Gautam S K, Kulkarni S K
Department of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Indian J Exp Biol. 1991 Jul;29(7):636-40.
Digoxin (7.5 micrograms icv) induced 'pop-corn' type of convulsions and 100% mortality. The GABA-ergic agents produced varying degree of protection against digoxin-induced neurotoxicity. Diazepam (4 mg/kg) offered significant protection whereas pentobarbital (5 mg/kg) and baclofen (5 mg/kg) markedly reduced per cent mortality, but ethanol (2 g/kg), progabide (50 mg/kg) and muscimol (0.5 mg/kg) as well as GABA (50 mg/kg) could not offer significant protection in doses used. GABA-ergic agonists; GABA, baclofen, diazepam and pentobarbital when administered along with MK-801 (0.5 mg/kg) a non-competitive NMDA antagonist, a potentiation of anticonvulsant action of MK-801 was observed. MK-801 showed potent anticonvulsant profile in dose range (0.25-1 mg/kg) studied. A synergistic influence of Mg2+ and K+ ions on NMDA receptor antagonism was also observed. A role of GABA-ergic facilitation and NMDA antagonism as a potential anticonvulsant approach in digoxin-induced convulsions in rats has been suggested.
地高辛（脑室内注射7.5微克）可诱发“爆米花”样惊厥并导致100%的死亡率。γ-氨基丁酸能药物对由地高辛引起的神经毒性有不同程度的保护作用。地西泮（4毫克/千克）提供了显著的保护作用，而戊巴比妥（5毫克/千克）和巴氯芬（5毫克/千克）显著降低了死亡率，但乙醇（2克/千克）、普罗加比（50毫克/千克）、蝇蕈醇（0.5毫克/千克）以及γ-氨基丁酸（50毫克/千克）在所使用的剂量下未能提供显著保护。γ-氨基丁酸能激动剂；γ-氨基丁酸、巴氯芬、地西泮和戊巴比妥与非竞争性N-甲基-D-天冬氨酸（NMDA）拮抗剂MK-801（0.5毫克/千克）一起给药时，观察到MK-801的抗惊厥作用增强。在所研究的剂量范围（0.25 - 1毫克/千克）内，MK-801显示出强大的抗惊厥作用。还观察到镁离子和钾离子对NMDA受体拮抗作用的协同影响。有人提出γ-氨基丁酸能促进作用和NMDA拮抗作用作为一种潜在的抗惊厥方法在大鼠地高辛诱发惊厥中的作用。
