Dopamine receptors: structure-activity relationship of d-tubocurarine analogues

d-Tubocurarine (dTC) and d-tubocurine acted as antagonists of the dopamine-induced inhibition of adrenergic neurotransmission in the isolated, perfused rabbit ear artery. N-Methyl-dTC and O,O,N-trimethyl-dTC (metocurine) did not exhibit dopaminergic antagonist activity. dTC contains one tertiary (3 degrees) nitrogen and one quaternary (4 degrees) nitrogen and d-tubocurine contains two 3 degrees nitrogens; whereas, both N-methyl-dTC and O,O,N-trimethyl-dTC have two 4 degrees nitrogens. The results suggest that a dTC analogue (e.g., metocurine) which lacks a 3 degrees nitrogen should be considered for use in patients treated with dopamine.