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)

Since gamma-hydroxybutyric acid (GHB) is known to be an effective anesthetic adjuvant in animal and a natural metabolite of succinic semialdehyde (SSA), the effect of SSA and GHB on the convulsive action of vitamin B6 antagonists was studied using the onset of seizure as a parameter. The administration of SSA and GHB to mice protected them against the convulsive action of B6 antagonist, such as castrix (2-chloro-4-dimethyl-6-methylpyrimidine), thiosemicarbazide, or penicillamine. The anticonvulsant effect of SSA seems to be due to an increase in brain levels of GHB converted in vivo from SSA.
 ...
PMID:Effect of succinic semialdehyde on seizure caused by vitamin B6 antagonists. 101 Oct 43

We have investigated whether the pathogenesis of spontaneous generalized non-convulsive seizures in rats with genetic absence epilepsy is due to an increase in the brain levels of gamma-hydroxybutyric acid (GHB) or in the rate of its synthesis. Concentrations of GHB or of its precursor gamma-butyrolactone (GBL) were measured with a new GC/MS technique which allows the simultaneous assessment of GHB and GBL. The rate of GHB synthesis was estimated from the increase in GHB levels after inhibition of its catabolism with valproate. The results of this study do not indicate significant differences in GHB or GBL levels, or in their rates of synthesis in rats showing spike-and-wave discharges (SWD) as compared to rats without SWD. Binding data indicate that GHB, but not GBL, has a selective, although weak affinity for GABAB receptors (IC50 = 150 microM). Similar IC50 values were observed in membranes prepared from rats showing SWD and from control rats. The average GHB brain levels of 2.12 +/- 0.23 nmol/g measured in the cortex and of 4.28 +/- 0.90 nmol/g in the thalamus are much lower than the concentrations necessary to occupy a major part of the GABAB receptors. It is unlikely that local accumulations of GHB reach concentrations 30-70-fold higher than the average brain levels. After injection of 3.5 mmol/kg GBL, a dose sufficient to induce SWD, brain concentrations reach 240 +/- 31 nmol/g (Snead, 1991) and GHB could thus stimulate the GABAB receptor. Like the selective and potent GABAB receptor agonist R(-)-baclofen, GHB causes a dose-related decrease in cerebellar cGMP. This decrease and the increase in SWD caused by R(-)-baclofen were completely blocked by the selective and potent GABAB receptor antagonist CGP 35348, whereas only the increase in the duration of SWD induced by GHB was totally antagonized by CGP 35348. The decrease in cerebellar cGMP levels elicited by GHB was only partially antagonized by CGP 35348. These findings suggest that all effects of R(-)-baclofen are mediated by the GABAB receptor, whereas only the induction of SWD by GHB is dependent on GABAB receptor mediation, the decrease in cGMP being only partially so. Taken together with the observations of Marescaux et al. (1992), these results indicate that GABAB receptors are of primary importance in experimental absence epilepsy and that GABAB receptor antagonists may represent a new class of anti-absence drugs.
 ...
PMID:Experimental absence seizures: potential role of gamma-hydroxybutyric acid and GABAB receptors. 132 78

gamma-Hydroxybutyric acid (GHB), a naturally occurring compound which is synthesized from gamma-aminobutyric acid (GABA), induces bilaterally synchronous spike wave discharges, associated with behavioral changes, reminiscent of petit mal or generalized absence seizures in rats. In the present study, possible involvement of excitatory amino acids (EAAs) in GHB-induced spike wave discharges was investigated. The noncompetitive antagonist of NMDA receptors, MK-801, attenuated GHB-induced spike wave discharges at all doses tested (0.025-1.0 mg/kg) but dose-dependently induced suppression of EEG bursts in GHB-treated animals. The suppression of bursts was never observed with GHB in control experiments. N-Methyl-D-aspartate (NMDA) had a similar effect on GHB-induced spike wave discharges, when it was administered prior to GHB. This effect of NMDA was partially reversed by MK-801. The competitive antagonists of NMDA receptors, (+/-)CPP and CGP 43487 and the antagonist at the strychnine-insensitive glycine site, HA-966, also suppressed GHB-induced spike wave discharges with the EEG progressing to suppression of bursts but were weaker in this regard than MK-801 or NMDA. These data raise the possibility of involvement of excitatory amino acids in the GHB model of absence seizures.
 ...
PMID:Involvement of excitatory amino acid mechanisms in gamma-hydroxybutyrate model of generalized absence seizures in rats. 143 82

