The synergistic anticonvulsant effect of agmatine and morphine: Possible role of alpha 2-adrenoceptors

Recent demonstrations of the anticonvulsant properties of agmatine suggest it may be considered as a potential adjunct for protection against seizure. We investigated the possibility of an additive anticonvulsant effect between low doses of agmatine and morphine. The thresholds for the clonic seizures induced by the intravenous administration of gamma-aminobutyric acid (GABA)-antagonist, pentylenetetrazole (PTZ) were assessed in mice. Morphine at lower doses (1-3 mg/kg) increased and at higher doses (30, 60 mg/kg) decreased the seizure threhsold. Pretreatment with a per se non-effective dose of agmatine (1 mg/kg) potentiated the anticonvulsant effect of morphine. The combination of subeffective doses of agmatine and morphine led to potent anticonvulsant effects. The proconvulsant effect of morphine was attenuated by agmatine. Yohimbine with a dose (1 mg/kg) incapable of affecting seizure threshold reversed the effect of agmatine on both anticonvulsant and proconvulsant effects of morphine. These results suggest that agmatine potentiates the anticonvulsant effect of morphine and alpha 2-adrenoceptors may be involved in this effect.