The effect of 1-(4-metoxyphenyl)-5-{2-[4-(4-metoxyphenyl) piperazine-1-yl]-2-oxoethyl}-1,5-dihydro-4Hpyrazole[ 3,4-D] pyrydine-4-one and sodium valproate on the level of inhibitory and excitatory neurotransmitters in the brain in the hemispheric asymmetry
DOI:
https://doi.org/10.24959/cphj.17.1412Keywords:
[3, 4-D]pyrydine-4-one derivatives, anticonvulsants, hemispherical asymmetry, inhibitory and excitatory neurotransmittersAbstract
Epilepsy affects about 1 % of the world population. Recently, epileptology considers the cerebral hemispheres (CH) as separate components, which differ due to the neurochemical hemisphere asymmetry.
Aim. To study the level of neurotransmitters and their correlation in the CH of mice receiving 1-(4-metoxyphenyl)-5-{2-[4-(4-metoxyphenyl) piperazine-1-yl]-2-oxoethyl}-1,5-dihydro-4H-pyrazole[3,4-D]pyrydine-4-one (compound
78553) and sodium valproate in intact animals, and the pentylenetetrazol kindling model.
Materials and methods. The brains of 44 mice used were divided into separate hemispheres and frozen. The levels of serotonin, GABA, glutamate, aspartate were determined by high voltage electrophoresis, and glycine – by thin-layer
chromatography. Compound 78553 was administered in the dose of 200 mg/kg, valproate sodium – 300 mg/kg.
Results. The hemispheric asymmetry of the level of neuroactive amino acids is absent in intact mice, and the serotonin level is higher in the left hemisphere (LH). Compound 78553 increases the levels of glycine, aspartate, serotonin without affecting GABA and glutamate. Sodium valproate elevates the GABA level and lowers the levels of other mediators. PTZ kindling causes a marked imbalance of neurotransmitters in the CH, increases the levels of excitatory neurotransmitters, reduces the inhibitory amino acids and depletes serotonin in the LH and the right hemisphere (RH). Compound 78553 in PTZ kindling increases the levels of GABA and glycine in the CH, restores their physiological level, raises the serotonin level and reduces the amount of excitatory amino acids up to the intact group level without the balance restoration between the hemispheres. Sodium valproate increases the level of GABA more efficiently than compound 78553, but has a weaker effect on glycine, restores the normal level of glutamate, slightly reducing the aspartate level. A moderate recovery effect is observed for serotonin in the RH, while in the LH it is almost absent. The hemispheric symmetry is recovered for glycine and aspartate.
Conclusions. Correlation analysis indicates that there is the conjugation deviation of the neurotransmitter exchange for acids and serotonin between the brain hemispheres in the PTZ kindling model. The changes in direction and the
strength of relationships between the neurotransmitter levels indicate the differences between biochemical mechanisms of the anticonvulsant action of compound 78553 and sodium valproate. The strong effect of sodium valproate
on GABA and glutamate in epilepsy can cause its high efficiency. A stronger effect on the metabolism of serotonin and glycine can partially explain the antiepileptic effect of compound 78553.
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