A comparative study of the effects of some 5-HT(1A) receptor agonists on the blood pressure of pithed rats

The intention of this study was to supply additional information about direct effects of the 5-HT(1A) receptor agonist indorenate on the arterial blood pressure. The effects of indorenate were compared with those of buspirone and ipsapirone (all selective 5-HT(1A) agonists) on the blood pressure of pithed rats. These compounds increased the blood pressure in a dose-dependent fashion. The effects of either ipsapirone or buspirone were clearly inhibited with 100 μg/kg of prazosin (selective α₁-adrenoceptor antagonist), whereas 1 mg/kg of this blocker elicited only a mild inhibition of the presser effect of indorenate. Pindolol (100 μg/kg; a β-adrenoceptor and 5-HT(1A), receptor blocker) was unable to modify the effects of all the 5-HT(1A) agonists tested. In addition, the 5-HT₂ receptor and weak α₁-adrenoceptor blocker ketanserin (10 - 100 μg/kg)antagonized the presser effect of indorenate.Nevertheless, only a mild inhibition was observed in the case of both ipsapirone and buspirone. On the other hand, the latter drugs diminished the blood pressure of pithed rats intravenously infused with norepinephrine, but indorenate was inactive. However, in rats infused with quipazine, all the 5- HT(1A) agonists failed to reduce blood pressure. These results indicate that buspirone and ipsapirone behaved as partial α₁-adrenoceptor agonists. Furthermore, the results show that indorenate- elicited presser effects are probably due to stimulation of 5-HT₂ receptors. Thus, unlike ipsapirone and buspirone, indorenate did not show conclusively activity related with α₁-adrenoceptors.