Evaluation of the cholinergic and adrenergic effects of two tropane alkaloids from Erythroxylum pervillei

Pervilleine A is an aromatic ester tropane alkaloid from Erythroxylum pervillei that has shown promising activity as a multidrug resistance inhibitor. Due to its structural similarity with the well known (‐)‐hyoscyamine and (‐)‐cocaine, the cholinergic and adrenergic activities of pervilleine A were evaluated. At 30 µ m (±)‐pervilleine A hydrochloride exhibited non‐competitive inhibition of the cholinergic response in the guinea‐pig ileum and did not affect the carbachol‐induced contraction of the rat anococcygeus smooth muscle. (±)‐Pervilleine A hydrochloride blocked nonspecifically the vascular response of (‐)‐norepinephrine in the rat aorta ring, while the contractile response of rat vas deferens to (‐)‐norepinephrine was not affected significantly at a 100 µ m concentration. An analogue of pervilleine A, (±)‐pervilleine H, without a 6‐ O ‐ trans ‐3,4,5‐trimethoxycinnamoyl ester substituent required for anti‐multidrug resistance activity, did not exhibit any effects in these experiments. The data suggest that (±)‐pervilleine A hydrochloride has weak nonspecific anticholinergic and vascular antiadrenergic activities. The lack of significant cholinergic and adrenergic receptor‐mediated activities may be considered advantageous for the further development of pervilleine A as a new adjuvant in cancer chemotherapy. Copyright © 2007 John Wiley & Sons, Ltd.