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Results for “Valproate”

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PubMed1992

The anxiogenic-like effects of pentylenetetrazole in mice treated chronically with carbamazepine or valproate.

The chronic effects of carbamazepine administration (5, 10, 20 mg/kg i.p. daily for 14 days) on the anxiogenic response to pentylenetetrazole were studied in the light/dark aversion test. In mice, these effects were compared with those of sodium valproate (100, 200 and 300 mg/kg i.p.), a putative anxiolytic drug, and lorazepam (0.025, 0.05 and 0.10 mg/kg i.p.), a well-established anxiolytic drug. The results showed that the anxiogenic-like behavior induced by subconvulsant doses of pentylenetetrazole (15 mg/kg i.p.) was antagonized by the chronic administration of lorazepam as well as sodium valproate, a GABA agonist. In fact, the increased aversion of mice for the light compartment of the light/dark box was reduced. Carbamazepine failed to significantly alter the anxiogenic-like behavior of mice. These findings provide further evidence for the absence of anxiolytic properties of carbamazepine and for a behavioral anxiolytic profile of valproate similar to that of benzodiazepines.

Animals↗

PubMedDate not supplied

Certain aspects of interaction between sodium valproate and other anticonvulsant drugs in the therapy of epilepsy in children.

The serum valproate (VPA) concentration and the clinical effects of polytherapy with other antiepileptic drugs: phenobarbital (PB), clonazepam (CZP), diazepam (DZ), clobazam (CLO), ethosuximide (ESX) were estimated. VPA serum levels were reduced when this drug was combined with phenobarbital. Clobazam given together with valproate led to an increase in the serum concentration of the former drug. VPA serum levels were without significant changes when the drug was combined with either ethosuximide or 1-4-benzodiazepines. The best therapeutical effects were found after polytherapy sodium valproate with ethosuximide and clobazam in primary generalized seizures.

Adolescent↗

PubMed2003

Intravenous sodium valproate in status epilepticus.

A study was conducted to observe the effect of intravenous sodium valproate in status epilepticus. Eleven patients with status epilepticus, who were resistant to conventional drugs, underwent treatment with intravenous sodium valproate. The seizures were controlled in 10 patients within 24-48 hrs of starting treatment. No complications were observed during therapy. We conclude that intravenous sodium valproate can be recommended for Myoclonic status epilepticus and non-convulsive status epileticus.

Adolescent↗

PubMed2004

Acute pancreatitis and diabetic ketoacidosis in non-diabetic person while on treatment with sodium valproate, chlorpromazine and haloperidol.

A nondiabetic young male patient in hypomanic phase of bipolar disorder on maintenance treatment with sodium valproate, developed transient episode of acute pancreatitis and diabetic ketoacidosis after addition of chlorpromazine and halopridol. It subsided completely within six weeks and his blood sugar was normal without any antidiabetic therapy. Simultaneous occurrence of acute pancreatitis and diabetic ketoacidosis is reported as a very rare complication of combination of antipsychotic drugs sodium valproate, chlorpromazine and haloperidol. Blood sugar should be periodically monitored in patients on sodium valproate and antipsychotic medication.

Acute Disease↗

PubMed2005

Sodium valproate -- induced skeletal myopathy.

The authors report a case of skeletal myopathy in a four-year-old boy on long-term sodium valproate therapy for secondary epilepsy due to neurocysticercosis. He presented with clinical features of limb girdle weakness. EMG revealed features of myopathy. Carnitine deficiency due to sodium valproate was suspected and plasma carnitine levels were found to be low. Sodium valproate was withdrawn. L-carnitine supplementation resulted in marked clinical recovery as well as rise in plasma carnitine levels.

Anticonvulsants↗

PubMed2005

Ultrastructural study of cerebellar dentate nucleus astrocytes in chronic experimental model with valproate.

