Inhibition of canine adrenergic transmission by an analog of dopamine: GJH-166.

Experiments were conducted to investigate the effect of GJH-166 [Trans-4-methyl-7,8-dihydroxy-1,2,3,4,4a,5,6,10b-octahydrobenzo (f) quinoline HBr], a potential dopamine agonist, on responses to adrenergic vasoconstrictor stimuli in dogs. The hindlimb, gracilis muscle and spleen were isolated and perfused with arterial blood at constant flows. Responses of the nictitating membrane to adrenergic stimuli were aso studied. Intravenous injections of GJH-166 in doses of 0.25 to 4.00 micron/kg impaired responses to sympathetic nerve stimulation of the perfused hindlimb, gacilis muscle and spleen, and also inhibited responses of the nictitating membrane. GJH-166 had a preferential inhibitory effect on responses induced by low frequency stimulation of nerves. Haloperidol antagonized the inhibitory effect of GJH-166 on sympathetic transmission. The changes induced by norepinephrine at the perfused sites were not affected by the compound. Pressor responses to norepinephrine and tyramine were not inhibited by GJH-166. As a result of this study, the suggestion has been made that GJH-166 impairs sympathetic transmission by acting on certain inhibitory dopaminergic receptors located on the adrenergic nerve terminals.