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Inhibition of Uptake 1 by dopexamine hydrochloride in vitro )
Author(s) -
Mitchell Paul D.,
Smith George W.,
Wells Edward,
West Philip A.
Publication year - 1987
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1987.tb11320.x
Subject(s) - reserpine , hydrochloride , chemistry , dopamine , pharmacology , isoprenaline , chronotropic , dobutamine , inotrope , norepinephrine , medicine , agonist , long term potentiation , endocrinology , stimulation , heart rate , receptor , biochemistry , hemodynamics , blood pressure
1 Dopexamine hydrochloride, a compound under evaluation for the acute treatment of heart failure, was examined in vitro for its ability to prevent neuronal uptake of noradrenaline. 2 Despite possessing only weak β 1 ‐adrenoceptor agonist activity in paced guinea‐pig left atria, dopexamine hydrochloride was only 23 times less potent than isoprenaline in augmenting responses of field‐stimulated atrial preparations. 3 This potent effect was not observed in field‐stimulated atria depleted of noradrenaline by reserpine and in the presence of cocaine was greatly reduced (1 μ m ) or abolished (50 μ m ). 4 Dopexamine hydrochloride (3 μ m ) potentiated the inotropic effect of exogenous noradrenaline in paced atria, thereby resembling cocaine (10 μ m ) and dopamine (30 μ m ), both of which are known inhibitors of Uptake 1 . 5 The sodium‐dependent uptake of [ 3 H]‐noradrenaline into rabbit brain synaptosomes was prevented by dopexamine hydrochloride (IC 50 26 n m ) and cocaine (IC 50 108 n m ), as well as by two other catecholamines used in the treatment of heart failure, dopamine (IC 50 270 n m ) and dobutamine (IC 50 380 n m ). 6 The cardiac stimulant effect of dopexamine hydrochloride reported in dogs and in patients with heart failure, may therefore be due in part to potentiation of endogenous catecholamines.