EFFECTS OF CLONAZEPAM ON LEPTAZOL AND STRYCHNINE-INDUCED SEIZURES IN MICE AND CHICKS BY'
EFFECTS OF CLONAZEPAM ON LEPTAZOL AND STRYCHNINE-INDUCED SEIZURES IN MICE AND CHICKS BY'
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Date
1988-03
Authors
JAMES, AUTA
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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.
Description
A THESIS SUBMITTED TO
AHMADU BELLO UNIVERSITY, ZARIA
IN PARTIAL FULFILLMENT FOR THE DEGREE OF
MASTER OF SCIENCE IN PHARMACOLOGY.
DEPARTMENT OF PHARMACOLOGY AND CLINICAL
PHARMACY, FACULTY OF PHARMACEUTICAL SCIENCES.
MARCH 1988.
Keywords
EFFECTS,, CLONAZEPAM,, LEPTAZOL,, STRYCHNINE,, INDUCED,, SEIZURES,, MICE,, CHICKS.