The Protective Effect of Chlorpromazine on Pentylenetetrazole Induced Seizure

ABSTRACT

PURPOSE: Chlorpromazine(CPZ) is known to inhibit glutamate dehydrogenase(GDH). Reductive amination of alpha-ketoglutarate is catalyzed by GDH and forms glutamate, a major excitatory neurotransmitter. Thus, we hypothesized that CPZ might have a seizure-protective effect by inhibition of glutamate release from the excitatory presynaptic nerve terminal. The present study was designed to investigate the protective effect of CPZ on pentylenetetrazole(PTZ)-induced seizure in rats. METHODS: Twenty male Sprague-Dawley rats were equally divided into 2 groups. CPZ(20 mg/kg) was administered to experimental animals by subcutaneous injection, while normal saline to control animals. Twenty minutes later, seizures were chemically induced by intraperitoneal injection of PTZ(60 mg/kg). Seizure severity was evaluated by using a scoring system of seizure behaviors0, no seizure; 0.5, abnormal behavior; 1, myoclonic jerk; 2, myoclonic jerk with jumping; 3, forelimb clonus with preserving righting reflex; 4, generalized clonic seizure with brief loss of righting reflex; 5, generalized tonic clonic seizure; 6, expire. A greater score represents a more severe seizure. RESULTS: The seizure behavior scores(2.8+/-0.2) in the experimental group were significantly lower than those(3.9+/-0.4) in the control group(P<0.05). CONCLUSION: This study demonstrates that CPZ decrease PTZ-induced seizure severity in rats. Our results suggest that CPZ may have a seizure-protective effect. We hope that further studies on this issue should be performed in near future.