Inhibition of the sympathetic nervous system by a series of heterocyclic congeners of dopamine

Abstract

A series of heterocyclic congeners of dopamine (GJH-series) with different positions of phenolic oxygens and with the possibility of cis and trans isomerism at the 4a-10b ring juncture was evaluated in vitro and in vivo for dopaminergic activity. Two compounds, GJH-166 and GJH-171, were found to suppress the positive chronotropic response induced by stimulation of the right cardioaccelerator nerves. These effects were antagonized by haloperidol. GJH-166, in doses as low as 9.5 x 10(-4) mugmol/kg reduced the resting heart rate in cats anesthetized with alpha-chloralose. GJH-166 and GJH-171 antagonized pressor responses induced by bilateral carotid occlusion and stimulation of the central stump of the sciatic nerve. The results outlined in this manuscript support the hypothesis that the extended conformation of the dihydroxyhenylethylamine moiety of dopamine with a trans isomeric form is favorable for dopaminergic agonist activity.