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)

The possibility that a sex difference in gamma-aminobutyric acid (GABA) activity might be an underlying cause of the previously reported sex differences in picrotoxin-induced seizures was investigated. Male and female rats were injected (IP) with the GABA antagonist, L-allylglycine (100, 150, 200, or 250 mg/kg), and observed for behavioral signs of five categories of seizures induced by picrotoxin: myoclonic, focal, generalized tonic extension, generalized clonic, and generalized seizures with tonic and clonic components. The latency to the first occurrence of each seizure category was scored. Of the five categories of seizures investigated, only focal and generalized tonic extension seizures were observed after allylglycine in the doses tested. Female rats were significantly more susceptible than male rats to allylglycine-induced focal (p less than 0.007) and generalized tonic extension (p less than 0.05) seizures. The results suggest that male-female differences in presynaptic GABA activity may have relevance for sex differences in the occurrence of focal and tonic extension seizures. Differences in the seizure profiles associated with allylglycine and picrotoxin suggests that pre- and postsynaptic antagonism of GABA activity may have different consequences for specific seizure categories and the sex differences associated with those categories.
 ...
PMID:Allylglycine-induced seizures in male and female rats. 165 71

Characteristics of muscarinic cholinergic (mACh), gamma-aminobutyric acid(A) (GABAA) and phencyclidine (PCP) receptors in the spontaneously epileptic rats (SER), which exhibit both absence-like seizures and tonic convulsion, were examined using in vitro quantitative autoradiography. Computer analysis using autoradiographic technique revealed that the amount of the specific binding of [3H]quinuclidinyl benzilate (QNB) to mACh receptors in the striatum of SER was more than that of zitter rats, not exhibiting both seizures and convulsion. However, the specific bindings of [3H]muscimol and [3H]N-(1-[2-thienyl]cyclohexyl)3,4-piperidine (TCP) to GABAA and PCP receptors, respectively, of SER were not different from those of zitter rats in various regions tested. These results suggest that hyperfunction of mACh receptors in the striatum is involved in the appearance of absence-like seizures and tonic convulsion of SER.
 ...
PMID:Characteristics of muscarinic cholinergic, gamma-aminobutyric acid(A) and phencyclidine receptors in spontaneously epileptic rats; in vitro quantitative autoradiographic analysis. 166 11

The release of putative neurotransmitters [aspartate, glutamate, and gamma-aminobutyric acid (GABA)] was studied in hippocampal slices from adult normal C57BL/6J (B6) and El (epileptic) mice. The El mice, a genetic model of temporal lobe epilepsy, had an average of 86 seizures. Sets of B6 and El hippocampal slices (400 microns thick) were incubated in a series of normal and high potassium (60 mM) buffers in the presence or absence of calcium. The calcium-dependent and calcium-independent potassium-induced release of amino acids was compared in each mouse strain. Release of endogenous amino acids was measured using liquid chromatography with electrochemical detection and was expressed as picomoles of amino acid released per milliliter of incubation buffer per minute of incubation per slice +/- SEM. No significant differences were found between the El and B6 mice for the calcium-dependent potassium-evoked release of glutamate (18.20 +/- 2.62 and 15.41 +/- 3.56), or GABA (17.28 +/- 2.90 and 12.73 +/- 1.37), respectively. Aspartate release, however, was significantly higher in the El mice (6.62 +/- 0.69) than in the B6 mice (3.31 +/- 0.72). These findings suggest that enhanced aspartate release may be related to seizure expression in El mice.
 ...
PMID:Enhanced aspartate release from hippocampal slices of epileptic (El) mice. 167 82

Stimulation of the perforant path, a major input to the hippocampal formation, produced significant decreases in the hippocampal levels of methionine enkephalin, dynorphin A(1-8) and an increase in the hippocampal level of gamma-aminobutyric acid. In addition, it was also observed that both mu and delta opioid receptor antagonists reduce wet dog shakes elicited by perforant path stimulation. The antagonists did not affect the changes in hippocampal levels of methionine enkephalin, dynorphin A(1-8) or gamma-aminobutyric acid. The results demonstrate that endogenous opioids are involved in the wet dog shakes elicited by perforant path stimulation. Since electrographic seizure activity occurs in the hippocampus in conjunction with perforant path stimulation-induced wet dog shakes, these data provide further evidence that endogenous opioid peptides play an important role in regulation of limbic system epileptogenic phenomena.
 ...
PMID:Opioid mu and delta receptor antagonists reduce wet dog shaking elicited by perforant path stimulation. 167 26

