Department of Experimental and Clinical Pharmacology, Medical University, Lublin of Lublin, Poland.
Department of Nephrology, Medical University of Lublin, Lublin, Poland.
Pharmacol Rep. 2019 Jun;71(3):466-472. doi: 10.1016/j.pharep.2019.02.003. Epub 2019 Feb 8.
β-Adrenergic receptor agonists are widely used agents in the treatment of asthma or preterm labor. Since prevalence of asthma was shown to be higher in patients with epilepsy and modulation of noradrenergic system activity may modify epilepsy course, the aim of the present study was to examine the effect of salbutamol (SALB), one of the most commonly used β-adrenergic receptor agonist on the anticonvulsant potency of four classical antiepileptic drugs (AEDs): valproate (VPA), carbamazepine (CBZ), phenytoin (DPH) and phenobarbital (PB) in mice subjected to the maximal electroshock (MES)-induced seizures.
Seizures were caused by a current delivered through ear-clip electrodes. The influence of AEDs and SALB on animals' motor coordination and memory processes was also evaluated.
Single SALB injection did not change, whereas 7 days SALB administration decreased seizure threshold in the MES-induced seizures in mice. Moreover, SALB injected ip for 1 day and for 7 days lowered the antiepileptic activity of PB in the MES-induced seizures in mice, but did not change the effect of other analyzed AEDs: VPA, CBZ or DPH. Butoxamine, a selective β-adrenergic receptor antagonist, reversed SALB influence on the activity of PB. SALB given alone or in combination with the tested AEDs did not affect animals' motor performance and memory after both single and 7 days administration.
Presented results show that SALB may decrease the antiepileptic efficacy of PB. A special caution is advised to patients with epilepsy receiving β-adrenergic receptors agonists in the pharmacotherapy of pulmonary and obstetrical disorders.
β-肾上腺素受体激动剂被广泛用于治疗哮喘或早产。由于癫痫患者的哮喘患病率较高,去甲肾上腺素能系统活动的调节可能会改变癫痫的病程,因此本研究的目的是研究最常用的β-肾上腺素受体激动剂之一沙丁胺醇(SALB)对四种经典抗癫痫药物(AEDs):丙戊酸钠(VPA)、卡马西平(CBZ)、苯妥英(DPH)和苯巴比妥(PB)在最大电休克(MES)诱导的癫痫发作中的抗惊厥作用的影响。
通过耳夹电极传递电流引起癫痫发作。还评估了 AED 和 SALB 对动物运动协调和记忆过程的影响。
单次 SALB 注射不会改变,但 7 天 SALB 给药会降低 MES 诱导的小鼠癫痫发作的惊厥阈。此外,SALB 在第 1 天和第 7 天腹腔注射会降低 MES 诱导的小鼠中 PB 的抗癫痫活性,但不会改变其他分析的 AEDs 的作用:VPA、CBZ 或 DPH。但是,β-肾上腺素受体选择性拮抗剂丁氧胺逆转了 SALB 对 PB 活性的影响。SALB 单独或与测试的 AED 联合使用,无论是单次还是连续 7 天给药,均不会影响动物的运动表现和记忆。
目前的结果表明,SALB 可能会降低 PB 的抗癫痫疗效。在治疗肺部和产科疾病的药物治疗中,建议接受β-肾上腺素受体激动剂的癫痫患者特别注意。