DOPAMINE VASCULAR ACTIONS OF N-SUBSTITUTED DERIVATIVES OF 2-AMINO-6,7-DIHYDROXY-1,2,3,4-TETRAHYDRONAPHTHALENE (ADTN)

N-ethyl, N-n-propyl, N-n-butyl, N,N-di-n-propyl and N-n-propyl-N-n-butyl derivatives of 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphahalene (ADTN) were screened for dopamine vascular agonist activity. Effects of intra-arterial injections of the drugs on renal and femoral blood flow were measured in pentobarbital-anesthetized dogs before and after phenoxybenzamine (POB), 5-10 mg/kg. All ADTN derivatives were more potent vasoconstrictors than dopamine (DA) before POB. The di-substituted analogs were approximately 1 4 and the mono-substituted derivatives were about 1 16 as active as norepinephrine as vasoconstrictors. After POB the two di-substituted analogs were about 1 4 as active as DA in causing renal vasodilation. The three mono-substituted analogs produced relatively minor and inconsistent effects on renal blood flow, and were more than 100 times less effective than DA as vasodilators. The two di-substituted analogs markedly increased blood pressure with little effect on cardiac contractility in doses up to 32 μg/kg; whereas, the threshold dose of DA is 4-8 μg/kg. This and our previous results show that structure activity relationships of DA and ADTN, a semi-rigid analog of DA, are similar. However, the rigid analogs tend to be more potent vasoconstrictors than their flexible chain homologs. © 1979.