Esters of nipecotic and isonipecotic acids as potential anticonvulsants

Article abstract of DOI:10.1002/jps.2600711108

A variety of esters of nipecotic and isonipecotic acids were synthesized and evaluated for anticonvulsant activity. The ester group was varied in terms of lipophilicity and reactivity toward hydrolysis. The esters were screened against seizures induced by electroshock, pentylenetetrazol, and the putative γ-aminobutyric acid antagonist, bicuculline. The most significant activity was demonstrated by the p-nitrophenyl esters of nipecotic and isonipecotic acids against bicuculline-induced seizures. Esters of nipecotic acid were tested for in vitro inhibition of γ-aminobutyric acid and L-proline uptakes into mouse whole brain minislices. The p-nitrophenyl, n-octyl, and succinimidyl esters were the most potent inhibitors of γ-aminobutyric acid uptake. The uptake of γ-aminobutyric acid by the ester derivatives appeared to involve specific and nonspecific mechanisms.