Experimental study of the influence of phenozanic acid and its combination with valproic acid on the development of the epileptic system

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OBJECTIVE

To study the effect of phenosanic acid (PA) and its combination with valproic acid (VA) on the development of the Epi system.

MATERIAL AND METHODS

A model of focal chronic epilepsy in rats was created by applying metallic cobalt to the surface of the sensorimotor area of the cortex. Long-term electrodes were implanted in the sensorimotor cortex of the left and right hemispheres, the hippocampus, and the hypothalamus. The effect of PA (80 mg/kg) and its combination with VA (200 mg/kg) on discharge activity was carried out on the 2nd day and at the stage of generalization of the Epi system — on the 6th day. The stability of the Epi system on day 10 was assessed by provoking the development of epileptic status (Epi status) in response to the administration of thiolactone homocysteine (HMC) at a dose of 5.5 mmol/kg.

RESULTS

In rats treated with PA, low discharge activity is observed, which is confirmed by the absence of EEG and motor manifestations of status epilepticus caused by HMC. PA does not suppress paroxysmal activity at the stages of development of the Epi system. VA significantly suppresses paroxysmal activity, but does not affect the formation of new foci of Epi activity in subcortical structures and the contralateral cortex. The epi system of rats treated with VA is characterized by high discharge activity by the 10th day of the experiment and lability to provocation of epi status. The combination of drugs is more pronounced than PA, but less than VA, reduces the numerical characteristics of paroxysmal activity in the brain structures of rats.

CONCLUSION

PA when administered alone, in combination with VA, causes a slowdown in the generalization of convulsive foci of Epi activity and prevents the formation of a stable Epi system. VA, having a pronounced anticonvulsant effect, does not weaken the development of the Epi system in the model of focal cobalt-induced epilepsy.

Keywords:

phenosanic acid

Dibufelon

convulsions

valproic acid

epilepsy

epileptic system

Authors:

Yakovleva A.A.

Zakusov Institute of Pharmacology

ORCID: 0009-0006-9108-2516

Litvinova S.A.

Zakusov Institute of Pharmacology

ORCID: 0000-0001-9139-2334

Gladysheva N.A.

Zakusov Institute of Pharmacology

ORCID: 0009-0001-4585-7142

Radontseva V.V.

Zakusov Institute of Pharmacology

ORCID: 0009-0008-9398-0824

Voronina T.A.

Zakusov Research Pharmacology Institute

SPIN RSCI: 5766-3452
Scopus AuthorID: 7103337584
ResearcherID: A-5990-2017
ORCID: 0000-0001-7065-469X

Received:

06.02.2024

Accepted:

07.02.2024

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