gamma-Hydroxybutyric acid (GHB) produces a constellation of EEG and behavioral changes when given to animals, which represent an experimental model of generalized absence seizures. gamma-Butyrolactone (GBL), the prodrug of GHB, produces these changes more rapidly and consistently than GHB, such that the rat treated with GBL is a more reproducible and predictable model of absence seizures. The hypothesis that the epileptogenic effects of GBL are due solely to its conversion to GHB was tested. The regional concentration of both compounds in brain was determined in time-course and dose-response studies, as well as at the onset of EEG changes, induced by both GHB and GBL. Also, the EEG and behavioral effects of both drugs were ascertained after intrathalamic injection in the rat. gamma-Butyrolactone produced a rapid onset of bilaterally synchronous spike and wave discharges in the rat, which correlated with a rapid appearance of GHB in brain in the GBL-treated animals. In the GHB-treated animals, EEG changes occurred 20 min after administration of GHB when levels of GHB in the brain were peaking. The threshold concentration of GHB in brain for EEG changes, in both GHB-and GBL-treated animals was 240 x 10(-6) M. The concentration of GBL in brain peaked 1 min after administration of GBL and fell rapidly to undetectable levels within 5 min. Bilateral injection of GHB into thalamus resulted in a brief burst of spike and wave discharges, while GBL, administered into the thalamus, had no effect. The use of GBL as a prodrug for GHB in this model of generalized absence seizures is valid, since GBL itself was inactive.
 ...
PMID:The gamma-hydroxybutyrate model of absence seizures: correlation of regional brain levels of gamma-hydroxybutyric acid and gamma-butyrolactone with spike wave discharges. 203 Aug 21

Synthesis and properties of new N-substituted amides of alpha-(1,1-ethylenedioxy)-ethyl-gamma-hydroxybutyric acid are described. The compounds were obtained by aminolysis of 3-(1,1-ethylenedioxy)-ethyltetra-hydrofuran-2-on with primary alkylarylamines. Preliminary pharmacological assessment revealed that the compounds exert weaker influence on the central nervous system than the reference gamma-hydroxybutyric acid. Three of the novel compounds offered some protection against pentetrazole-induced tonic seizures in mice.
 ...
PMID:Synthesis and preliminary pharmacological assessment of novel gamma-hydroxybutyric acid derivatives. 209 56

Impairment of motor coordination by the excitatory amino acid antagonists 2-amino-7-phosphonoheptanoic acid (APH) and glutamic acid diethyl ester (GDEE) was measured and compared to GABA agonists and anticonvulsants and other compounds by the Coughenour inverted screen test. The GABA agonists muscimol and imidazole acetic acid, and the GABA analogue gamma-hydroxybutyric acid were found to produce a marked impairment of motor coordination. The dosages of phenytoin and valproate which impaired motor coordination, on the other hand, were considerably above the dosages which have been reported to inhibit seizures. APH caused motor incoordination at a dosage of 125 mg/kg, and a prolonged motor impairment was present after administration of APH, 250 mg/kg. GDEE did not significantly impair motor coordination in any dosage tested up to 1920 mg/kg. These results further encourage development of more potent GDEE-like compounds as potential anticonvulsants.
 ...
PMID:Impaired motor coordination in mice induced by 2-amino-7-phosphonoheptanoic acid (APH), glutamic acid diethyl ester (GDEE), and other compounds. 274 Apr 26

The ability of gamma-hydroxybutyric acid to suppress ethanol withdrawal syndrome was tested in male rats rendered physically dependent on ethanol by several intragastric administrations of ethanol (9-15 g/kg daily for 7 days). Gamma-hydroxybutyrate (0.25, 0.50 and 1.00 g/kg i.p.), administered 8 hr after the last ethanol dose, produced a dose-dependent inhibition of withdrawal signs such as tremors and audiogenically-induced seizures; the highest dose tested suppressed all ethanol withdrawal symptoms.
 ...
PMID:Suppression by gamma-hydroxybutyric acid of ethanol withdrawal syndrome in rats. 281 52

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

With microwave diathermy, febrile seizures were produced in epileptic chicks aged 2-5 days. Drugs that enhance GABAergic activity (i.e., GABA, muscimol, and progabide), as well as valproic acid and gamma-hydroxybutyric acid, produced dose-dependent increases in latency to onset of seizures.
 ...
PMID:Protection by GABA agonists, gamma-hydroxybutyric acid, and valproic acid against seizures evoked in epileptic chicks by hyperthermia. 314 60

The specific opiate antagonists--naloxone and naltrexone--attenuated or abolished the electrical seizure activity, behavioral abnormalities, and increased striatal dopamine content produced by gamma-butyrolactone, the prodrug of gamma-hydroxybutyrate. The effects of naloxone and naltrexone were dose-dependent. These data suggest that gamma-hydroxybutyric acid exerts its effects by action either at the opiate receptor or on enkephalinergic systems, which may be involved in petit mal epilepsy.
 ...
PMID:Naloxone overcomes the dopaminergic, EEG, and behavioral effects of gamma-hydroxybutyrate. 719 Oct 65


1 2 3 4 5 6 Next >>