After 60 years,
lithium is still the mainstay in the treatment of
mood disorders and widely used in clinic. In addition to its mood stabilizer effects,
lithium also shows some
anticonvulsant properties. Similar to
lithium,
agmatine also plays a protective role in the CNS against
seizures and has been reported to enhance the effect of different
antiepileptic agents. Moreover, both
agmatine and
lithium have modulatory effects on α(2)-adrenoceptors. So, we designed this study: 1) to investigate whether
agmatine and
lithium show an additive effect against
clonic seizures induced by
pentylenetetrazole; 2) to assess whether this additive effect is mediated through the α(2)-
adrenoceptor or not. In our study, acute administration of a single effective dose of
lithium chloride (30 mg/kg, i.p.) increased the seizure threshold. Pre-treatment with low and, per se, non-effective doses of
agmatine (1 and 3mg/kg) potentiated a sub-effective dose of
lithium (10mg/kg). Interestingly, the
anticonvulsant effects of these effective combinations of
lithium and
agmatine were prevented by pre-treatment with low and non-effective doses of
yohimbine [α(2)-
adrenoceptor antagonist] (0.1 and 0.5mg/kg). On the other hand,
clonidine [α(2)-
adrenoceptor agonist] augmented the
anticonvulsant effect of a sub-effective combination of
lithium (5mg/kg i.p.) and
agmatine (1mg/kg) at relatively low doses (0.1 and 0.25mg/kg). In summary, our findings demonstrate that
agmatine and
lithium chloride exhibit additive
anticonvulsant properties which seem to be mediated through α(2)-
adrenoceptor.