Lamotrigine (LTG), a new anticonvulsant, chemically unrelated to current antiepileptic drugs (AEDs), resembles phenytoin (PHT) and carbamazepine (CBZ) in ability to block hindlimb extension in both the maximal electroshock test and leptazol-induced seizures. Results indicate that LTG may be of value in both partial and generalized seizures. In in vitro studies, LTG has been shown to inhibit veratrine-evoked release of glutamate when a threshold depolarizing concentration (4 micrograms/ml) is used, and also inhibits aspartate release when a larger stimulus is given (10 micrograms/ml). However, LTG does not block potassium-evoked transmitter release. LTG is a less potent inhibitor of the release of gamma-aminobutyric acid (GABA), acetylcholine, noradrenaline, and dopamine. LTG blocks the neurotoxicity of kainic acid in vivo, supporting the in vitro findings, and suggests that the anticonvulsant effect of LTG may be due to inhibition of glutamate release. In a test of working memory and phencyclidine (PCP) discrimination studies, LTG had no effect, indicating no sharing of the same PCP-like side effects associated with NMDA receptor blockade. In the gerbil model of global ischemia, high doses of LTG provided protection against damage to the CA1 region of the hippocampus. Analogues of LTG of higher potency to block the release of glutamate may be necessary to ensure protection against ischemic brain damage.
 ...
PMID:Neurochemical and behavioral aspects of lamotrigine. 168 39

1. Sodium di-n-propylacetate (DPA) treatment induced significant increases in brain contents of gamma-aminobutyric acid (GABA), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA). Furthermore, the threshold for pentylenetetrazol (PTZ) clonic convulsions was also increased in response to DPA administration. 2. Pretreatment with inhibitors of monoamine synthesis alpha-methyl-p-tyrosine (AMPT) and p-chlorophenylalanine (PCPA) did not alter the anticonvulsant activity of DPA, but when given alone, both AMPT and PCPA caused significant decreases in brain monoamine contents and PTZ threshold seizures. 3. Experiments using probenecid suggest that the increases in 5-HIAA and HVA seen after DPA treatment could have resulted from inhibition of their active transport out of the brain. These data indicate that the anticonvulsant action of DPA is not dependent on changes in monoamine metabolism in the brain.
 ...
PMID:Anticonvulsant activity of di-n-propylacetate and brain monoamine metabolism in the rat. 169 53

The chronic epileptic syndrome induced by injecting tetanus toxin into rat hippocampus causes functional changes that essentially are permanent, outlasting the period of active seizures by at least 1 year. These long-term changes have been characterized by an impaired performance on a range of behavioral tasks, which in turn have been associated with a physiologic depression of hippocampal evoked responses but not with any discernible histopathology. In the present study, we examined the hippocampi of rats in the postseizure phase of the tetanus toxin model and observed no significant changes in the concentration of neurochemical markers for six neurotransmitters. Therefore, the long-term reduction in hippocampal excitability cannot be attributed to any major loss of afferents or hippocampal neurons using aspartate, acetylcholine, gamma-aminobutyric acid (GABA), glutamate, norepinephrine (NE), or serotonin as their transmitters.
 ...
PMID:Lack of change in neurochemical markers during the postepileptic phase of intrahippocampal tetanus toxin syndrome in rats. 170 Sep 50

