Peripheral Vascular Effects of a New Dopamine Analog: 5–6-Dihydroxy-2-methylaminotetralin (M-8)

SUMMARYIt has been reported that the cyclic dopamine analog 5,6-dihydroxy-2-methylaminotetralin (M-8) is an adrenergic agonist in the dog. In this study, the effects of M-8 on hindlimb vascular responses were determined in the dog. In group I (n = 10), hindlimb vascular responses to ipsilateral femoral artery injections of M-8 before and after adrenergic blockade were determined. Mean femoral artery and peripheral venous pressures and heart rate responses to intra-arterial injections of M-8 were recorded. Mean femoral artery flows were measured by an electromagnetic flowmeter. Low doses of M-8 (0.0001–0.1 μg/kg) elicited transient dilatory responses, while higher doses (1–10 μg/kg) produced a biphasic response consisting of a dilation followed by constriction. The dilatory responses were attenuated following pre-treatment with propranolol and were augmented by pretreatment with phenoxybenzamine. The constrictor responses were attenuated by pretreatment with phenoxybenzamine and augmented by pretreatment with propranolol. These responses were not reflex-mediated, since the hemodynamic parameters in the contralateral limb were not altered during the depressor or pressor phases. In group II (n = 5), the effects of intra-arterially infused M-8 (0.01 μg/kg/min) on plethysmographically determined hindlimb venous capacitance were determined. Intra-arterial infusion increased venous capacitance through β-adrenergic mechanisms without altering mean arterial pressure and heart rate or contralateral limb mean femoral artery flows. M-8 is a potent peripherally acting adrenergic agent.