Clonidine has an imidazoline structure and is
known to stimulate central alpha 2 adrenergic
receptors. Clonidine and other alpha 2 agonists
have anti-convulsant action. The anticonvulsant
profile of clonidine and its co-administration
with phenobarbitone sodium was investigated in
mice. Yohimbine (alpha 2 blocker) and naloxone
(opiate antagonist) were used to show their
effects on the anti-convulsant action of
clonidine.Pentylene tetrazole(PTZ) was used to
induce more or less generalized convulsions in
mice. The effect of the given drugs on PTZ induced
convulsions regarding onset of convulsions,number
of convulsions and initial PTZ convulsive dose was
Investigated. Game amino butyric acid (GABA)
content in cerebral cortex and hind brain of
treated mice was estimated in a trial to display
the possible mechanism' through which clonidine
acts.
It was found that clonidine significantly
protected mice against PTZ induced convulsions. It
prolongs significantly time needed for the onset
of convulsions to 4.3s0.8 minuteScompared to 0.9
s 0.3 minute in control group and reduces
significantly number of convulsions to 6 S 1.1
compared to 25.1 s 2.6 in control mice. It also ,
increases significantly initial convulsive dose of
PTZ to 16.8 s 2.8 mg compared to 9.7 * 1.6 mg in
control group. GABA content showed a significant increase in cerebral cortex and hind brain of mice
pre-treated with clonidine which showed values 360
* 31.4 and 414.62 * 39.45 ug/g wet tissue compared
to control values 307 * 25.1 and 284 * 14.73 ug/g
wet tissue respectively.
Yohimbine antagonized the protective effect of
clonidine against PTZ induced convulsions. It
significantly reduces time needed for onset of
convulsions increases number of convulsions
,decreases initial PTZ convulsive dose and
decreases GABA content when given with clonidine
compared to mice given clonidine alone.On the
other hand, Naloxone increases significantly time
needed for onset of convulsions,reduces number of
convulsions,increases initial PTZ convulsive dose
and GABA content when used with clonidine compared
to mice given clonidine alone.
Our results also showed that phenobarbitone
potentiated the protective anti-convulsant effect
of clonidine. Phenobarbitone when used in
combination with clonidine induced -significant
increase in time needed for onset of
convulsions,initial convulsive PTZ dose & GABA
content and significant decrease in number of
convulsions when compared to mice given clonidine
or phenobarbitone alone.
These results suggest that clonidine has a
protective effect against PTZ induced convulsions
in mice . This protective effect of clonidine
against seizures is antagonized by yohimbine and
potentiated by phenobarbitone and naloxone. This
effect of clonidine may be due to increased GABA
level in cerebral cortex and hindbrain.
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