Kinetics of Solvolysis and Muscarinic Actions of an N-Methyl-N-(2-bromoethyl)amino Analogue of Oxotremorine

Article abstract of DOI:10.1021/jm00388a018

An N-methyl-N-(2-bromoethyl)amino analogue (2) of oxotremorine cyclized in phosphate buffer to an aziridinium ion (3).The first-order rate constants (k₁) for the cyclization reaction at 22 and 37 deg C (pH 7.3) were 0.14 and 0.85 min^-1, respectively.Determination of k₁ as a function of pH gave a pK_a value of 5.6 for 2.The rate constants (k₂) for the hydrolysis of 3 at 22 and 37 deg C (pH 7.3) were 0.0083 and 0.040 min^-1, respectively.Compound 3 was 3-fold more active than oxotremorine as a muscarinic agonist on the guinea pig ileum, whereas its nicotinic actions, as estimated on the frog rectus, were quite weak.Because of its greater rate of cyclization and the higher peak concentrations of the aziridinium ion which ensue, 2 may offer advantages over its (2-chloroethyl)amino analogue (1) as an alkylating ligand for muscarinic receptors.