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N-氨甲基哌嗪-3,3-二乙基-2,4-吡啶二酮的抗惊厥活性与已知抗癫痫药物活性的比较研究。

Comparative study of the anticonvulsive activity of N-aminomethylpiperazine-3,3-diethyl 2,4-pyridinedione with the activity of known antiepileptic agents.

作者信息

Belcheva I, Stoytchev T, Alov P

出版信息

Acta Physiol Pharmacol Bulg. 1984;10(1):59-63.

PMID:6741565
Abstract

N-aminomethylpiperazine-3,3-diethyl-2,4-pyridinedione (DKMP) is a newly synthesized compound with a marked anticonvulsive effect in various epileptic models. The aim of the present work is to compare its anticonvulsive effect in corazol convulsions (100 mg/kg corazol, s.c.) with known anticonvulsants applied in clinical practice. The compounds tested were applied subcutaneously in equitoxic doses (1/20 and 1/30 of their respective LD50). Some undesirable side effects of the antiepileptic agents tested were also studied. With the experimental model used, DKMP was found to have a better anticonvulsive effect compared with diphenylhydantoin, depakin, suxilep and phenobarbital. Diazepam completely inhibited the convulsions, but it has an undesirable strong myorelaxing effect. In a subchronical experiment it was found that no tolerance developed toward DKMP, while the anticonvulsant effect of diazepam significantly decreased on the 15th day, compared with a single administration. Using the rota-rod test it was found that the agents studied had a stronger neurotoxic action compared with DKMP. These results outline DKMP as a promising compound with good antiepileptic activity, comparable to that of the known anticonvulsants.

摘要

N-氨甲基哌嗪-3,3-二乙基-2,4-吡啶二酮(DKMP)是一种新合成的化合物,在各种癫痫模型中具有显著的抗惊厥作用。本研究的目的是将其在戊四氮惊厥(100mg/kg戊四氮,皮下注射)中的抗惊厥作用与临床实践中应用的已知抗惊厥药物进行比较。所测试的化合物以等效毒性剂量(各自LD50的1/20和1/30)皮下给药。还研究了所测试的抗癫痫药物的一些不良副作用。在所使用的实验模型中,发现DKMP与苯妥英、丙戊酸钠、舒噻美和苯巴比妥相比具有更好的抗惊厥作用。地西泮完全抑制惊厥,但具有不良的强烈肌松作用。在一个亚慢性实验中发现,对DKMP未产生耐受性,而与单次给药相比,地西泮的抗惊厥作用在第15天显著降低。使用转棒试验发现,与DKMP相比,所研究的药物具有更强的神经毒性作用。这些结果表明DKMP是一种有前景的化合物,具有良好的抗癫痫活性,与已知的抗惊厥药物相当。

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