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SK&F 89124, A POTENT AND SELECTIVE AGONIST AT PREJUNCTIONAL DOPAMINE RECEPTORS
Author(s) -
HIEBLE J.P.,
SULPIZIO A.C.,
SARAU H.M.,
FLAIM K.E.,
BLUMBERG A.L.,
McCAFFERTY J.P.,
ZEID R.L.
Publication year - 1989
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1989.tb00464.x
Subject(s) - agonist , medicine , endocrinology , receptor , stimulation , chemistry , dopamine receptor , biology
Summary— SK&F 89124 (4‐[2‐( N,N‐di‐n ‐propylamino)ethyl]‐7‐hydroxy‐2(3 H ) indolone) can be considered as a derivative of N,N ‐di‐ n ‐propyldopamine (DPDA) in which the meta ‐hydroxyl is replaced by a cyclic amide function. SK&F 89124 is at least one order of magnitude more potent than DPDA as an agonist at peripheral inhibitory prejunctional dopamine receptors (DA 2 receptors) in the isolated perfused rabbit ear artery. A potent agonist action of SK&F 89124 at the DA 2 receptor can also be demonstrated by inhibition of radioactive overflow from prelabelled canine coronary artery or saphenous vein, and in the anesthetized dog as an inhibition of the tachycardia induced by cardioaccelerator nerve stimulation or the increase in hind‐limb perfusion pressure induced by stimulation of the lumbar sympathetic chain. SK&F 89124 is a potent inhibitor of the binding of [ 3 H]spiroperidol to D 2 receptors in bovine pituitary homogenates. High concentrations of SK&F 89124 do not activate the adenylate cyclase D 1 receptor in rat caudate homogenates, nor produce activation of α 2 ‐adrenoceptors or H 2 ‐histamine receptors in the guinea pig atrium. Although some α 1 ‐adrenoceptor mediated vasoconstriction is produced in the rabbit ear artery and rabbit aorta, the concentrations required are several orders of magnitude higher than those active at the DA 2 receptor. From these data it is evident that this structural modification can increase both the potency and selectivity of DPDA as a DA 2 receptor agonist. The potency and selectivity of SK&F 89124 make this agent a useful tool for determination of the functional role of the DA 2 receptor.