title: Desethylaprophen: a metabolite of aprophen with antimuscarinic activities.
abstract: The metabolic fate of aprophen hydrochloride (2-diethylaminoethyl 2,2-diphenylpropionate) was studied in rats after intravenous administration. Both 14C-labeled and unlabeled aprophen were used in these studies. Blood samples were collected and analyzed to determine the identities of the metabolites formed. Utilizing high-performance liquid chromatography, desethylaprophen was identified as a major metabolite in ether-extracted samples from rats, and could be detected in blood samples 1 min after intravenous administration. It was most likely formed by N-de-ethylation of aprophen by a cytochrome P-450-dependent monooxygenase. Synthetic desethylaprophen was found to possess cholinolytic activity (i.e., it functioned as a muscarinic antagonist by blocking the contraction of acetylcholine-stimulated guinea pig ileum, the release of alpha-amylase from pancreatic acinar cells stimulated by carbachol, and also by inhibiting the binding of [3H]N-methyl scopolamine to the muscarinic receptors of guinea pig ileum). It was interesting that although the biological effects of desethylaprophen were 100-fold lower than those of aprophen, it was equally able to compete for the binding sites of muscarinic receptors of the guinea pig ileum.
authors.affiliation: Department of Applied Biochemistry, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
authors.forename: N D
authors.initials: ND
authors.lastname: Brown
authors.forename: R M
authors.initials: RM
authors.lastname: Smejkal
authors.forename: E
authors.initials: E
authors.lastname: Breuer
authors.forename: B P
authors.initials: BP
authors.lastname: Doctor
authors.forename: P K
authors.initials: PK
authors.lastname: Chiang
mesh_terms: D000818:Animals; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D010276:Parasympatholytics; D010666:Phenylpropionates / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000378:metabolism; D000516:alpha-Amylases / Q000378:metabolism
chemical_list: D010276:Parasympatholytics; D010666:Phenylpropionates; D011976:Receptors, Muscarinic; C055647:desethylaprophen; D000516:alpha-Amylases; C006615:aprofen