The Hypotensive Effect of BMY 7378 Is Antagonized by a Silent 5-HT 1A Receptor Antagonist : Comparison With 8-Hydroxy-dipropylamino Tetralin

Abstract

Background Stimulation of central 5-HT 1A receptors produces bradycardia and diminishes blood pressure in conscious or anesthetized rats. Our objective was to investigate the effects on blood pressure and heart rate of the partial 5-HT 1A receptor agonist and selective α 1D-adrenoceptor antagonist BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-8-azaspiro [4.5] decane-7,9 dione hydrochloride) compared to the full 5-HT 1A receptor agonist 8-OH-DPAT (8-hydroxy-dipropylamino tetralin) in adult anesthetized rats. 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 presence of WAY 100635. Blood pressure and heart rate were continuously recorded. Results BMY 7378 induced a decrease in blood pressure with no apparent change 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-HT 1A receptor antagonist WAY 100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride). However, a remnant yet significant hypotensive effect was not blocked by the antagonist. In contrast, 8-OH-DPAT actions were completely blocked by WAY 100635. Conclusions Data suggest that BMY 7378 cardiovascular effects are related to activation, as a full agonist, of central 5-HT 1A receptors in adult rats; however, participation of other systems such as vascular α 1-adrenoceptors in cardiovascular function is suggested.