The
anticonvulsant effects of
agmatine, an endogenous
polyamine and a metabolite of
l-arginine, have been shown in various experimental seizure models.
Agmatine also potentiates the anti-seizure activity of
morphine. The present study aimed to investigate a possible involvement of
nitric oxide (NO) pathway in the protection by
agmatine and
morphine co-administration against
pentylenetetrazole (PTZ) -induced seizure in male mice. To this end, the thresholds for the
clonic seizures induced by the
intravenous administration of PTZ, a
GABA antagonist, were assessed. Intraperitoneal administration of
morphine at lower dose (1mg/kg) increased the seizure threshold. Also intraperitoneal administration of
agmatine (5 and 10mg/kg) increased the seizure threshold significantly. Combination of subeffective doses of
morphine and
agmatine led to potent
anticonvulsant effects. Non-effective doses of
morphine (0.1 and 0.5mg/kg) were able to induce
anticonvulsant effects in mice pretreated with
agmatine (3mg/kg). Concomitant administration of either the non-selective
nitric oxide synthase (NOS) inhibitor
L-NAME (1, 5mg/kg, i.p.) or the selective NOS inhibitor 7-NI (15, 30mg/kg, i.p.), with an ineffective combination of
morphine (0.1mg/kg) plus
agmatine (1mg/kg) produced significant
anticonvulsant impacts. Moreover, the NO precursor,
l-arginine (30, 60mg/kg, i.p.), inhibited the
anticonvulsant action of
agmatine (3mg/kg) plus
morphine (0.5mg/kg) co-administration. Our results indicate that pretreatment of animals with
agmatine enhances the
anticonvulsant effects of
morphine via a mechanism which may involve the NO pathway.