Influence of aminophylline and strychnine on the protective activity of excitatory amino acid antagonists against maximal electroshock-induced convulsions in mice

Abstract

Aminophylline reversed the protective action of both, D-3-(2-carboxypiperazine-4-yl)-1-propenyl-1-phosphonic acid (D-CPP-ene-a competitive NMDA antagonist) and valproate (used as a conventional antiepileptic drug for comparative purposes) against maximal electroshock-induced seizures. The respective ED50 values of aminophylline were 55.7 and 98.4 mg/kg i.p. However, aminophylline (up to 100 mg/kg i.p.) did not influence the protective efficacy of 1-(4-aminophenyl)-4-methyl-7,8-methyl- enedioxy-5H-2,3-benzodiazepine (GYKI 52466-a non-NMDA antagonist). Strychnine affected the protection provided by D-CPP-ene, GYKI 52466, and valproate against maximal electroshock-the ED50 values of strychnine for the reversal of the anticonvulsive effects of D-CPP-ene, GYKI 52466 or valproate were 0.082, 0.35 and 0.28 mg/kg s.c., respectively. An involvement of strychnine sensitive glycinergic receptor-mediated events in the mechanism of the anticonvulsive activity of excitatory amino acid antagonists and valproate may be postulated. The ineffectiveness of aminophylline to reduce the anticonvulsive effects of GYKI 52466 may distinguish a new class of antiepileptic drugs offering an advantage over conventional antiepileptics in patients with epilepsy, requiring aminophylline for pulmonary reasons.

Gas therapy strategies for depression and schizophrenia: A review

“…Molsidomine has been shown to have anticonvulsant effects in rats [47] and to potentiate the anticonvulsant effects of riluzole and valproic acid (two independent NMDA antagonists) in mice. [48] In many animal models, molsidomine works well against memory deficits, suggesting that it can improve cognitive impairment. [49,50] Both patients with depression and schizophrenia are likely to have cognitive impairment including memory impairment, so this suggests that molsidomine holds promise for treating both depression and schizophrenia.…”

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“…At higher doses inhibition of phosphodiesterase activity including mobilization of intracellular calcium ions from labile stores are said to be implicated in aminophylline-induced seizures. 29 However, a report by Ray et al, 30 has implicated oxidative stress due to the generation of free radicals and reactive oxygen species to be responsible for the seizures induced by aminophylline. This suggest that plant extract with antioxidant activity are able to prevent convulsion induced by aminophylline which is likely to be the mechanism of action of this extract as S. officinarum has been reported to possess antioxidant activity.…”