Influence of some β-adrenoceptor antagonists on the anticonvulsant potency of antiepileptic drugs against audiogenic seizures in DBA/2 mice
Influence of some β-adrenoceptor antagonists on the anticonvulsant potency of antiepileptic drugs against audiogenic seizures in DBA/2 mice
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DOI：
10.1016/s0014-2999(02)01536-4
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发表时间：
2002-05-10
影响因子：
5
通讯作者：
Fischer, W
中科院分区：
文献类型：
--
作者：
De Sarro, G;Di Paola, ED;Fischer, W
普萘洛尔的两种对映体拮抗DBA/2小鼠全身强直-阵挛性癫痫发作，其中（-）-对映体的效力约为（+）-对映体的1.5倍。美托洛尔活性较低，阿替洛尔不能影响听源性癫痫发作。与常规抗癫痫药物联合使用时，在不影响听源性癫痫发作发生率的剂量下试验的普萘洛尔对映体均增加了地西泮、苯巴比妥、丙戊酸盐和拉莫三嗪的抗惊厥活性，并倾向于增加卡马西平和苯妥英的抗惊厥活性。（-）-对映体的作用更明显，这种增加与运动障碍的增强有关，然而，抗癫痫药物与普萘洛尔对映体的联合治疗的治疗指数比单独与生理盐水的联合治疗更有利，美托洛尔也能够降低抗癫痫药物的ED 50值，而阿替洛尔显示无作用。由于普萘洛尔对映体均未显著影响抗癫痫药的总血浆和游离血浆水平，因此不太可能存在药代动力学相互作用。此外，（+）-和（-）-普萘洛尔并没有显着影响降温效果的抗癫痫药测试。总之，普萘洛尔和美托洛尔的两种对映体与一些常规抗癫痫药物（最显著的是地西泮、苯巴比妥、拉莫三嗪和丙戊酸盐）联合给药时显示出相加的抗惊厥作用，表明此类药物联合给药可能具有治疗相关性。(C)2002 Elsevier Science B. V.保留所有权利。
The two enantiomers of propranolol antagonize generalized tonic-clonic seizures in DBA/2 mice with the (-)-enantiomer being about 1.5 times more potent than the (+)-enantiorner. Metoprolol was less active and atenolol was unable to affect audiogenic seizures. In combination with conventional antiepileptic drugs, both propranolol enantiomers tested in doses not affecting the occurrence of audiogenic seizures increased the anticonvulsant activity of diazepam, phenobarbital, valproate and lamotrigine and tended to increase that of carbamazepine and phenytoin. The effect was more pronounced with the (-)-enantiomer, This increase was associated with an enhancement of motor impairment, however, the therapeutic index of combined treatment of the antiepileptic drugs with both propranolol enantiomers was more favourable than the combination with saline alone, Metoprolol was also able to decrease the ED50 values of the antiepileptic drugs, whereas atenolol showed no effects. Since neither enantiomer of propranolol significantly influenced the total and free plasma levels of the antiepileptics, pharmacokinetic interactions are not likely. In addition, (+)- and (-)-propranolol did not significantly affect the hypothermic effects of the antiepileptics tested. In conclusion, both enantiomers of propranolol and metoprolol showed an additive anticonvulsant effect when co-administered with some conventional antiepileptic drugs, most notably diazepam, phenobarbital, lamotrigine and valproate, implicating a possible therapeutic relevance of such drug combinations. (C) 2002 Elsevier Science B.V. All rights reserved.