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 mechanisms of petit mal epilepsy remain a mystery despite successful therapy. Previous workers have proposed that paroxysmal activity of cortical inhibitory systems plays a role in absence seizures. In this study, we have compared the effects of bicuculline, a potent convulsive agent and GABA antagonist, with ethosuximide, a drug used to treat petit mal epilepsy, on the thalamocortical motor system of the cat. Under chloralose anesthesia, sequential pairs of pulses were delivered to ventrolateral thalamus (VL) varying either pulse amplitude or interval. The evoked responses were recorded from sensorimotor cortex, analyzed on-line by computer, and plotted as an excitability curve (mean response amplitude as a function of pulse interval), or a family of threshold curves (mean response amplitude as a function of stimulus amplitude at various fixed intervals). Administration of each drug resulted in increased thalamocortical excitability and decreased threshold to stimulation for short pulse-pair intervals, with diminished duration of the excitability curve. Increased alertness was produced by both drugs. Studies with grand mal anticonvulsants demonstrated entirely different effects. Because GABA is thought to be the primary inhibitory transmitter in VL and cerebral cortex, bicuculline would be expected to result in disinhibition. The similarity of the data for ethosuximide suggests that ethosuximide also suppresses inhibition in the thalamocortical motor system and adds further to the accumulating evidence of the role of inhibitory system in petit mal epilepsy.
 ...
PMID:Ethosuximide and bicuculline inhibition in petit mal epilepsy. 9 76

Microinjection of drugs, such as muscimol, into the substantia nigra pars reticulata (SNpr) can inhibit several types of experimental seizures. Some findings suggested that this was a result of disinhibition of neurons receiving input from GABAergic nigrotectal cells. Indeed, it was reported that bicuculline methiodide (BMI), infused into the tectal region that was reported to receive nigral input, produced an anticonvulsant effect against maximal electroshock (MES) convulsion. Since previous work had suggested that the anticonvulsant effect of intranigral muscimol depended on the particular experimental seizure used, three different experimental seizures were used in the present study to evaluate the effects of BMI infusion into the tectum. Guide cannulas aimed at the tectal region receiving nigral innervation were stereotaxically implanted in rats a week before testing. Bilateral intratectal infusions of BMI (25 ng/side) had an anticonvulsant effect against MES convulsions, confirming a previous report. In contrast, the same BMI pretreatment worsened convulsions produced by either systemic pentylenetetrazol (40 mg/kg, i.p.) or bicuculline (0.5 mg/kg, i.v.). The effects of intratectal BMI were seizure model-dependent, suggesting different functional interconnections between tectum and those pathways responsible for generalization of MES as compared to PTZ or bicuculline convulsions.
 ...
PMID:Infusion of bicuculline methiodide into the tectum: model specificity of pro- and anticonvulsant actions. 152 25

Appearances of pentetrazole-, picrotoxin- and strychnine-induced convulsive seizures in taurine-deficient mice produced by treatment with guanidinoethyl sulfonate (GES), a taurine transport antagonist, were investigated. Mice were fed a taurine-free diet and water containing 1% GES from 2 weeks of pregnancy to weaning. The same feeding condition was applied to male offsprings from 3 weeks of age. At 5 weeks of age, convulsants were administered to some mice and the others were sacrificed for determination of brain amino acids concentrations. The incidences of both seizure and death for strychnine and death for picrotoxin were enhanced by treatment with GES, whereas the latency of pentetrazole-induced tonic extensor was prolonged. Significant decrease of brain taurine, asparaginic acid and GABA concentrations were observed in mice treated with GES. These results suggest that convulsive seizures caused by disinhibition of taurine and GABA system are enhanced by deficiency of brain taurine level.
 ...
PMID:[Drug-induced seizures in taurine-deficient mice]. 179 96