The current study focuses on the morphogenesis of changes in the cerebellum dentate nucleus in the course of experimental valproate encephalopathy. Valproate - a broad spectrum antiepileptic and antipsychotic drug - chronically used in rats, intragastrically, once daily at a dose of 200 mg/kg b. w. for 1, 3, 6, 9 and 12 months, induced pronounced ultrastructural changes in the population of glial cells and nerve cells of the dentate nucleus of the cerebellum in the last two phases of the experiment. Astrocytic and neuronal lesions coexisted with a considerable damage to the elements of the blood-brain barrier of the cerebellar structure examined. The changes affected mainly the population of protoplasmic astrocytes lying loosely in a neuropile as well as astrocytes adhering to damaged large multipolar neurons. Focal proliferation of astrocytes was observed. Abnormal astrocytes showed marked swelling expressed by significantly decreased electron density of the cytoplasm that contained almost empty vacuolar structures and by a considerably reduced number of intracellular organelles. It was accompanied by dilation of endoplasmic reticular channels, loss of fibrillopoietic capacity of the cell and features of autophagocytosis. It should be assumed that the essential cause of protoplasmic astroglial damage of the cerebellar dentate nucleus could be associated, apart from the direct effect of valproate and/or its metabolites on these cells, with changes in structural elements of the blood-brain barrier of this CNS region.

Animals↗

PubMed1991

Valproate in combat-related posttraumatic stress disorder.

BACKGROUND: The symptoms of posttraumatic stress disorder (PTSD) suggest sympathetic nervous system hyperarousal and hyperreactivity. Pathophysiology of this condition may include stress-activated limbic kindling. Antikindling agents lithium and carbamazepine have been found effective for PTSD symptoms of intrusive reexperiencing and increased arousal. These facts suggest that valproate, another drug shown to interfere with limbic kindling, could also be effective for treatment of PTSD. METHOD: An open clinical trial of valproate was conducted in 16 Vietnam veterans diagnosed with DSM-III-R combat-related PTSD. RESULTS: Ten of 16 patients showed significant improvement, especially in hyperarousal/hyperreactivity symptoms. CONCLUSIONS: The efficacy of valproate in the treatment of PTSD should be rigorously studied.

Adult↗

PubMed1990

Valproate use in the older manic patient.

The authors present a case series of seven older (mean age = 66 years) state hospital patients treated with valproate as an adjunct to conventional medications. The patients had had affective disorder (chiefly bipolar disorder) for an average of 31 years. Most had been hospitalized at the state hospital for several years. Previous unsuccessful treatments had included lithium, carbamazepine, antipsychotics, benzodiazepines, and antidepressants and electroconvulsive therapy in one patient. After 1 month of adjunctive treatment, valproate led to marked improvement in three patients, moderate improvement in two, minimal improvement in one, and no change in one patient with delusional depression. Global Assessment Scale scores increased over baseline an average of 29 points (p = .01). Valproate proved to be safe in these older individuals, many of whom had several medical conditions.

Age Factors↗

PubMed1990

Valproate sodium in epilepsy. A clinical trial including monitoring of drug levels.

Sodium valproate was used as monotherapy in 90 cases with epilepsy who had at least one fit per week, irrespective of the type of seizures. The effect of the drug was evaluated on the basis of change in seizure frequency. Serum valproic acid levels were estimated by homogenous enzyme immunoassay. All the patients with absence (5/5) and myoclonic (3/3) seizures and 80% (42/53) of cases with generalized tonic-clonic seizures, became seizure free. Six of ten patients with only tonic seizures became seizure free. An average daily dose of 19.6 mg/kg provided a mean valproic acid level of 81.4 micrograms/ml in all seizure free patients. No correlation could be established between valproate dose and serum levels. Mild transient side effects were noted. No haematologic abnormality or hepatotoxicity was observed. Valproate sodium effectively controlled seizures in a majority of patients with partial seizures. Serum level monitoring helps to establish an optimal dose to keep the patient seizure free. No correlation could be established between side effects and serum levels.

Adolescent↗

PubMed1989

Valproate use in acute mania and bipolar disorder: an international perspective.

The author reviews European studies on the effect of the anticonvulsant agent valproate in the treatment of bipolar affective disorder. Since mania is associated with depletion of inhibitory transmitters in the central nervous system and gamma-aminobutyric acid (GABA) is one of the most important inhibitory transmitters, the GABAergic effects of valproate provide a theoretical basis for its use in affective disorders. The European studies, which have been both open and controlled, showed beneficial effects of valproate in acute and prophylactic treatment of bipolar illness, with particularly good results in mania. Side effects reported most often were mild and transient, and included gastrointestinal upset, lethargy, increased levels of hepatic transaminases, and mild alopecia.

Acute Disease↗

PubMed1989

Phenomenology of rapid cycling manic depression and its treatment with valproate.

