Preclinical pharmacology of B-20991, a 5-HT1A receptor agonist with anxiolytic activity

The purpose of this study was to characterize the pharmacological effects of 2-[[4-(o-methoxyphenyl)piperazin-1-yl]methyl]-1.3-dioxoperhydroimidazo[ 1,5-a]pyridine (B-20991) by using several biochemical and behavioral assays. Results of binding studies showed that B-20991 binds with high affinity to the 5-HT1A receptor (K-1 = 31.7 +/- 1.7 nM), moderate affinity to 5-HT3 receptor (K-1 = 269.4 +/- 23.2 nM) and low affinity (K-1 > 1000) to 5-HT2A receptor, dopamine D-2 receptor. benzodiazepine receptors and alpha(1)-adrenoceptor. The administration of B-20991 produced a dose and time related decrease in mouse rectal temperature, increased both lower lip retraction and fiat body posture behavioral scores in rat. decreased 5-hydroxytryptamine (5-HT. serotonin) neuronal activity in mouse hypothalamus, and did not alter dopamine neuronal activity not locomotor activity. The anxiolytic activity of B-20991 was assessed by using both the social interaction and light/dark box teats. The results of these tests indicated that B-20991 caused a dose-related increase in the social interaction and light/dark box behavioral scores. Taken together these results suggest that B-20991 is a 5-HT1A receptor agonist that exhibits anxiolytic activity. (C) 1998 Elsevier Science B.V.