Activation of GABAergic transmission within the substantia nigra has been shown to suppress several forms of generalized seizures in experimental models of epilepsy. More especially, such pharmacological manipulations suppress spontaneous and chemically-induced generalized non-convulsive seizures in the rat. The aim of the present study was to examine the role of the dopaminergic and GABAergic thalamic and collicular nigral outputs in this antiepileptic effect. For this purpose, we examined the effects of output destruction on the antiepileptic effect of intranigral injections of a GABA agonist or pharmacological blockade of the neurotransmission at the nerve terminal level in rats with spontaneous absence seizures. After selective destruction of dopaminergic neurons within the substantia nigra with 6-hydroxydopamine (5 micrograms/side) or hemisection of the ascending nigral output, bilateral intranigral injection of muscimol (2 ng/side) still significantly suppressed generalized non-convulsive seizures. Bilateral lesioning of the ventromedial nucleus of the thalamus did not abolish the antiepileptic effects of intranigral muscimol (2 ng/side) and the GABA antagonist, picrotoxin, when given into this thalamic nucleus (10 ng/side) also failed to induce suppression of spike and wave discharges. The antiepileptic effects of intranigral injection of muscimol (2 ng/side) was reversed by bilateral electrolytic lesions of the superior colliculus. Blockade of the GABAergic transmission at this level with picrotoxin (40 ng/side) significantly suppressed generalized non-convulsive seizures. Finally, excitation of collicular cell bodies with low doses of kainic acid (4 and 8 ng/side) also resulted in a suppression of spike and wave discharges. These results demonstrate that the GABAergic nigrocollicular pathway is critical for the inhibitory control of the substantia nigra over generalized non-convulsive seizures. The data further suggest that antiepileptic effects observed following potentiation of GABAergic transmission in the substantia nigra result from a disinhibition of collicular cell bodies.
 ...
PMID:Involvement of the nigral output pathways in the inhibitory control of the substantia nigra over generalized non-convulsive seizures in the rat. 212 73

5 alpha-Pregnan-3 alpha-ol-20-one (3 alpha-OH-DHP) blocked seizures induced by nicotine (4 mg/kg, i.p.) in C3H male mice with an ID50 of 2.37 +/- 0.66 mg/kg (average +/- 95% confidence limit). This steroid (1 microM) also increased paired-pulse inhibition in the hippocampus approximately 40% after 50 min exposure; nicotine (200 microM) partially reversed this effect. Since nicotine and 3 alpha-OH-DHP may have opposite effects on endogenous inhibitory systems, it is proposed that nicotine-induced seizures may involve a disinhibitory mechanism and that 3 alpha-OH-DHP protects against seizures by preventing disinhibition.
 ...
PMID:5 alpha-Pregnan-3 alpha-ol-20-one blocks nicotine-induced seizures and enhances paired-pulse inhibition. 225 97

Two cases of electroconvulsive therapy (ECT) in adolescence are presented and the literature on the use of ECT in childhood and adolescence is reviewed. ECT was effective in children and adolescents with bipolar disorder and depression. Inadequate information exists to make a judgment regarding schizophrenia, delirium, and anorexia nervosa. ECT is not effective in autism and chronic organic brain syndromes. Complications cited include organicity and seizures in the period immediately after ECT, anxiety reactions, and disinhibition. Long-term memory deficit or cognitive impairment has not been found, although further research to rule out residual impairment is needed.
 ...
PMID:A review of ECT for children and adolescents. 222 48

Anticonvulsant activity in a wide variety of experimental seizure models can be obtained by enhancing gamma-aminobutyric acid (GABA) transmission within the pars reticulata of substantia nigra. Recent evidence indicates that the nigrotectal projection may mediate some of the nigra-evoked anticonvulsant effects. The action of GABA within substantia nigra would, by inhibiting the GABAergic nigrotectal projections, cause disinhibition of target neurons in the superior colliculus. This hypothesis predicts that administration of GABA antagonists into the region of the superior colliculus that receives nigrotectal terminals should also have anticonvulsant actions. We therefore examined the effects of injections of bicuculline methiodide aimed at rostrolateral superior colliculus upon maximal electroshock convulsions. The incidence and duration of tonic hindlimb extension was substantially reduced by these injections, a result consistent with the hypothesis that the nigrotectal GABAergic pathway may mediate the anticonvulsant actions of GABA transmission in the substantia nigra.
 ...
PMID:Anticonvulsant action of GABA receptor blockade in the nigrotectal target region. 253 35

