Central depressant effects of maltol analogs in mice.

Abstract

The central actions of maltol (2-methylpyromeconic acid, II), previously isolated from the extract of Passiflora incarnata, and its analogs were studied in mice. 2-Butyl-and 2-isobutylpyromeconic acid (IVd) were the most potent depressants of pentetrazoleinduced convulsion among the 2-alkylpyromeconic acids tested. The effect of 2-(1-hydroxy-isobutyl)pyromeconic acid (Vd) was more potent than that of IVd. Methylation on the 3-hydroxyl group of II or replacement of the O atom of the 4-pyrone ring with =NH did not alter the effect on pentetrazole-induced convulsion. Both IVd and Vd also showed depressing effects on the convulsion induced by strychnine or picrotoxin but did not affect the convulsion induced by caffeine. The anticonvulsive effects of IVd and Vd on the maximal electroshock seizure were less potent than that of 2-ethylpyromeconic acid (III). II, III, IVd and Vd depressed spontaneous motor activity, and III and Vd prolonged the hexobarbital-induced sleeping time. The brain levels of these four compounds after subcutaneous injection in mice were not related to their lipid solubilities.