Pharmacological characterization of dopamine-4-O-sulfate.

: Dopamine-4-O-sulfate (DA-4-S), a major metabolite of dopamine, was examined for pharmacologic activity both in vivo and in vitro. Intravenous doses of DA-4-S ranging from 1.3-34.3 micrograms/kg had no effect on renal blood flow or blood pressure in the anesthetized dog, demonstrating lack of agonist activity at vascular DA1 receptor sites. These data also suggest that DA-4-S is not metabolically converted to an active dopamine agonist in the dog. No beta-adrenoceptor agonist activity of DA-4-S could be detected in the isolated guinea-pig left atrium, and no alpha 1-agonist activity of DA-4-S could be detected in the perfused rabbit ear artery, although sympathetic neurotransmission was inhibited in this tissue at high concentrations (EC50 = 3.9 X 10(-6) M). This latter response was competitively inhibited by S-sulpiride. This lack of affinity for dopaminergic and adrenergic receptors was confirmed by biochemical assays (striatal adenylate cyclase stimulation; 3H-spiroperidol, 3H-clonidine, and 3H-WB 4101 binding using brain tissue preparations). In all the above tests, the activity of DA-4-S was much weaker than dopamine, showing this metabolite has little intrinsic dopaminergic or adrenergic pharmacological activity.