title: Evaluation of the cholinergic and adrenergic effects of two tropane alkaloids from Erythroxylum pervillei.
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.
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Young-Won
authors.initials: YW
authors.lastname: Chin
authors.forename: A Douglas
authors.initials: AD
authors.lastname: Kinghorn
authors.forename: Popat N
authors.initials: PN
authors.lastname: Patil
mesh_terms: D018663:Adrenergic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D018678:Cholinergic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology; D030921:Erythroxylaceae / Q000737:chemistry*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D014326:Tropanes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014649:Vas Deferens / Q000187:drug effects
chemical_list: D018663:Adrenergic Agents; D000316:Adrenergic alpha-Agonists; D000470:Alkaloids; D018678:Cholinergic Agents; D018679:Cholinergic Agonists; D014326:Tropanes; C428023:pervilleine A; C510042:pervilleine H; D002217:Carbachol; D009638:Norepinephrine