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-tetrahydronaphthalene (ADTN) were screened for dopamine vascular agonist activity. Effects of intraarterial 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 DDTN 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 micrograms/kg; whereas, the threshold dose of DA is 4--8 micrograms/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.