Neuroinhibitory Effects of SK&F 85174, a Novel Dopamine Receptor Agonist

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Abstract
SK and F 85174 (3-allyl-6-chloro-2,3-4,5-tetrahydro-1-(4-hydroxyphenyl)-1H-3-benzazepine-7,8-diol methanesulfonate) the N-allyl derivative of SK and F 82526, a selective postjunctional dopaminergic agonist, retains the potent agonist activity of the parent molecule at the postjunctional dopamine receptor, as evidenced by activation of the dopamine-sensitive adenylate cyclase in rat caudate homogenates (EC50 [concentration giving 50% effectiveness] = 11 nM). Unlike SK and F 82526, SK and F 85174 is a potent inhibitor of adrenergic neurotransmission. This neuroinhibitory effect can be demonstrated both in isolated vascular preparations, and in in situ preparations in the anesthetized dog measuring both cardiac and vascular neurotransmission. In each of these preparations, the effect of SK and F 85174 can be blocked by the dopamine receptor antagonists, metoclopramide, or 1-sulpiride, showing that its action occurs via activation of prejunctional dopamine receptors. Inhibition of the responses to sympathetic nervous system activation, when combined with the ability to increase renal blood flow by stimulation of postjunctional dopamine receptors, could make SK and F 85174 an effective therapeutic agent for a variety of cardiovascular disorders, including angina pectoris, hypertension and congestive heart failure.