Are drugs that act both on serotonin receptors and alpha 1-adrenoceptors more potent hypotensive agents than those that act only on alpha 1-adrenoceptors?
Simultaneous recordings of cardiac, splanchnic, and renal nerve activity, blood pressure, heart rate, and femoral arterial conductance were made in anaesthetised paralysed cats. Cumulative dose-response curves were constructed for either cinanserin or 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in animals that had received a maximal hypotensive dose of prazosin that had, in addition to decreasing blood pressure, decreased heart rate and background activity in all three nerves. Cinanserin failed to further affect these parameters. However, 8-OH-DPAT caused further falls in blood pressure and heart rate and virtually abolished the remaining activity in all nerves. Part of the extra decrease in heart rate was shown to be due to an increase in vagal tone. It was concluded that if a drug has both an agonist action at the putative 5-HT1A receptors and an antagonist action at alpha 1-adrenoceptors, it is a more potent hypotensive agent than if it only blocks alpha 1-adrenoceptors. These observations do not support a role for 5-HT2 receptors in the maintenance of blood pressure.
Ramage
A G
AG
Academic Department of Pharmacology, Royal Free Hospital School of Medicine, Hampstead, London, U.K.
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002415:Cats; D002928:Cinanserin / Q000494:pharmacology; D004873:Ergolines / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D016713:Ritanserin; D012702:Serotonin Antagonists / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D004873:Ergolines; D010880:Piperidines; D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D016713:Ritanserin; D008711:Metergoline; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; D002928:Cinanserin; C032663:LY 53857; D011224:Prazosin