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-HT1A 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 flesinoxan or 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-HT1A antagonists methiothepin, buspirone, spiroxatrine and 8-MeO-C1EPAT (8-methoxy-2-(N-2-cholroethyl-N-n-propylamino)tetralin). 8-MeO-C1EPAT appeared to be the most suitable antagonist in this model. The 5-HT1C, 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-HT1A receptors in the cardiovascular effects of flesinoxan and 8-OH-DPAT.
Dreteler
G H
GH
Department of Pharmacology, Duphar B.V., Weesp, The Netherlands.
Wouters
W
W
Saxena
P R
PR
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000758:Anesthesia; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003655:Decerebrate State; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D017294:Ondansetron; D010879:Piperazines / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects; D016713:Ritanserin; D012702:Serotonin Antagonists / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D000959:Antihypertensive Agents; D007093:Imidazoles; D009281:Naphthalenes; D010879:Piperazines; D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D016713:Ritanserin; C056895:flesinoxan; D017294:Ondansetron; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D001285:Atropine