Peripheral vascular effects of a new dopamine analog: 5-6-dihydroxy-2-methylaminotetralin (M-8)

It has been reported that the cyclic dopamine analog 5,6-dihydroxy-2-methylaminotetralin (M-8) in an adrenergic agonist in the dog. In this study, the effects of M-8 on hindlimb vascular responses was 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 (0.0001-01 micrograms/kg) elicited transient dilatory responses, while higher doses (1-10 micrograms/kg) produced a biphasic response consisting of a dilation followed by constriction. The dilatory responses were attenuated following pretreatment with propranolol and were augmented by pretreatment with phenoxybenzamine. The constrictor responses were attenuated by pretreatment with phenoxybenzamine. The constrictor responses were attenuated by pretreatment with pehnoxybenzamine 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 micrograms/kg/min) on plethysmographically determined hindlimb venous capacitance were determined. Intra-arterial infusion increased venous capacitance through beta-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.