Reference

Competitive binding between cocaine and various drugs to synthetic levodopa melanin

Competitive binding between cocaine and various drugs to synthetic levodopa melanin. Baweja, R.; Sokoloski, T. D.; Patil, P. N. (Coll. Pharm., Ohio State Univ., Columbus, Ohio, USA). J. Pharm. Sci., 66(11), 1544-7 (English) 1977. CODEN: JPMSAE. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacodynamics) The interaction of 15 drugs with synthetic levodopa melanin was studied by measuring their relative tendency to compete with 14C-labeled (±)-cocaine-HCl (I-HCl) [56222-58-3] for sites on the polymer. The binding of I to melanin followed a Type I Langmuir adsorption isotherm in the absence of added drugs. I in the presence of a ninefold greater concn. of (+)-norepinephrine(+)-bitartrate [51-40-1], levarterenol [51-41-2], dextroamphetamine sulfate [51-63-8], levamfetamine sulfate [1508-75-4], (-)-ephedrine-HCl [50-98-6], dopamine-HCl [62-31-7], cyclopentolate-HCl [5870-29-1], tropicamide [51-62-7], and perhaps, desipramine-HCl [58-28-6] conformed to a Type I adsorption relationship modified to account for competitive binding. Reciprocal plots for the binding of I in the presence of these drugs permit a comparison of their relative affinities to melanin. Chlorpromazine [50-53-3], promazine-HCl [53-60-1], fluphenazine [69-23-8], thioridazine-HCl [130-61-0], imipramine-HCl [113-52-0], and chloroquine diphosphate [50-63-5] in ratios of 9:1 (drug-I) gave results that are not explainable by a model based on competitive inhibition of I binding. However, studies at ratios of 1:1 for promazine and of 0. and 1:1 for chloroquine showed conformity with the competitive inhibition model, so affinities could be compared. The behavior of I in the presence of thioridazine even at a 1:1 ratio cannot be judged as competitive inhibition. The overall results showed that the relative binding found was: some phenothiazines u chloroquine > cyclopentolate > tropicamide > sympathomimetic amines.