FURTHER-STUDIES ON ANTI-CONVULSANT AND PROCONVULSANT EFFECTS OF INHIBITORS OF NITRIC-OXIDE SYNTHASE IN RODENTS

We confirmed that the effects of inhibitors of nitric oxide (NO) synth ase, such as N-omega-nitro-L-arginine methyl ester and N-G-nitro-L-arg inine, differ depending on several experimental factors. Both compound s but not their less active enantiomers delayed picrotoxin-induced clo nus in mice yet increased the incidence of clonus following low-dose p icrotoxin. N-omega-nitro-L-arginine methyl ester significantly reduced the latencies of both myoclonus and clonus in older but not younger S prague-Dawley rats receiving pentylenetetrazol s.c. By contrast, there was no significant change in the latencies for myoclonus and clonus i n Wistar rats (older and younger). However, when pentylenetetrazol was administered i.p. rather than s.c., N-omega-nitro-L-arginine methyl e ster dramatically increased latencies of convulsive indicators, includ ing tonus, in both Sprague-Dawley and Wistar rats. N-omega-nitro-L-arg inine methyl ester also delayed tonus but not myoclonus or clonus in m ice, regardless of the systemic route of administration of pentylenete trazol. Both N-omega-nitro-L-arginine methyl eater and N-G-nitro-L-arg inine increased the tonic CD50 of pentylenetetrazol in mice and N-omeg a-nitro-L-arginine methyl eater delayed 4-aminopyridine-induced tonus. However, N-omega-nitro-L-arginine methyl ester reduced the tonic CD50 of both picrotoxin and 4-aminopyridine in mice and failed to suppress tonus following maximal electroshock. Evidently, inhibitors of NO syn thase are not universally effective antitonic drugs. (C) 1998 Elsevier Science B.V.