|Budget Amount *help
¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1990 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1989 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Nitrous oxide has a potent anticonvulsant action, but there are severa conflicting reports and the mechanism of anticonvulsant effect of nitrous oxide remains unknown.
The purpose of this research is to investigate further the pharmacology of anticonvulsant action of nitrous oxide using various experimental models of induced convulsions. The following convulsion models were employed : 1) the maximum electroshock (MES) 2) drug induced convulsion : a) Iidocaine (local anesthetics), b) pentylenetetrazol and bicuculine (GABA antagonist), and c) 4-aminopyridine (potassium channel blocker).
In the rat MES convulsion, severity of seizure was assessed by two indices : duration of tonic forelimb extention (TEF ; in sec), and motor seizure pattern (score). The control value for TFE was 11.9<plus-minus>1.1 (MEAN<plus-minus>SD) sec, and nitrous oxide suppressed it doseーdependently to 8.7<plus-minus>0.9sec, 6.3<plus-minus>0.9sec, 5.8<plus-minus>0.5sec, for 30%, 50% and 70% nitrous oxide, respectively
. The effect of 70% nitrous oxide on the MES convulsion was approximately equivalent to a dose of diazepam of 5mg/Kg i. p., and both drugs acts synerg
For drug induced convulsion, the change of the mean convulsion threshold dose of Iidocaine, pentyrentetrazol, bicuculine and 4-aminopyridine in air, by 70% nitrous oxide was examined. Nitrous oxide significantly increased the mean convulsion threshold dose of lidocaine, pentylenetetrazol, and bicuculine, but no anticonvulsant effect of nitrous oxide was seen on 4-aminopyridine convulsion. However, 4-aminopyridine convulsion was attenuated with diazepam (5mg/Kg i. p)
Although we and others have reported on the acute tolerance of nitrous oxide up to now, in the present study, with MES and nitrous oxide administration up to 120 min, acute tolerance was not found.
This study suggests that activation of brain inhibitory systems is the base for the anticonvulsant action of nitrous oxide. However it remains to be defined whether this is a direct (e. q. GABA receptor-channel) action of nitrous oxide, or not. The role of brain monoamines in the anticonvulsant ac ion of nitrous oxide should also be investigated. Less