Although the recurrent nature of manic depressive illness has been recognized since the time of Kraepelin, it has only recently been noted that this feature of the illness has prognostic significance. A subgroup of patients who experience more than four major mood swings per year has been identified as rapid cyclers and are now believed to account for a significant proportion of treatment resistance. In some instances, such rapid cycling is believed to be not only exacerbated by but possibly caused by the use of conventional unimodal antidepressants such as tricyclics. For this reason, the routine use of such antidepressants should be considered ill-advised until patients have been shown to be resistant to lithium's acute antidepressant properties. Although lithium remains the initial treatment of choice for manic depression, a substantial majority of manic depressive patients prove to be lithium-resistant and a growing body of data suggests this refractory group is accompanied by a disproportionate amount of frequent mood swings. When the lithium-resistant bipolar patient is encountered, the addition of one of two anticonvulsants, either valproate or carbamazepine, often provides significant therapeutic effects. Both valproate and carbamazepine appear to be similarly effective, but valproate may be better tolerated and easier to use.

Bipolar Disorder↗

PubMed1989

Valproate in anxiety and withdrawal syndromes.

Various anticonvulsant medications may have efficacy in the treatment of certain anxiety states as well as withdrawal syndromes occurring after the discontinuation of sedative-hypnotic drugs and alcohol. Preclinical studies and limited anecdotal evidence suggest that valproate may be more effective in controlling panic than carbamazepine. In small studies valproate and carbamazepine have been shown as possible effective agents in the treatment of alcohol withdrawal. Some treatment-resistant patients with panic disorder may respond well to trials of certain anticonvulsants. It is also possible that some patients in the heterogeneous generalized anxiety disorder category may respond to valproate and carbamazepine, particularly in light of the similarity between this type of anxiety and the symptoms of alcohol and sedative-hypnotic drug withdrawal. While benzodiazepines clearly have an important role in the treatment of anxiety and withdrawal states, the role of nonbenzodiazepine anticonvulsants is a promising one which needs to be further delineated with careful, controlled studies.

Adult↗

PubMed1989

Effects of carbamazepine, valproate calcium, clonazepam and piracetam on behavioral test methods for evaluation of memory-enhancing drugs.

The effect of three anticonvulsants on several test methods for evaluation of memory-enhancing drugs have been studied in rats and mice. The results were compared to the results obtained from the nootropic piracetam and from imipramine. In an active avoidance test (pole jumping), repeated administration of carbamazepine (5 mg/kg i.p.) and piracetam (300 mg/kg p.o.) protected against impairment of learning rate caused by repeated application of an electroconvulsive shock. Valproate calcium (repeated administration of 30 mg/kg i.p.) was only weakly active, while clonazepam (repeated administration of 0.3 mg/kg i.p.) decreased the learning rate even more. Drugs were given in dosages which have no anticonvulsive activity in this test. The impairment of learning rate caused by repeated application of ethanol was prevented by carbamazepine (5 mg/kg i.p.), valproate calcium (30 and 100 mg/kg i.p.) and piracetam (100 mg/kg i.p.). Clonazepam (0.3 and 1 mg/kg i.p.) had a worsening effect on learning rate. In Porsolt's behavioral despair test, carbamazepine (5, 10 and 30 mg/kg i.p.) and valproate calcium (30 and 100 mg/kg i.p.) shortened the duration of immobility, which indicates an increased psychomotor activity. Clonazepam was ineffective. Results obtained with carbamazepine are similar to those obtained with piracetam. The data are discussed in view of the so-called psychotropic effects of carbamazepine in clinical trials.

Animals↗

PubMed1989

The effect of magnesium valproate on plasma ACTH concentrations in Nelson's syndrome.

Sodium valproate, a gamma-aminobutyric acid (GABA) agonist, was found to decrease plasma ACTH concentration in some cases of Cushing's disease and Nelson's syndrome. In this study we have investigated the influence of magnesium valproate (MV), a newly introduced salt of valproic acid, on plasma ACTH levels in 8 patients with Nelson's syndrome. The daily dose, 1200 mg of MV, significantly decreased plasma ACTH level at 10 p.m. compared with placebo. A single dose of 400 mg of MV, led to a reduction in plasma ACTH concentration only in two out of seven patients during a four-hour observation. The fall in plasma ACTH level in the same patients at 10 p.m., after the next two doses of this drug, suggests that single dose may be insufficient for introducing GABA-dependent reduction in ACTH release. During a long-term therapy with MV, in all three patients investigated a marked decrease in plasma ACTH was observed. Our results suggest that magnesium valproate may be useful during chronic therapy in some patients with ACTH hypersecretion.