Vigabatrin was specifically designed to enhance gamma-aminobutyric acid (GABA) function in the CNS. By increasing brain concentrations of this inhibitory neurotransmitter the drug appears to decrease propagation of abnormal hypersynchronous discharges, thereby reducing seizure activity. At this stage in its development, clinical experience with vigabatrin is limited primarily to patients with refractory seizure disorders. In this difficult-to-treat population, 'add-on' therapy with vigabatrin greater than or equal to 2 g/day has shown impressive efficacy, reducing seizure frequency by greater than or equal to 50% in approximately half of patients. Clinical efficacy does seem to vary with seizure type with the best response reported in adults with complex partial seizures with or without generalisation and in children with cryptogenic partial epilepsy or symptomatic infantile spasm. Vigabatrin appears to have a negative effect on absences and myoclonic seizures. Some disorders of motor control may also be amenable to enhanced GABAergic function. In the small number of patients with tardive dyskinesia treated to date, vigabatrin produced mild to moderate improvement in hyperkinetic symptom scores but Parkinsonism or schizophrenic symptoms occasionally worsened. The best response was reported in a study of patients who had been withdrawn from neuroleptic therapy. In a small but well-controlled comparative trial, vigabatrin was as effective as baclofen in reducing spasm and improving some parameters of spasticity in patients with spinal cord lesions or multiple sclerosis. Most adverse reactions to vigabatrin are mild and transient with central nervous system (CNS) changes being reported most frequently. Of particular note, serial evoked potential studies and the few available histology reports have not found evidence of intramyelinic oedema during therapeutic use, as was reported in rats and dogs on chronic high-dose treatment. Thus, vigabatrin is a promising new anticonvulsant drug. Current evidence supports a trial of this agent as adjunctive therapy in patients with refractory seizure disorders, and future investigation of vigabatrin monotherapy and its efficacy relative to established agents is awaited with interest. Wider experience should help to clarify which patients - by seizure type and concurrent CNS pathology - are likely to benefit from vigabatrin and ongoing monitoring should further clarify the potential detrimental effects, if any, of long term use. In the meantime, it is a welcome addition in the difficult setting of resistant epilepsy.
 ...
PMID:Vigabatrin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in epilepsy and disorders of motor control. 171 66

Autopsy study of a patient who died after an episode of prolonged unilateral status epilepticus revealed neuronal loss in the hippocampus on the epileptic side, with gliosis confined to the CA1 and CA3 fields. There was loss of the parvalbumin-immunoreactive gamma-aminobutyric acid (GABA)-ergic interneurons in the hippocampus on that side. There was also loss of the normal laminar pattern of substance P staining with increased substance P immunoreactivity in the supragranular plexus on that side. Met-enkephalin immunoreactivity was also increased in the outer molecular layer of the dentate gyrus on the epileptic side. Mossy fibers on the epileptic side stained more strongly with the Hicks' silver stain and with antibodies against glutamate and taurine, but less intensely with antibodies against calbindin. In the contralateral cerebellum, there was Purkinje cell loss, injury to the remaining Purkinje cells, and increased prominence of the Bergmann glia. Our observations show that prolonged unilateral seizure activity can be associated with specific histochemical changes in the human hippocampus.
 ...
PMID:Neuropathologic asymmetries in the brain of a patient with a unilateral status epilepticus. 171 86

Ten patients, suffering from drug-resistant complex partial seizures were treated for a period of up to 3 years with vigabatrin (Sabril). Vigabatrin is a novel antiepileptic agent, whose action is based on the inhibition of gamma-aminobutyric acid (GABA) aminotransferase, the enzyme responsible for the catabolism of the neurotransmitter GABA. Samples of lumbar cerebrospinal fluid were obtained from the patients prior to commencing vigabatrin therapy, and thereafter at 6 months, 1 year, 2 years, and up to 3 years following the initiation of vigabatrin treatment. The influence of vigabatrin on the cerebrospinal fluid concentrations of free and total GABA, homocarnosine, homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylethylene glycol, as well as of the drug itself, was assessed. All patients demonstrated a clinical response to vigabatrin, and the drug was well tolerated over the entire observation period. Mean (+/- SD) reduction of seizure frequency was 65% +/- 23% (range, 26% to 100%) when comparing the end of the treatment period to the previgabatrin baseline. The cerebrospinal fluid concentrations of both free and total GABA and of the dipeptide homocarnosine showed approximately 2- to 5-fold increases over baseline values, with free GABA and homocarnosine being the more sensitive variables. Cerebrospinal fluid concentrations of homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylethylene glycol were not altered in a significant manner over the observation period. These findings support the concept that the effects of vigabatrin are restricted to an effect on GABA catabolism and do not extend to the neurotransmitters dopamine and norepinephrine. Clinical efficacy and elevation of GABA and homocarnosine concentration were sustained over the period of observation.
 ...
PMID:Effect of long-term vigabatrin therapy on selected neurotransmitter concentrations in cerebrospinal fluid. 171 63


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