Chambon J P, Brochard J, Hallot A, Heaulme M, Brodin R, Roncucci R, Biziere K
J Pharmacol Exp Ther. 1985 Jun;233(3):836-44.
CM 40907 [3-(4-hydroxypiperidyl)-6-(2'-chlorophenyl)-pyridazine] is a chemically original compound which possesses the pharmacological properties of a potent, p.o. active anticonvulsant. The anticonvulsant activity of CM 40907 was examined in mice, rats and photosensitive Papio-papio baboons and compared to that of phenobarbital, diphenylhydantoin, carbamazepine, sodium valproate and ethosuximide. In mice, CM 40907 antagonized electroconvulsive shock and chemically induced seizures with an overall potency comparable to that of carbamazepine and a therapeutic ratio (ED50 rotorod/ED50 electroshock) superior to that of ethosuximide, sodium valproate, phenobarbital and carbamazepine. In the rat CM 40907 suppressed completed kindled amygdaloid seizures and was approximately as active as phenobarbital. In naturally photosensitive Senegalese Papio-papio baboons CM 40907 antagonized myoclonus and cortical paroxysmal discharges. In this model CM 40907 was approximately one-fourth as potent as phenobarbital, twice as potent as carbamazepine and 6 times more potent than sodium valproate. In mice CM 40907, at anticonvulsant doses, increased the affinity of [3H]flunitrazepam for its central receptor site. Based on these results it is postulated that CM 40907 is a potent and relatively nonsedative anticonvulsant and may be of therapeutic benefit in epileptic disorders.
CM 40907 [3-(4-羟基哌啶基)-6-(2'-氯苯基)-哒嗪] 是一种化学结构新颖的化合物，具有强效口服活性抗惊厥药的药理特性。在小鼠、大鼠和光敏性狒狒中检测了CM 40907的抗惊厥活性，并与苯巴比妥、苯妥英钠、卡马西平、丙戊酸钠和乙琥胺进行了比较。在小鼠中，CM 40907拮抗电休克惊厥和化学诱导的惊厥，其总体效力与卡马西平相当，治疗指数（ED50转棒试验/ED50电休克）优于乙琥胺、丙戊酸钠、苯巴比妥和卡马西平。在大鼠中，CM 40907抑制完全点燃的杏仁核惊厥，活性与苯巴比妥大致相当。在天然光敏的塞内加尔狒狒中，CM 40907拮抗肌阵挛和皮质阵发性放电。在该模型中，CM 40907的效力约为苯巴比妥的四分之一，是卡马西平的两倍，比丙戊酸钠强6倍。在小鼠中，抗惊厥剂量的CM 40907增加了[3H]氟硝西泮对其中枢受体位点的亲和力。基于这些结果，推测CM 40907是一种强效且相对无镇静作用的抗惊厥药，可能对癫痫疾病具有治疗益处。
