Anticonvulsant activity of the nipecotic acid ester, (±)-m-nitrophenyl-3-piperidinecarboxylate

The nipecotic acid ester, (±)-m-nitrophenyl-3-piperidinecarboxylate hydrochloride (MNPC) is a potent inhibitor of uptake of GABA in vitro and should be able to penetrate into the brain much more readily than the parent compound nipecotic acid. A study of the effects of MNPC on convulsions induced by chemicals which interfere with GABA-mediated neurotransmission was carried out in the mouse, with MNPC being administered by subcutaneous injection 30, 60 or 90 min prior to challenge with bicuculline. It was found that MNPC protected against convulsions induced by bicuculline with ED₅₀ values for clonic and tonic convulsions of 157.8 and 138.8 mg kg, respectively, at the time of peak effect of 60 min and MNPC abolished both the clonic and tonic components of isoniazid convulsions with respective ED₅₀ values of 255.3 and 76.7 mg kg at 1 hr. Picrotoxin and pentylenetetrazol-induced seizures were also blocked with corresponding ED₅₀ values for clonic convulsions of 224.9 and 235.9 mg kg at 1 hr. No serious side effects were observed during the 90 min period after the administration of MNPC in doses up to 600 mg kg.