RESUMEN
Poisoning with pesticides containing convulsive substances is the cause of death of thousand people in the world. Convulsive syndrome can also develop with infection of the central nervous system, intracranial hemorrhages and strokes, alcohol withdrawal syndrome, eclampsia. Up to 10% of all of the people on the Earth had experienced seizures. The most common cause of seizures is epilepsy. Existing drugs are not always effective and have side effects. Alternative therapies are being developed. Valproates (derivatives of valproic acid) are one of the most studied drugs of choice for epilepsy and other variants of convulsive syndrome, have many years of experience in use, are included in international and Russian clinical guidelines for the treatment of epilepsy. The antiepileptic, mood stabilizing and neuroprotective properties of valproate due to pre- and postsynaptic modulation of GABA-ergic transmission, regulation of glutamate activity, serotonin and dopamine levels in the hippocampus, modulation of sodium, calcium and potassium channels, epigenetic effects on the body are described. However, valproates have a number of undesirable side effects, usually associated with high doses of drugs used for a long time. Attempts to reduce the risk through the development of drugs with controlled release of the active substance are not always effective - the high individual sensitivity of about 15% of patients with epilepsy makes standard doses toxic, the pharmacokinetics and effectiveness of the developed generics are significantly inferior to the original imported drug. An alternative could be the development of Russian preparations containing a proactive component from which valproic acid is gradually released during the metabolism.
Asunto(s)
Alcoholismo , Epilepsia , Síndrome de Abstinencia a Sustancias , Alcoholismo/tratamiento farmacológico , Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Humanos , Convulsiones/tratamiento farmacológico , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Ácido Valproico/uso terapéuticoRESUMEN
Expression of genes encoding the individual subunits of ionotropic GABAA receptor was assessed after acute and chronic intoxication of rats with ethanol. The chronic 1-month-long exposure to ethanol signifi cantly decreased (by 38%) expression of Gabrb1 gene in the hippocampus. Acute exposure to ethanol elevated expression of genes Gabrb1 (by 1.7 times), Gabra1 (by 3.8 times), and Gabra4 (by 6.5 times), although it diminished expression of Gabra2 gene by 1.4 times. In preliminarily alcoholized rats, acute intoxication with ethanol enhanced expression of genes Gabrb1 and Gabra5 by 1.7 and 8.7 times, respectively. There was neither acute nor chronic effect of ethanol on expression of gene Gabra3.