The hypotensive effect of BMY 7378 is antagonized by a silent 5-HT1A receptor antagonist: Comparison with 8-hydroxy-dipropylamino tetralin

Background. Stimulation of central 5-HT1A receptors produces bradycardia an d diminishes blood pressure in conscious or anesthetized rats. Our objectiv e was to investigate the effects on blood pressure and heart rate of the pa rtial 5-HT1A receptor agonist and selective alpha (1D)-adrenoceptor antagon ist BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-8-azaspiro [4 .5] decane-7,9 dione hydrochloride) compared to the full 5-HT1A receptor ag onist 8-OH-DPAT (8-hydroxy-dipropylamino tetralin) in adult anesthetized ra ts. Methods. Male Wistar rats of 6 months of age were exposed intravenously (i. v.) to increasing doses of BMY 7378 or 8-OH-DPAT in the absence and presenc e of WAY 100635. Blood pressure and heart rate were continuously recorded. Results. BMY 7378 induced a decrease in blood pressure with no apparent cha nge in heart rate compared to basal values, while 8-OH-DPAT decreased both hemodynamic parameters. BMY 7378 hypotensive effect was antagonized by the selective, silent 5-HT1A receptor antagonist WAY 100635 (N-[2-[4-(2-methoxy phenyl)-1-piperazinyl] ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihyd rochloride). However, a remnant yet significant hypotensive effect was not blocked by the antagonist. In contrast, 8-OH-DPAT actions were completely b locked by WAY 100635. Conclusions. Data suggest that BMY 7378 cardiovascular effects are related to activation, as a full agonist, of central 5-HT1A receptors in adult rats ; however, participation of other systems such as vascular alpha (1)-adreno ceptors in cardiovascular function is suggested. (C) 2001 IMSS. Published b y Elsevier Science Inc.