The role of nitric oxide in the proconvulsant effect of delta-opioid agonist SNC80 in mice

The involvement of nitric oxide (NO) in modulation of seizure susceptibility by delta-opioid agonist (+)-4-((alpha R)-alpha-((2S, 5R)-4-allyl-2, 5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N, N-diethyl-benzamide (SNC80) was examined in mice. Systemic administration of SNC80 (0.1-5 mg/kg, intraperitoneally (i.p.)) decreased the threshold for clonic seizures induced by pentylenetetrazole. The non-specific NO synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (3-20 mg/kg, i.p.), but not the specific inducible NOS inhibitor, aminoguanidine (50 and 100 mg/kg, i.p.) inhibited the proconvulsant effect of SNC80. On the other hand, NO substrate, L-arginine (30 and 60 mg/kg, i.p.) potentiated the proconvulsant effect of a lower dose of SNC80 (0.5 mg/kg). These results support the involvement of NO, produced by constitutive NOS, in the proconvulsant effect of the delta-opioid agonist.