Semiokhina Af

Increase of brain endogenous monoamine oxidase inhibitory activity (tribulin) in experimental audiogenic seizures in rats: Evidence for a monoamine oxidase A inhibiting component of tribulin

Brain tribulin activity in rats with an inherited predisposition to audiogenic epilepsy was studied after seizures of different intensity were induced by an electric bell. Weak seizures (from 0 to 2 arbitrary units) did not produce any changes in endogenous inhibitory activity towards either monoamine oxidase (MAO) A or B. Moderate seizures were characterized by increases in both MAO A and MAO B inhibitory activity (up to 1.9-fold). Complete tonic epileptiform seizures with total areflexia (4 arbitrary units) induced further augmentation (up to 2.5-fold) of MAO A but not of MAO B inhibitory activity. This dissociation between the two inhibitory activities points to the existence of a separate MAO A-inhibiting component of brain tribulin which is different from isatin.

Efficacy of Pirlindole, a Highly Selective Reversible Inhibitor of Monoamine Oxidase Type A, in the Prevention of Experimentally Induced Epileptic Seizures

SummaryIntraperitoneal administration of pirlindole (pirazidole) or ‘soluble pirlindole’ 50 mg/kg body-weight prolonged the onset of seizures and decreased the intensity of seizures in rats genetically selected for high sensitivity to audiogenic hereditary epilepsy [Krushinsky-Molodkina (KM) rats]. In this experimental model of epilepsy, pirlindole prevented qualitative alteration (transformation) in the catalytic activity of membrane-bound type A monoamine oxidases (MAO-A), pathogenetically important for the development of the audiogenic seizures. Modification of the enzymatic properties of the monoamine oxidases causes an increase in γ-aminobutyric acid (GABA) deamination in the mitochondrial fraction of the brain. The data obtained suggest that selective inhibitors of MAO-A, such as pirlindole, may prevent experimental epileptic seizures.

The role of lipid peroxidation in the possible involvement of membrane-bound monoamine oxidases in gamma-aminobutyric acid and glucosamine deamination in rat brain. Focus on chemical pathogenesis of experimental audiogenic epilepsy.

Incubation of rat brain synaptosomes and mitochondria with LPO inducers (Fe2+ and ascorbate) was accompanied by a decrease of deamination of serotonin (substrate of MAO-A) in mitochondria, but not in synaptosomes, with simultaneous stimulation of GABA and GLCA deamination, apparently owing to modification of catalytic properties of brain membrane-bound MAO. Oxidation of PEA (substrate of MAO-B) was insignificantly altered in both fractions. Reactions of deamination of serotonin, GABA, and GLCA (but not PEA), were highly sensitive to a selective inhibitor of MAO-A pyrazidol (pyrlindole). Isoniazid and hydrazides of quinoline carbonic acids (inhibitors of both modified MAO and copper-containing amine oxidases) strongly inhibited deamination of GABA and GLCA. During epileptiformic seizures in rats, genetically selected for high incidence of audiogenic epilepsia, stimulation in brain synaptosomes and mitochondria of LPO was observed. This was accompanied by a marked decrease in serotonin and PEA deamination, with a simultaneous increase in GABA and GLCA deamination in both fractions. The data obtained suggest that appearance of GABA-deaminating activity owing to modification of catalytic properties of MAO, might be an essential pathogenetic component in the development of epileptic seizures.