Premium
Investigation of the negative chronotropic action of SK&F 86466 in the pithed normotensive rat
Author(s) -
Jim Kam F.,
Macia Richard A.,
Matthews William D.
Publication year - 1986
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430090305
Subject(s) - hexamethonium , chronotropic , medicine , atropine , bradycardia , endocrinology , propranolol , reserpine , vagotomy , chemistry , phenylephrine , reflex bradycardia , heart rate , blood pressure
SK&F 86466, 6‐chloro‐3‐methyl‐2,3,4,5‐tetrahydro‐1‐H‐3‐benzazepine, is a potent and selective antagonist of the α 2 ‐adrenoceptor in vitro. This compound produced a small pressor response accompanied by a marked bradycardia when administered i.v. to the pithed normotensive rat. The pressor response was not affected by reserpine treatment, pretreatment with α‐ or β‐adrenoceptor antagonists, atropine, or hexamethonium. The bradycardia was markedly reduced by bilateral vagotomy and pretreatment with atropine and attenuated by hexamethonium. The negative chronotropic action of SK&F 86466 was abolished by a combination of vagotomy and atropine. Mediation of the bradycardia by a baroreceptor reflex was ruled out by the observations that a lack of change in heart rate was associated with the vasopressor response to phenylephrine in the pithed rat pretreated with propranolol. It is concluded that the negative chronotropic action of SK&F 86466 in the pithed rat is mediated indirectly by activation of the cholinergic innervation of the heart.