[Pharmacologic study of dopamine catabolites on the contractility of isolated guinea pig myocardium].

Tetrahydroisoquinolines (TIQs) are alkaloids originated as natural catabolic derivatives of catecholamines (CAT). Dopamine, under special circumstances, condenses with aldehydes to produce tetrahydropapaveroline (THP), salsolinol (SOL) and salsoline (SAL). We investigated the inotropic activity of THP, SOL and SAL on the isometric contractility of papillary muscles isolated from guinea pigs hearts and compared their actions to those corresponding to adrenaline (A) and isopropylarterenol (ISO). In order to analyze their combined effects, TIQs and A were applied simultaneously. THP, SOL and SAL produced positive inotropic effects as beta receptor agonists; their actions were antagonized with propranolol. The inotropic efficacy of TIQs compared to that of catecholamines, is: CAT = 1; SAL = 0.32; THP = 0.47 and SOL = 0.32. Their middle effective dose (DE50), indicates an order of potency of: ISO = SAL greater than A = THP greater than SOL. Combination of THP or ISO with A produces an additive effect; however, SAL behaves as a partial agonist, meaning that it produces an antagonistic, non-competitive type effect on the inotropic action of adrenaline. Chemical structure of TIQs shows significant relationship with their pharmacological activity on ventricular myocardium, similar to that of catecholamines. The influence of the methoxyl group attached to C-7 in SAL, as the only difference with SOL which instead has a hydroxyl group in that position, deserves special mention; such structural difference provides to SAL bigger inotropic efficacy and potency, as well as beta adrenergic antagonistic activity. The results of the present paper emphasize the biological significance of active catabolites from catecholamines as are the tetrahydroisoquinoline compounds.