Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amygdala-kindled rats were treated with valproic acid (VPA; administered as its sodium salt) 3 times daily at 200 mg/kg i.p. for 6 weeks, and anticonvulsant and adverse effects during this period were studied. Groups of nonkindled rats were treated in parallel for determination of VPA and its major active metabolites in various brain regions after different durations of treatment. After the first injection of VPA, 200 mg/kg, seizure severity, seizure duration and duration of electrical afterdischarges recorded from the stimulated amygdala were reduced significantly, but only one of nine animals was protected completely from kindled seizures. At day 3 of chronic treatment, the anticonvulsant activity of VPA had increased markedly so that seven of nine animals were totally protected from seizures. However, this potent anticonvulsant effect was only transitory so that after 1 week of treatment the anticonvulsant effect of the medication was similar to that obtained after the first dosing. The effect of VPA remained at this level for the subsequent weeks, but there was a second, more permanent increase in the number of protected animals after 4 to 6 weeks. Plasma and brain levels of VPA and its metabolites remained relatively constant throughout the chronic treatment although there was a moderate accumulation of some metabolites, e.g., trans isomer of 2-propyl-2-pentenoic acid, in specific brain nuclei. The most prominent adverse effects of VPA were ataxia, muscle relaxation, wet-dog shake behavior and an increase in body temperature. Except for body temperature, tolerance developed to these adverse effects, but escape from wet-dog shake behavior occurred much more rapidly than reduction of other adverse effects. Pathohistological examination of liver sections from animals treated with VPA for 6 weeks showed no indication of any hepatotoxic effects. After drug withdrawal, kindled seizure parameters returned toward control values without evidence of significant carry-over effects. Five days after termination of treatment, only minute amounts of VPA and trans isomer of 2-propyl-2-pentenoic acid were determined in some brain regions, indicating that there was no persistence of active drug or metabolite concentrations in the brain.
 ...
PMID:Valproic acid in amygdala-kindled rats: alterations in anticonvulsant efficacy, adverse effects and drug and metabolite levels in various brain regions during chronic treatment. 250 34

Thirty two patients with juvenile myoclonic epilepsy are described. The most relevant aspects of the disease are the following: it starts at nearly 12 years of age or before; it is frequently associated with generalized tonic-clonic seizures; myoclonic and tonic-clonic seizures occur at time of awaking or shortly after; no pathological findings occur at the central nervous system; a large number of relatives show generalized seizures and the interictal electroencephalogram is usually disturbed by generalized epileptic activity. Valproic acid, preferably alone, is probably the treatment of choice for these patients.
 ...
PMID:[Juvenile myoclonic epilepsy: Janz' syndrome]. 251 65

The duration of protective action of valproate (VPA, 400 mg/kg i.p.) against metrazol-induced seizures was studied in rats aged 7, 12, 18 and 90 days. Fifteen, protected. The results differed between the various age groups after longer intervals: The protection was longest in 18-day-old rats--seizures did not appear even six hours after VPA administration. On the contrary, all 7-day-old rat pups exhibited seizures two hours after VPA. Plasma levels of VPA were measured by means of gas chromatography in the same age groups after an identical dose of VPA. After a single injection of VPA a clear-cut two-peak curve of plasma level was found in all young groups, which may be due to an enterohepatic recirculation of VPA. The maximum plasma levels were lowest in 7-day-old rats, the three older groups exhibited similar values. Plasma half-life was longest in the youngest animals (9.24) and decreased with age; values for 18- and 901 day-old rats did not differ (2.57 and 3.05 h respectively). No clear-cut correlation was found between the antimetrazol action and its plasma levels.
 ...
PMID:Antimetrazol action and plasma levels of valproate in developing rats. 252 63

The Lennox-Gastaut Syndrome is one of the most refractory form of epilepsy and a variety of compounds, such as traditional antiepileptics, "new anticonvulsants" and non-anticonvulsant drugs has been tested. ACTH and, among the traditional antiepileptics. Clonazepam and Sodium Valproate showed the most favorable effects. The immediate (within 6 months) therapeutic response to ACTH and Clonazepam is satisfactory, with a more than 50% reduction of seizures in about one half of patients; after one year, however, only a small percentage of cases (7-10%), rather close to that with spontaneous remission, shows some therapeutic benefit. Valproate, when used as a single drug, produces a decrease in seizures (greater than 50%) in 25-30% of pts. A list of compounds, such as amphetamine, taurine, amantadine, allopurinol and, among the new putative antiepileptics, cinromide and gamma-vinyl-GABA, has been tested with some occasionally observed improvement in seizure control. None of these compounds, however, is of really proven efficacy. An acquired general rule of treatment is to avoid complex polypharmacy and overdose; there is in fact good evidence that making the child drowsy will greatly increase the number of fits.
 ...
PMID:[Lennox-Gestaut syndrome: therapeutic aspects]. 270 Aug 41

