EFFECTS OF CLONAZEPAM ON LEPTAZOL AND STRYCHNINE-INDUCED SEIZURES IN MICE AND CHICKS 

EFFECTS OF CLONAZEPAM ON LEPTAZOL AND STRYCHNINE-INDUCED SEIZURES IN MICE AND CHICKS 

Abstract:

The effects of clonazepam, Levodopa, 3, 4-d ihydroxyphenylserine (DOPS), 5-HTP on seizures elicited by strychnine and Leptazol were investigated in chicks and mice. The effect of leptazol and clonazepam on chick EEG and EMG were also studied. 2. Clonazepam (0.02 – 0.03 mg kg-1) protected mice Lnst PTZ convulsions and mortality while higher doses (0.05 – 0.1 mg kg-1) offered complete protection against PTZ (90 mg kg-1) convulsions and mortality. CNP (0.02 mg kg”1) significantly (p<0.0025) delayed the onset of tonic seizure induced by PTZ. It significantly (p<0.05) reduced the proportion of mice that experienced tonic convulsions and mortality in a population of mice after PTZ (90 mg kg-1). 3. Clonazepam (0.02 – 0.1 mg kg-1) protected chicks against PTZ and strychnine-induced convulsions and mortality. CNP (0.02 mg kg-1) significantly (p<0.005) protected chicks against PTZ (80 mg kg-1) induced convulsions and mortality, while CNP (0.05 mg kg-1) significantly (p<0.0005) protected chicks against strychnine induced convulsions. It significantly (p<0.05 and p<0.0l) reduced the proportion of chicks that experienced tonic convulsions and mortality in a population after PTZ (80 mg kg -1) and strychnine (0.1 mg kg-1) respectively. 4. DOPS (1-6 mg kg-1) significantly (p<0.05) potentiated PTZ (80 mg kg-1) induced convulsions and mortality in mice. CNP (0.02 mg kg-1) protected mice against DOPS potentiated PTZ convulsions and mortality. 5. Reserpine (2.5 mg kg-1) and d-amphetamine (2.5 – 4.0 mg kg-1) significantly (p<0.05) increase the incidence of tonic convulsions and mortality rate of PTZ induced convulsions in both mice and chicks. CNP (0.02 mg kg-1) significantly (p< 0.05) protected mice against reserpine and d-amphetamine increased PTZ convulsions and mortality. 6. 5-HTP (100 – 120 mg kg-1) significantly (p< 0.005) reduced the incidence of tonic convulsion induced by PTZ (90 mg kg-1) in mice. 5-HTP also potentiated the anticonvulsant effect of clonazepam (0.02 mg kg- 1). 7. P-CPA (300 mg kg-1) and Methysergide (H mg kg-1) increased the incidence of tonic convulsion induced by PTZ (80 mg kg-1) in mice. CNP (0.02 mg kg-1) antagonised the influence of p-CPA and methysergide on PTZ-induced convulsions. 8. L-dopa (30 and 40 mg kg-1) significantly (p< 0.025) protected mice against PTZ (90 mg kg-1) induced convulsions. Lower doses (12.5 and 20 mg kg-1) of L-dopa protected mice against PTZ convulsions. L-dopa also potentiated the anticonvulsant effect of CNP on PTZ convulsions. 9. Pimozide (1-2.5 mg kg-1) significantly (p<0,025) potentiated PTZ (85 and 90 mg kg-1) induced convulsions and mortality. The protective effect of CNP (0.02 mg kg-1) against PTZ-induced convulsions and mortality was antagonised by pimozide. In addition, pimozide (2.5 mg kg-1) antagonised the anticonvulsant effect of dopamine (40 mg kg- 1). 10. Sulpiride (40 and 50 mg kg-1) significantly (p<0.05) protected mice against PTZ-induced convulsions and mortality. In addition, sulpiride (40 mg kg-1) potentiated the anticonvulsant effect of CNP (0.02 mg kg- 1). 11. INH (25 – 200 mg kg-1) significantly (p 0.05) potentiated PTZ convulsions and mortality. At high doses (100 and 200 mg kg-1) the incidence of tonic convulsions and mortality were 100%, while the lower doses (25 and 50 mg kg-1) caused a significant (p<0.05) increase in the incidence of tonic convulsion and mortality rate. INH (200 mg kg-1) alone without PTZ induced a 50% incidence of tonic convulsion and 25% mortality rate 2 hours after injection. 12. R015-1788 (20 mg and I4.0 mg kg-1) significantly (p<0.05) antagonised the anticonvulsant effect of CNP (0.02 mg kg-1) on PTZ convulsions and mortality in mice, while R015-1788 (5.0 – 15 mg kg-1) did not produce significant increase in the incidence of tonic convulsion induced by PTZ in the presence of CNP. (ix) 13. PTZ (80 mg kg-1) desynchronized the EEG of the hyperstriatum, optic tectum, the pontine reticular formation and increased the amplitude of the EMG with characteristic spikes in 5 day old chick, while clonazepam (0.02 mg kg-1) synchronized the EEG of the hyperstriatum and the pontine reticular formation. In addition, the amplitude of the EMG was reduced while the frequency was increased, 14. Clonazepam (0.02 mg kg-1) delayed the appearance of the characteristic EEG spikes and abolished the full body convulsion produced by PTZ. Clonazepam also abolished the increased EMG activity produced by leptazol alone.

EFFECTS OF CLONAZEPAM ON LEPTAZOL AND STRYCHNINE-INDUCED SEIZURES IN MICE AND CHICKS