George B, Kulkarni S K
Pharmacology Division, Panjab University, Chandigarh, India.
Methods Find Exp Clin Pharmacol. 1998 Jun;20(5):395-401. doi: 10.1358/mf.1998.20.5.485700.
The atypical antipsychotic clozapine treatment (at high doses) has been reported to be associated with tremors. However, antitremor effects of clozapine have also been reported in Parkinsonian patients. Recently, we reported the protective effects of acute clozapine against pilocarpine-induced status epilepticus (SE). With this background, this study was designed to investigate the possible protective effect of clozapine against acute chemoconvulsions and kindling seizures produced by pentylenetetrazol (PTZ) in mice. Various doses of clozapine (1.0, 2.5, 5.0 and 7.5 mg) offered different degrees of protective effects against PTZ (80 mg) challenge, and the maximum protection was observed with the 2.5 mg dose as it delayed the onset of jerks, clonus, tonic extensor phase and reduced mortality. Animals chronically pretreated with clozapine (2.5, 7.5 and 15.0 mg) for 8 days when challenged by PTZ (50 and 80 mg) on the 8th day also showed protection. Repeated administration of PTZ at a subconvulsive dose (30 mg/kg, i.p, three times a week, for 9 weeks) produced kindled seizures in over 80% of the mice. Pretreatment with clozapine (1 or 5 mg) prevented the behavioral manifestations (motor seizures) as well as the development of kindling. The effect was compared with GABA (200 mg) and diazepam (1 mg), a known anticonvulsant drug.
据报道，非典型抗精神病药物氯氮平治疗（高剂量）与震颤有关。然而，也有报道称氯氮平对帕金森病患者有抗震颤作用。最近，我们报道了急性氯氮平对毛果芸香碱诱导的癫痫持续状态（SE）的保护作用。在此背景下，本研究旨在探讨氯氮平对小鼠戊四氮（PTZ）诱发的急性化学惊厥和点燃性癫痫发作的可能保护作用。不同剂量的氯氮平（1.0、2.5、5.0和7.5毫克）对PTZ（80毫克）激发提供了不同程度的保护作用，其中2.5毫克剂量的保护作用最大，因为它延迟了抽搐、阵挛、强直性伸展期的发作并降低了死亡率。在第8天用氯氮平（2.5、7.5和15.0毫克）慢性预处理8天的动物，在受到PTZ（50和80毫克）攻击时也显示出保护作用。以亚惊厥剂量（30毫克/千克，腹腔注射，每周三次，共9周）重复给予PTZ，在超过80%的小鼠中产生了点燃性癫痫发作。用氯氮平（1或5毫克）预处理可预防行为表现（运动性癫痫发作）以及点燃的发展。将该效果与已知的抗惊厥药物GABA（200毫克）和地西泮（1毫克）进行了比较。
