Differential competition by L-alpha-methyldopa metabolites for adrenergic receptors in rat forebrain.
The capacity of a series of intraneuronal metabolites of L-alpha-methyldopa to compete for alpha-1 ([3H]prazosin, alpha-2([3H]clonidine and beta ([3H]dihydroalprenolol) receptor binding in rat forebrain was studied. Each metabolite studied had a unique order of activity at each receptor. These data show that (-)-erythro-alpha-methylnorepinephrine and (-)-erythro-alpha-methylepinephrine compete with high affinity for alpha-2 receptors, thereby supporting the suggestion that alpha-2 receptors mediate hypotensive effects of L-alpha-methyldopa . Furthermore, these metabolites of L-alpha-methyldopa competed with high potency for beta-1 receptors in forebrain and (-)-erythro-alpha-methylepinephrine was more potent than (-)-epinephrine, (-)-norepinephrine and (-)-erythro-alpha-methylnorepinephrine in competing for beta-2 receptors on human lymphocytes. These data suggest that beta receptor stimulation may be important in determining the net effects of L-alpha-methyldopa. L-alpha-Methyldopa metabolites were much less potent than (-)-epinephrine and (-)-norepinephrine in competition for alpha-1 receptors. (+/-)-alpha-Methyldopamine was less potent than other l-alpha-methyldopa metabolites at all three receptors, suggesting that it is unlikely to be an important hypotensive metabolite of L-alpha-methyldopa.
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008750:Methyldopa / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000378:metabolism*; D013237:Stereoisomerism
D002395:Catecholamines; D011941:Receptors, Adrenergic; D008750:Methyldopa; D003000:Clonidine