Flesinoxan lowers blood pressure and heart rate in cats via 5-HT1A receptors.
Flesinoxan, a new phenylpiperazine derivative has been shown to lower blood pressure in different species after both oral and i.v. administration. The present study shows that the hypotensive potency of flesinoxan in anaesthetised cats increased 35 times after administration via the vertebral arteries compared to i.v. administration. These results, which were confirmed by intracisternal administration, point strongly to a central site of action. Haemodynamic studies indicated that the blood pressure reduction in anaesthetised cats was mainly due to a reduction in the total peripheral resistance and only to some extent to a reduced cardiac output. Flesinoxan seems not to affect sympathetic function by a peripheral mechanism. Its cardiovascular profile can be explained by a centrally mediated reduction of sympathetic tone and increase in vagal tone. Receptor binding studies indicated that flesinoxan is a very potent and selective 5-HT1A ligand. The decreases in blood pressure and heart rate induced by centrally administered flesinoxan and 8-OH-DPAT, could be antagonized effectively by the putative 5-HT1A antagonist pindolol. This suggests a relationship between blood pressure reduction and central 5-HT1A receptors.
Wouters
W
W
Department of Pharmacology, Duphar B.V., Weesp, The Netherlands.
Tulp
M T
MT
Bevan
P
P
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002415:Cats; D002946:Cisterna Magna; D005260:Female; D005725:Ganglia, Autonomic / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D007269:Injections, Intra-Arterial; D008297:Male; D009541:Nictitating Membrane / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects; D014711:Vertebral Artery
D000959:Antihypertensive Agents; D010879:Piperazines; D011985:Receptors, Serotonin; D010656:Phenylephrine; C056895:flesinoxan