The Protective Effect of Chlorpromazine on Flurothyl-Induced Seizure / 대한소아신경학회지

ABSTRACT

PURPOSE: Chlorpromazine(CPZ) is known to inhibit glutamate ehydrogenase(GDH). Reductive amination of alpha-ketoglutarate is catalyzed by GDH and forms glutamate, a major excitatory neurotransmitter. Thus, I hypothesized that CPZ might have a seizure- protective effect by inhibiting glutamate release from the excitatory presynaptic nerve terminal. The present study was designed to investigate the protective effect of CPZ on flurothyl-induced seizure in rats. METHODS: Twenty-eight 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 flurothyl infusion(40 microL/min). Seizure susceptibility was defined as the latency from the start of flurothyl infusion to the onset of a generalized seizure(loss of posture with bilateral hindlimb tonic extension). Shorter latency reflects greater seizure susceptibility. RESULTS: The mean(+/-SEM) seizure latency in the experimental group was 539.2 (+/-17.5) seconds, and it was significantly longer than 432.4(+/-21.9) seconds in the control group(P<0.001). CONCLUSION: This study demonstrates that CPZ decrease flurothyl-induced seizure susceptibility in rats. This result suggests that CPZ may have a seizure-protective effect. I hope that further studies on this issue should be performed in a near future.