Evaluation of the cholinergic and adrenergic effects of two tropane alkaloids from Erythroxylum pervillei |
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Authors: | Chin Young-Won Kinghorn A Douglas Patil Popat N |
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Affiliation: | Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA. |
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Abstract: | 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 microm (+/-)-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 microm 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. |
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Keywords: | (±)‐pervilleine A HCl (±)‐pervilleine H tropane aromatic ester alkaloids anticholinergic activity antiadrenergic activity |
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