title: Ionization constants, octanol partition coefficients and cholinesterase inhibitor constants for chlorpromazine and its metabolites.
abstract: The relationship between the lipophilic character of chlorpromazine and seven of its metabolites and their ability to inhibit horse serum cholinesterase (Ki) has been investigated. Log(1/Ki) values were correlated with log P octanol partition coefficients (r = 0.88, P less than 0.01, n = 8). The inhibitor values ranged from 2.7 x 10(-6) M for chlorpromazine to 48.6 x 10(-6) M for monodesmethylchlorpromazine sulphoxide. Ionization constants were determined by limiting solubility, spectrophotometry and pH-partition characteristics. Demethylated metabolites were more basic than the tertiary amines and the sulphoxides were slightly less basic than the corresponding sulphides.
authors.affiliation: Department of Pharmacology, London Hospital Medical College, UK.
authors.forename: R
authors.initials: R
authors.lastname: Whelpton
mesh_terms: D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002746:Chlorpromazine / Q000008:administration & dosage / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors; D003124:Colorimetry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D000442:Octanols; D012995:Solubility
chemical_list: D002800:Cholinesterase Inhibitors; D000442:Octanols; D002746:Chlorpromazine