title: Effects of alinidine (ST 567) on baroreceptor-heart rate reflexes and its interactions with clonidine on the baroreflex and on the sympathetic terminals of the isolated atrium.
abstract: Alinidine (ST 567), an N-allyl derivative of clonidine, slowed the heart rate of conscious rabbits by 41 +/- 2.3 (S.E.D.) b/min and reduced mean arterial pressure (MAP) by 6.4 +/- 1.4 mmHg (P less than 0.001). The cardiac slowing was considered to be a direct effect in agreement with previous findings by others, since it was present in rabbits without functioning autonomic nerves, but the fall in blood pressure did not occur in these animals. Alinidine produced no significant changes in the reflex tachycardia response evoked by infusing nitroprusside, or in the pressure-related parameters of the MAP-heart period (HP) curve of the baroreceptor-heart rate reflex (i.e. HP range, gain, or median blood pressure BP50). Intravenous (i.v.) clonidine produced characteristic rises in baroreflex HP range and gain, which were due to vagal facilitation, and also produced falls in BP50 and resting MAP. I.v. alinidine suppressed the clonidine-induced vagal facilitation, but had no effect on the blood pressure changes. Intracisternal alinidine could be given in only relatively low dose, but reduced the clonidine-induced rise in vagal component of HP range. The main site of antagonism between i.v. alinidine and clonidine was probably in the CNS. We studied the nature of the antagonism at the sympathetic nerve terminal of the isolated left guinea pig atrium. Clonidine depressed the inotropic response to field stimulation of the sympathetic nerves and this was competitively antagonised by phentolamine greater than yohimbine greater than alinidine at potencies of about 1200:80:1. Alinidine was considered to be a weak but specific alpha 2-antagonist; it has no alpha 1-antagonist properties since it was without effect on the contractile response to noradrenaline of the guinea pig aorta. The alpha 2-antagonist property explains the suppression by alinidine of the clonidine-induced facilitation of the vagal component of the baroreceptor-heart rate reflex.
mesh_terms: D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006321:Heart / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009411:Nerve Endings / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects*; D011817:Rabbits; D012018:Reflex / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects*
chemical_list: D009599:Nitroprusside; C022192:alinidine; D007545:Isoproterenol; D003000:Clonidine