CENTRAL AND PERIPHERAL ALPHA-ADRENOCEPTOR ACTIONS OF AMITRAZ IN THE DOG

The aim of this study was to determine the contribution of α2‐and α1 adrenoceptor agonist activity of the formamidine, amitraz, on peripheral circulation in the dog. Intra‐arterial injections of amitraz (0.25‐5.0 μg/kg) produced a dose‐dependent increase in perfusion pressure in the autoperfused hind limbs of methoxyflurane‐anaesthetized dogs. A constant blood flow to the hind limbs was maintained using a peristaltic pump. Intravenous phentolamine (0.5 mg/kg), prazosin (35 μg/kg) and yohimbine (10 μg/kg) in separate experiments antagonized the vasoconstrictor actions of amitraz and produced a parallel shift to the right of the amitraz dose‐response curve. Cumulative doses of amitraz (0.5‐15 μg/kg) given by intracisterna magna (i.c.m.) injections reduced mean arterial pressure and heart rate in a dose‐dependent manner. Similar responses were produced by intravenous amitraz but at much higher doses. In separate experiments amitraz‐induced hypotension (doses up to 25 μg/kg i.c.m.) was prevented by pre‐treatment with yohimbine (30 μg/kg i.c.m.) but not prazosin (20 μg/kg i.c.m.). Both antagonists partially inhibited the bradycardia produced by amitraz. It is concluded that amitraz stimulates α1‐and α2‐adrenoceptors to produce vascular constriction. The central hypotensive action of amitraz appears to be mediated by α2‐adrenoceptors; however, both receptor subtypes appear to be stimulated to produce bradycardia. Copyright © 1990, Wiley Blackwell. All rights reserved