Mares P, Chino M, Kubová H, Mathern P, Veliký M
Institute of Physiology, Academy of Sciences of the Czech Republic, Vídenská 1083, CZ 142 20 4, Prague, Czech Republic.
Epilepsy Res. 2000 Dec;42(2-3):183-9. doi: 10.1016/s0920-1211(00)00179-0.
Developmental changes of transport of drugs into the brain play an important role in ontogenetic neuropharmacology. Two convulsant drugs with different mechanisms of action (glutamate and bicuculline methiodide) were chosen to demonstrate these changes in developing rats. High dose of glutamate (4 g/kg i.p.) induced both minimal (predominantly clonic) and generalized tonic-clonic seizures in rat pups 7, 12, and 18 days old. In contrast, seizures were only exceptionally observed in 25 and 90 days old animals. Bicuculline methiodide was administered in a dose of 2 or 20 mg/kg i.p. The first sign of bicuculline methiodide action in all age groups was represented by automatisms, a symptomatology never seen after bicuculline hydrochloride administration. Minimal seizures were induced in 12-day-old and in a few 18-day-old and adult rats. Generalized seizures were common after the higher dose of bicuculline methiodide in 7- and 12-day-old rat pups, seldom in 18-day-old ones and never seen in 25-day-old and adult animals. Both glutamate and bicuculline methiodide enter the brain in immature rats but the mechanisms are probably different - glutamate is transported actively through the blood-brain barrier whereas no similar system is known for bicuculline methiodide.
药物向脑内转运的发育变化在个体发生神经药理学中起着重要作用。选用两种作用机制不同的惊厥药物（谷氨酸和甲磺酸荷包牡丹碱）来证明发育中大鼠的这些变化。高剂量谷氨酸（4 g/kg腹腔注射）可在7日龄、12日龄和18日龄的幼鼠中诱发轻微（主要为阵挛性）和全身性强直-阵挛性惊厥。相比之下，在25日龄和90日龄的动物中仅偶尔观察到惊厥。甲磺酸荷包牡丹碱以2或20 mg/kg腹腔注射给药。在所有年龄组中，甲磺酸荷包牡丹碱作用的首个迹象均表现为自动症，这是盐酸荷包牡丹碱给药后从未见过的症状学表现。12日龄以及部分18日龄和成年大鼠中诱发了轻微惊厥。在7日龄和12日龄幼鼠中，较高剂量的甲磺酸荷包牡丹碱给药后全身性惊厥很常见，18日龄大鼠中少见，而在25日龄和成年动物中从未见过。谷氨酸和甲磺酸荷包牡丹碱均可进入未成熟大鼠的脑内，但机制可能不同——谷氨酸通过血脑屏障被主动转运，而甲磺酸荷包牡丹碱尚无类似的转运系统。
