Publications of Faculty of Medicine:Effect of clonidine in generalized seizures and its interaction with phenobarbitone sodium: Abstract

Title:
Effect of clonidine in generalized seizures and its interaction with phenobarbitone sodium
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Abstract:

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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