platelet aggregation by serotonin (5-HT) was reduced by HT-90B (IC 50 = 1.73 μM). 5. 5. Head twitch response induced by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DO1), a 5-HT 2 agonist, was inhibited by HT-90B in mice. 6. 6. It is concluded that HT-90B has potent 5-HT 1A receptor agonist as well as 5-HT 2 receptor antagonist properties in vitro and in vivo.
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