Baf M H, Subhash M N, Lakshmana K M, Rao B S
Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore, India.
Neurochem Int. 1994 Jan;24(1):67-72. doi: 10.1016/0197-0186(94)90130-9.
Sodium valproate is a well established anticonvulsant drug but its exact mode of action is not yet clear. With a view to find out whether the mechanism of action of sodium valproate is mediated by alteration in monoamine levels, apart from GABA, in brain, sodium valproate (200 mg/kg body wt) was administered i.p. to male adult Wistar rats for 45 days. The levels of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) were assayed in different brain regions using high performance liquid chromatographic (HPLC) method. It was noted that at the end of the experimental period there was no change in body or brain weight nor were there any neurological deficits as a result of sodium valproate administration. However, after administration of sodium valproate there was a significant increase in norepinephrine levels in hippocampus (P < 0.01) and brainstem (P < 0.01) while a significant decrease was noted in hypothalamus (P < 0.001). Dopamine levels were significantly increased in motor cortex (P < 0.01), hippocampus (P < 0.01) and hypothalamus (P < 0.001). Serotonin levels were significantly increased in striatum-accumbens and brain stem (P < 0.001). However a marginal increase was also observed in motor cortex and hippocampus. 5-HT levels were significantly decreased in hypothalamus (P < 0.001) and cerebellum (P < 0.01). The present findings suggest the possibility that the anticonvulsant effect of sodium valproate could be due to alterations in monoamine levels apart from its action on GABA, which would indicate also the efficacy of this drug in different types of seizures.
丙戊酸钠是一种公认的抗惊厥药物，但其确切作用机制尚不清楚。为了弄清楚丙戊酸钠的作用机制是否除了通过改变大脑中的γ-氨基丁酸（GABA）水平外，还通过改变单胺水平来介导，将丙戊酸钠（200毫克/千克体重）腹腔注射给成年雄性Wistar大鼠，持续45天。使用高效液相色谱（HPLC）法测定不同脑区中去甲肾上腺素（NE）、多巴胺（DA）和5-羟色胺（5-HT）的水平。结果发现，在实验期结束时，丙戊酸钠给药并未导致体重或脑重发生变化，也未出现任何神经功能缺损。然而，给予丙戊酸钠后，海马体（P < 0.01）和脑干（P < 0.01）中的去甲肾上腺素水平显著升高，而下丘脑（P < 0.001）中的去甲肾上腺素水平则显著降低。运动皮层（P < 0.01）、海马体（P < 0.01）和下丘脑（P < 0.001）中的多巴胺水平显著升高。伏隔核和脑干中的5-羟色胺水平显著升高（P < 0.001）。然而，在运动皮层和海马体中也观察到了轻微升高。下丘脑（P < 0.001）和小脑（P < 0.01）中的5-羟色胺水平显著降低。目前的研究结果表明，丙戊酸钠的抗惊厥作用可能是由于除了其对GABA的作用外，单胺水平的改变，这也表明该药物对不同类型癫痫发作的疗效。
