Studies on the hypotensive action of alpha-methyldopamine

1. Intraventricular alpha-methyldopamine (50-200 mug) produced a dose-related fall in blood pressure in conscious spontaneously hypertensive rats. Pretreatment with intraventricular 6-hydroxydopamine prevented this hypotensive effect of alpha-methyldopamine. 2. The hypotensive effect of alpha-methyldopamine was prevented by intraventricular injection of phentolamine or desmethylimipramine, but not by intraperitoneal injection of haloperidol. 3. Pretreatment with U-14,624, a selective central dopamine-beta-hydroxylase inhibitor, prevented the hypotensive effect of alpha-methyldopamine. 4. Alpha-methyldopamine was considerably less potent than noradrenaline as a pressor agent in the pithed rat, but noradrenaline and alpha-methylnoradrenaline were found to be equipotent. 5. Alpha-methyldopamine (1-5 mg i.c.v.) reduced pressor responses elicited by electrical stimulation of the midbrain reticular formation in cats anaesthetized with chloralose. 6. It is concluded that the hypotensive action of alpha-methyldopamine in conscious animals involves intact central alpha-adrenergic neurones and a central adrenergic uptake mechanism for the formation of alpha-methylnoradrenaline.