Pollack G M, Shen D D
J Pharmacol Methods. 1985 Apr;13(2):135-46. doi: 10.1016/0160-5402(85)90057-9.
A convulsive seizure model that utilizes timed intravenous infusions of pentylenetetrazol (PTZ) was developed to quantitate the magnitude of anticonvulsant effect in individual rats. PTZ was infused through an indwelling jugular vein catheter, and the threshold dose of PTZ was calculated from the time needed to produce clonic convulsions, the body weight of the animal, and the rate of infusion of the convulsant. The threshold dose of PTZ was determined in all animals 48 hr before and 15 min after anticonvulsant treatment. From theoretical considerations, the magnitude of anticonvulsant effect was defined as the logarithm of the posttreatment to pretreatment PTZ threshold dose ratio (log DR). The PTZ threshold was found to be insensitive to the rate of PTZ infusion and the body weight of the animal. Furthermore, the PTZ pretest did not influence the results of the posttest in animals treated with saline, and the interanimal variability in the PTZ threshold was found to be low (coefficient of variation of 12.2%). The PTZ infusion model was tested in a preliminary dose-response study of the anticonvulsant valproic acid (VPA). The ED50 for VPA determined with PTZ infusion technique (76.1 +/- 9.0 mg/kg) was in good agreement with a previous study that used the classical subcutaneous PTZ test. Since anticonvulsant effect is measured in individual, as opposed to groups, of animals, the PTZ infusion procedure may offer distinct advantages in the study of the pharmacodynamics of anticonvulsant compounds.
开发了一种利用戊四氮（PTZ）定时静脉输注的惊厥发作模型，以定量个体大鼠抗惊厥作用的强度。PTZ通过留置的颈静脉导管输注，PTZ的阈值剂量根据产生阵挛性惊厥所需的时间、动物体重和惊厥剂的输注速率来计算。在抗惊厥治疗前48小时和治疗后15分钟测定所有动物的PTZ阈值剂量。从理论考虑，抗惊厥作用的强度定义为治疗后与治疗前PTZ阈值剂量比的对数（log DR）。发现PTZ阈值对PTZ输注速率和动物体重不敏感。此外，PTZ预试验不影响用生理盐水治疗的动物的试验后结果，并且发现动物间PTZ阈值的变异性较低（变异系数为12.2%）。在抗惊厥药丙戊酸（VPA）的初步剂量反应研究中测试了PTZ输注模型。用PTZ输注技术测定的VPA的ED50（76.1±9.0mg/kg）与先前使用经典皮下PTZ试验的研究结果良好一致。由于抗惊厥作用是在个体动物而非动物群体中测量的，PTZ输注程序在抗惊厥化合物的药效学研究中可能具有明显优势。