Common antiepileptic drugs and agents affecting different neurotransmitter systems were studied against aminophylline (280 mg/kg i.p.)-induced convulsions in mice. All drugs and agents were administered i.p. Diazepam and phenobarbital antagonized the whole seizure pattern and the respective ED50 values for the clonic phase were 3.5 and 62 mg/kg. Valproate at 500 mg/kg protected fewer than 50% of mice against the clonic phase. The remaining antiepileptics (acetazolamide, up to 1,000 mg/kg; carbamazepine and diphenylhydantoin, up to 50 mg/kg; ethosuximide, 500 mg/kg and trimethadione, 400 mg/kg) were totally ineffective in this respect. Propranolol (up to 20 mg/kg), baclofen (20 mg/kg), gamma-hydroxybutyric acid (300 mg/kg), aminooxyacetic acid (20 mg/kg), clonidine (up to 0.2 mg/kg), ketamine (30 mg/kg), atropine (20 mg/kg), papaverine (50 mg/kg) and L-phenylisopropyladenosine (2 mg/kg) did not affect the clonic phase either. Only antagonists of N-methyl-D-aspartic acid excitation, 2-amino-5-phosphonopentanoic acid and 2-amino-7-phosphonoheptanoic acid afforded protection against aminophylline-induced clonic seizure activity. The results show that aminophylline convulsions are relatively resistant to antiepileptic drugs and suggest that antagonists of excitatory transmission are potential antiaminophylline drugs.
 ...
PMID:Inhibition of aminophylline-induced convulsions in mice by antiepileptic drugs and other agents. 283 Oct 68

Somatostatin and gamma-aminobutyric acid (GABA) concentrations were evaluated in the brain of kindled rats treated chronically with carbamazepine and valproic acid. Kindled seizures were almost completely blocked by treatment with carbamazepine, whereas the effect of valproic acid was partial, suppressing only generalized seizures. The duration of after-discharge in amygdala was suppressed by carbamazepine not by valproic acid. Carbamazepine induced a decrease in immunoreactive somatostatin concentration and an increase in GABA concentration in the temporal cortex of kindled rats. Valproic acid induced only an increase in GABA concentration. The results suggest that somatostatin may be associated with the suppression of focal seizure in amygdala and GABA may have a role in the suppression of generalized seizures.
 ...
PMID:Effects of carbamazepine and valproic acid on brain immunoreactive somatostatin and gamma-aminobutyric acid in amygdaloid-kindled rats. 287 90

Influence of ethosuximide (ESI, 125 mg/kg i.p.) and dipropylacetate (DPA, 300 mg/kg i.p.) pretreatment on electrocorticographic changes induced by pentamethylenetetrazole (PTZ, 20 mg/kg dose every 5 min) was studied in rats aged 7, 12, 18 and 90 days. PTZ alone induced isolated spikes and/or sharp waves as the first sign of its action in all age groups except in adult animals where rhythmic theta activity was elicited. The antiepileptic effect of DPA was observed in 12- and 18-day-old rats, ESI specifically inhibited rhythmic activity in adult rats. ECoG seizures induced by high doses of PTZ were inhibited by DPA in all age groups, ESI tended to be effective in adult rats only. DPA did not change the pattern of ECoG seizures, whereas ESI led to replacement of the spike-and-wave rhythm by serrated waves in adult animals. The low ability of immature brain to generalize ictal activity was further diminished by ESI.
 ...
PMID:Influence of ethosuximide and dipropylacetate on metrazol-induced electrocorticographic changes during ontogenesis in rats. 294 8

The authors report the results obtained in 42 patients affected by infantile spasms syndrome during treatment with Sodium Dipropylacetic acid. The subjects were divided into two groups according to the aetiology: idiopathic and secondary. In the first group the use of DPK as determined the disappearance of the seizures in 6 cases (40%), reduction of the crises beyond 50% in 7 cases (46.6%), while in 2 subjects (13.3%) the crises persisted. In the secondary group the crises ceased in 3 cases (11.1%), in 17 (62.9%) there were a reduction of the crises beyond 50%, no response to the drug was observed in 7 subjects (25.9%). In 10 patients the anticonvulsant treatment was progressively diminished and was substituted with hormonal treatment. The long term follow up (1-6 years) gives the following results: the seizures persisted in 2 cases (18.18%) among the idiopathic form and in 6 cases (28.57%) among the secondary group. Mental retardation was found in 4 subjects (36.36%) among the idiopathic group and in 12 patients (57.14%) among the secondary group. The authors shortly report the side effect of the hormonal treatment: they prefer the initiation of treatment of I.S. with anticonvulsant drug and suggest to resort to the ACTH when the initial treatment is unsuccessful.
 ...
PMID:[Therapy of infantile spasms (West syndrome) with sodium dipropylacetate]. 301 74

Two patients complained of myoclonic jerks precipitated by writing. They had suffered only sporadic seizures triggered by reading. Laboratory assessment demonstrated that typing was the most powerful stimulus in triggering spike-wave discharges associated with myoclonic seizures. Sodium Valproate (20 mg/Kg/die) led to a complete remission of seizures in both cases.
 ...
PMID:Writing epilepsy. 308 39

Ethosuximide is the drug of first choice in absence seizures. Idiosyncratic side effects are rare. Valproate is effective against absence, generalized tonic-colonic, and partial seizures. It is the drug of choice in photosensitive seizures. Valproate is, on the whole, free from unpleasant side effects, but fatal hepatotoxicity and hyperamnionemia have been reported very rarely.
 ...
PMID:Use of ethosuximide and valproate in the treatment of epilepsy. 309 3


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>