Effects of tertatolol, a β-adrenoceptor antagonist with agonist affinity at 5-HT 1A receptors, in an animal model of migraine: comparison with propranolol and pindolol

Abstract

Constriction of carotid arteriovenous anastomoses is a common property of several antimigraine drugs. The present study concerns the effects of tertatolol (0.1, 0.3, 1 and 3 mg/kg i.v.), a novel β-adrenoceptor antagonist with an agonist action on 5-HT 1A receptors, on systemic haemodynamics and carotid blood flow distribution in the anaesthetized pig. Two other β-adrenoceptor antagonists, one (propranolol) with and one (pindolol) without antimigraine actions, were compared (doses: 0.03, 0.1, 0.3 and 1 mg/kg i.v.) with tertatolol in this animal experimental model of migraine. While the β-adrenoceptor antagonist with partial agonist action, pindolol, increased heart rate and cardiac output, propranolol and tertatolol decreased these variables moderately. Mean arterial blood pressure also decreased with the two highest doses of propranolol and with the highest dose of tertatolol. The calculated total peripheral conductance decreased with the first three doses of tertatolol. Carotid haemodynamic variables were not affected by pindolol, except for some increase in the nutrient fraction after the highest dose. Propranolol and especially tertatolol decreased both total carotid blood flow and arteriovenous anastomotic blood flow without affecting the nutrient fraction. In the case of tertatolol, blood flow decreases were accompanied by similar decreases in vascular conductance, indicating active arteriovenous anastomotic constriction. It is therefore suggested that tertatolol may prove effective in the treatment of migraine.