ABSTRACT
Experiments were carried out with smooth muscles preparations of 24 rats (gastric corpus) and 36 guinea pigs (gastric corpus and taenia coli). Their contractile responses were recorded isometrically using tensile transducers. The bioelectric activity was determined by the single sucrose-gap method. Depending on the concentration sodium valproate elicits two types of responses from the smooth muscle of gastrointestinal tract of rats and guinea pigs: a contractile response, at concentrations less than 10(-4) g/ml, and a relaxant response, at concentrations higher than 10(-4) g/ml. At concentrations below 10(-4) g/ml sodium valproate induces contractions of the smooth muscle taken from the rat and guinea pig gastrointestinal tract. These contractions can be abolished by indomethacin. It may be concluded, therefore, that the contractile effect of sodium valproate has a prostaglandin basis. At concentrations higher than 10(-4) g/ml, sodium valproate hyperpolarizes the smooth muscle tissues, reduces the frequency and amplitude of the spontaneously generated spike potentials and relaxes the preparations. These effects are blocked by picrotoxin. Sodium valproate in high concentrations increases the endogenous level of the gamma-aminobutyric acid stimulating at the same time the prostaglandin synthesis which is inadequate to compensate the relaxant effect induced by elevated level of the endogenous gamma-aminobutyric acid.
Subject(s)
Anticonvulsants/pharmacology , Muscle Contraction/drug effects , Muscle, Smooth/physiology , Valproic Acid/pharmacology , Animals , Guinea Pigs , In Vitro Techniques , Muscle, Smooth/drug effects , RatsABSTRACT
A neuropharmacological study was performed to investigate the effect of valproate sodium (VS) used to suppress the barbiturate and phenytoin withdrawal syndrome induced experimentally in 1152 male Wistar rats. Valproate sodium was administered by mouth according to the following protocol: initial bolus dose of 400 mg/kg b.w. followed eight hours later by the first maintaining dose of 50 mg/kg b.w. This was given every 12 hours for five days. VS plasma levels were determined by gas chromatography. The therapeutic effect of valproate sodium was assessed by the seizure reactivity of the experimental and the control animals to an electroshock (50 mA/0.1 sec.). The results strongly indicate that valproate sodium inhibits the experimentally induced barbiturate and phenytoin withdrawal syndrome without causing drug dependance. It is suggested that some of the valproate sodium metabolites possess antiwithdrawal effect.
Subject(s)
Barbiturates/adverse effects , Phenytoin/adverse effects , Seizures/chemically induced , Substance Withdrawal Syndrome/drug therapy , Valproic Acid/therapeutic use , Animals , Male , Rats , Rats, Wistar , Substance Withdrawal Syndrome/etiologyABSTRACT
This epidemiological study reviewed the frequency of prescribing antiepileptic drugs for the period 1982 to 1991 in four regions of Bulgaria. The study included 8,340 outpatients with epilepsy. The therapeutic approaches to primary generalized, focal, and secondary types of epilepsy were evaluated. The drug of preference in all types of epilepsy was found to be phenobarbital (26.3 to 37.8%), followed by carbamazepine (14.0 to 29.8%), bellonal, sacerno, phenytoin, etc. Valproate was prescribed only in a few cases (0 to 2.1%). Combinations of phenobarbital anc carbamazepine prevailed in the therapeutic approach to epilepsy. The share of polytherapy in the treatment of epilepsy tended to decrease in favour of monotherapy. The data on the antiepileptic drug utilization given in the present study are calculated in the internationally accepted unit, a daily defined dose.
Subject(s)
Anticonvulsants/therapeutic use , Epilepsy/epidemiology , Adolescent , Adult , Aged , Anticonvulsants/administration & dosage , Bulgaria/epidemiology , Drug Prescriptions , Drug Therapy, Combination , Epilepsy/drug therapy , Female , Humans , Male , Middle AgedABSTRACT
The present study was undertaken to investigate some important processes of neurotransmission which occur in rat brains under the influence of valproate sodium. Valproate sodium is used for the suppression of the withdrawal effects resulting from sudden discontinuation of phenobarbital and phenytoin treatment. Corpus striatum, hippocampus and cortex were isolated operatively. The amounts of neuromediators (dopamine, noradrenaline, serotonin and gamma-aminobutyric acid) were determined using fluorometry. The results show that the anti-withdrawal effect of valproate sodium established in previous research probably is due to active metabolites which increase the amount of gamma-aminobutyric acid in all brain structures. In suppressing barbiturate and phenytoin withdrawal syndrome using valproate sodium, the previously established anti-withdrawal effect probably is due to high tissue levels of dopamine in hippocampus and to noradrenaline in the cortex, hippocampus and corpus striatum. This anti-withdrawal effect continues for three days after the discontinuation of valproate sodium. This probably is due to the accumulation of the inhibitory neuromediator GABA in the cortex, hippocampus and corpus striatum and to the elevated level of dopamine in hippocampus. The results raise new possibilities for developing medicinal substances, which possess anti-withdrawal action, from the metabolites of the valproate sodium.