Adrenocorticotropic Hormone↗

PubMed1989

Treatment of resistant schizophrenia with valproate and neuroleptic drugs.

Four cases of resistant Schizophrenia treated with valproate association with different neuroleptic drugs (thioridazine in three cases and loxapine in one) are presented. After a mean period of three months with this treatment, clinical improvement, consisting in a reduction of positive symptoms, as measured by the BPRS, and a normalization of hostile/disruptive behavior, was observed, and hospital discharge was possible. Reduction of symptoms was still present after a follow-up of 4 to 24 months. As valproate is a drug with gabaergic properties, a GABA involvement in the pathogenesis of schizophrenia is discussed. The association of valproate to neuroleptic drugs should be considered in the treatment of resistant Schizophrenia.

Adult↗

PubMed1985

Etifoxine: evaluation of its anticonvulsant profile in mice in comparison with sodium valproate, phenytoin and clobazam.

The anticonvulsant potential of 6-chloro-2-(ethylamino)-4-methyl-4-phenyl-4H-3,1-benzoxazine (etifoxine), a non-benzodiazepine tranquilizer, was evaluated in mice in comparison to valproate, phenytoin and clobazam. Maximal seizures were induced by electroshock (MES) and the chemical convulsants pentetrazol (PTZ), picrotoxin (PTX), bicuculline (BIC), isoniazid (INH), nicotine (NIC) and strychnine (STR). Tonic extensor convulsions were prevented by etifoxine in the following rank order of potency (ED50 values with seizure tests): 39.5 (PTX), 101 (PTZ), 101 (MES), 154 (INH), 181 (NIC), 397 (BIC), and greater than 800 mg/kg p.o. (STR). Clonic seizures were induced by threshold doses of PTZ, PTX and pilocarpine (PIL) and antagonized by etifoxine at ED50 values of 181 (PIL), 221 (PTZ), and greater than 800 mg/kg p.o. (PTX). Hence, etifoxine blocked both tonic and clonic seizures but was more potent against the tonic component. The anticonvulsant profile of etifoxine appeared similar to that of valproate. However, in terms of potency, protective indices (ED50 rotarod/ED50 seizure test) and therapeutic indices (LD50/ED50 seizure test) etifoxine was on an average 3.7, 12 and 14 times superior to valproate, respectively. It is concluded that etifoxine has a marked anticonvulsive potential and may be beneficially used in epileptic disorders, especially of the grand mal type.

Animals↗

PubMed1985

[Anxiolytic action of sodium valproate (possible role of gamma-aminobutyric acid in affective disorders)].

An experimental and clinico-pharmacological study of sodium valproate, a GABA-ergic drug, was conducted to elucidate the role of gamma-aminobutyric acid in the mechanisms responsible for affective disturbances, in particular for anxiety. A tranquilizing effect of the drug, comparable with the action of diazepam, was established in a conflict situation model in experimental animals. Using clinico-psychological methods the authors showed a distinct tranquilizing action of valproate in patients suffering from neurotic and neurosis-like disorders with manifestations of anxiety in the structure of the psychopathological syndrome. It was established that this action was accompanied by no manifestations of myorelexation, ataxia or somnolence characteristic of tranquilizers of the benzodiazepine series. The presence of tranquilizing properties in the GABA-ergic drug sodium valproate confirms the suggestion that a certain relationship exists between the GABA system and anxiety.

Adult↗

PubMedDate not supplied

[Experimental study of the antiepileptic activity of fenibut and its combinations with sodium valproate and aminooxyacetic acid].

The antiepileptic activity of GABA-mimetics (phenibut, sodium valproate and aminooxyacetic acid/AOAA/) was studied in experiments on the model of hippocampal penicillin-induced epilepsy in rats. The effects of the drugs were studied in experiments with a mirror epileptogenic focus which forms in the hippocampus contralateral to the penicillin-damaged hippocampus. All the drugs suppressed the activity of the epileptogenic focus after injections in the focus region. At systemic administration of the drugs the antiepileptic activity was found only with sodium valproate and AOAA. Phenibut enhanced the antiepileptic effect of sodium valproate and the toxic effects of AOAA at parenteral administration.

Acetates↗