Renal Elimination of 3-Methylaminoisocamphane Hydrochloride (Mecamylamine)

Abstract

Mecamylamine, 3-methylaminoisocamphane hydrochloride, a secondary amine with a pka of 11.4, can be both actively secreted and actively reabsorbed by the renal tubules in the dog. Net secretion occurs when the urine is acid; net reabsorption occurs when the urine is alkaline. A direct renal extraction study showed that tubular secretion occurred at rates equal to effective renal plasma flow. No self-depression of tubular secretion was observed at increased loads. The clearance of mecamylamine was depressed below glomerular filtration rate when the urine became alkaline, whether or not a systemic alkalosis existed. In some experiments, the clearance was as low as 3 ml/min., corresponding to reabsorption of more than 90% of the filtered drug. The secretory mechanism is not identical with that for p-aminohippurate. Approximately one-fourth of an administered dose of mecamylamine is excreted in the urine within 24 hours, whether the drug is given orally or parenterally. These data are consistent with the biological evidence that absorption from the gastrointestinal tract is essentially complete, and that extrarenal factors are important in the over-all physiological economy of the drug.