Reading School of Pharmacy, University of Reading, Whiteknights, Reading, UK.
Br J Pharmacol. 2012 Dec;167(8):1629-42. doi: 10.1111/j.1476-5381.2012.02207.x.
Phytocannabinoids in Cannabis sativa have diverse pharmacological targets extending beyond cannabinoid receptors and several exert notable anticonvulsant effects. For the first time, we investigated the anticonvulsant profile of the phytocannabinoid cannabidivarin (CBDV) in vitro and in in vivo seizure models.
The effect of CBDV (1-100 μM) on epileptiform local field potentials (LFPs) induced in rat hippocampal brain slices by 4-aminopyridine (4-AP) application or Mg(2+) -free conditions was assessed by in vitro multi-electrode array recordings. Additionally, the anticonvulsant profile of CBDV (50-200 mg·kg(-1) ) in vivo was investigated in four rodent seizure models: maximal electroshock (mES) and audiogenic seizures in mice, and pentylenetetrazole (PTZ) and pilocarpine-induced seizures in rats. The effects of CBDV in combination with commonly used antiepileptic drugs on rat seizures were investigated. Finally, the motor side effect profile of CBDV was investigated using static beam and grip strength assays.
CBDV significantly attenuated status epilepticus-like epileptiform LFPs induced by 4-AP and Mg(2+) -free conditions. CBDV had significant anticonvulsant effects on the mES (≥100 mg·kg(-1) ), audiogenic (≥50 mg·kg(-1) ) and PTZ-induced seizures (≥100 mg·kg(-1) ). CBDV (200 mg·kg(-1) ) alone had no effect against pilocarpine-induced seizures, but significantly attenuated these seizures when administered with valproate or phenobarbital at this dose. CBDV had no effect on motor function.
These results indicate that CBDV is an effective anticonvulsant in a broad range of seizure models. Also it did not significantly affect normal motor function and, therefore, merits further investigation as a novel anti-epileptic in chronic epilepsy models.
This article is part of a themed section on Cannabinoids. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.167.issue-8.
大麻中的植物大麻素在延伸至大麻素受体以外的多种药理学靶标上具有不同的作用，并且几种植物大麻素具有显著的抗惊厥作用。我们首次在体外和体内癫痫发作模型中研究了植物大麻素大麻二酚（CBDV）的抗惊厥作用。
通过在体多电极阵列记录，评估 CBDV（1-100 μM）对 4-氨基吡啶（4-AP）应用或镁缺乏条件下诱导的大鼠海马脑片癫痫样局部场电位（LFPs）的影响。此外，还在 4 种啮齿动物癫痫发作模型中研究了 CBDV（50-200 mg·kg(-1) ）的体内抗惊厥作用：最大电休克（mES）和听觉性癫痫发作，以及戊四氮（PTZ）和匹鲁卡品诱导的癫痫发作。还研究了 CBDV 与常用抗癫痫药物联合使用对大鼠癫痫发作的影响。最后，通过静态束和握力试验研究了 CBDV 的运动副作用特征。
CBDV 显著减弱了由 4-AP 和镁缺乏条件诱导的癫痫样 LFPs。CBDV 对 mES（≥100 mg·kg(-1) ）、听觉性（≥50 mg·kg(-1) ）和 PTZ 诱导的癫痫发作（≥100 mg·kg(-1) ）具有显著的抗惊厥作用。CBDV（200 mg·kg(-1) ）单独使用对匹鲁卡品诱导的癫痫发作没有作用，但在该剂量下与丙戊酸钠或苯巴比妥联合使用时，可显著减弱这些癫痫发作。CBDV 对运动功能没有影响。
这些结果表明，CBDV 是一种广泛的癫痫发作模型中的有效抗惊厥药。此外，它对正常运动功能没有显著影响，因此值得进一步研究，作为慢性癫痫模型中的新型抗癫痫药。
本文是关于大麻素的专题部分的一部分。要查看此部分中的其他文章，请访问 http://dx.doi.org/10.1111/bph.2012.167.issue-8.
