Comparison of the cardiovascular effects of the 5-HT1A receptor agonist flesinoxan with that of 8-OH-DPAT in the rat

The cardiovascular response to flesinoxan and 8-OH-DPAT (8-hydroxy-2-(di-N-propylamino)tetralin), 5-HT_1A receptor agonists, has been investigated in anaesthetized Wistar rats and spontaneously hypertensive rats (SHR) and in conscious SHR. Flesinoxan and 8-OH-DPAT potently lowered blood pressure and heart rate in these models. In conscious SHR, atropine reversed the bradycardia induced by flesinoxan partially and that induced by 8-OH-DPAT completely. In pithed rats with vasopressin-raised blood pressure, neither flesinoxan nor 8-OH-DPAT lowered blood pressure or heart rate. Intracisternal administration of either flesinoxanor 8-OH-DPAT was less efficacious than intravenous administration. The cardiovascular responses to flesinoxan and 8-OH-DPAT in the anaesthetized Wistar were inhibited by the putative 5-HT_1A antagonists methiothepin, buspirone, spiroxatrine and 8-MeO-C1EPAT (8-methoxy-2-(N-2-chloroethyl-N-n-propylamino)tetralin). 8-MeO-C1EPAT appeared to be the most suitable antagonist in this model. The 5-HT_1C, 5-HT₂ antagonist ritanserin or the 5-HT₃ antagonist GR 38032F had no effect on the responses to flesinoxan or 8-OH-DPAT. In conscious SHR however, 8-MeO-C1EPAT did not antagonize these cardiovascular responses. This study confirms the involvement of central 5-HT_1A receptors in the cardiovascular effects of flesinoxan and 8-OH-DPAT.