Bath application of muscimol (10-20 microM) to hippocampal slices obtained from rats on postnatal days 10-15 produced epileptiform activity in the form of multiple population spikes in 20% of slices tested, concurrent with marked disinhibition. The disinhibition occurred in nearly 100% of cases tested at muscimol concentrations that produced epileptiform activity. Paired pulse analysis of GABAergic recurrent inhibition revealed a muscimol-induced disinhibitory effect involving a decrease in maximum possible inhibition. Spontaneous and antidromically elicited inhibitory postsynaptic potentials (IPSPs) recorded intracellularly were suppressed by muscimol. Current-voltage analysis of the recurrent IPSPs suggests that muscimol acted at a number of sites to produce disinhibition. The input conductance of the postsynaptic pyramidal cell increased due to muscimol, creating a current shunt which likely decreased the efficacy of synaptic currents. Muscimol also caused a decrease in the conductance due to the IPSP as well as a shift in the depolarizing direction of the equilibrium potential of the IPSP. The data indicate that muscimol, a GABAA agonist, can produce disinhibition resulting from the multiple consequences of its action. We conclude that the physiologic consequences of GABAA agonist treatment are complex. On the other hand, neurons are likely to be inhibited by a tonic increase in membrane conductance. However, since recurrent inhibition is simultaneously compromised, excitatory vollies of sufficient intensity may overcome the tonic inhibition and produce a hyperexcitable state. In some cases, this disinhibition may induce epileptiform activity. These observations are relevant in light of the proposed use of GABA agonists clinically to control seizures.
 ...
PMID:Disinhibitory actions of the GABAA agonist muscimol in immature hippocampus. 255 27

Female mice form a long-term olfactory memory to the pheromones of the male that mates with them. This memory is dependent on neural mechanisms within the accessory olfactory bulb. In this study we show that localized infusions of the excitatory amino acid receptor blocker, gamma-D-glutamylglycine, into the accessory olfactory bulb prevents memory formation. This is in marked contrast to the effects of infusions of the specific N-methyl-D-aspartate receptor antagonists, D-2-amino-5-phosphonovaleric acid and MK 801, which are without effect on memory formation. Excitatory amino acid receptor blockade by localized infusion of these drugs into the accessory olfactory bulb induced seizures. This paradoxical effect could only be due to disinhibition of granule cell GABAergic inhibitory feedback to the mitral cell. This was confirmed by the pregnancy blocking effect of these drugs, an event which also occurs with bicuculline infusions into the accessory olfactory bulb. These findings strongly implicate excitatory amino acid receptors in memory formation to the pheromones of the mating male and localize the mechanism to the reciprocal dendro-dendritic synapse between mitral and granule cells.
 ...
PMID:Impairment of olfactory memory by local infusions of non-selective excitatory amino acid receptor antagonists into the accessory olfactory bulb. 256 19

Ca2+-free solutions evoke spontaneous epileptiform activity in area CA1 of hippocampal slices from adult and young rats at the age of 7/8, 14/15 and 23/24 days. Studies with combined Ca2+-selective and K+-selective microelectrodes showed that this epileptiform activity commenced at higher Ca2+ levels in young than in adult animals. Unlike in disinhibition seizures, [K+]o did not rise to abnormally high levels. We further found that Ca2+ washout curves from young animals were much faster than those from adult slices, suggesting that the extracellular space is wider in young animals than in adult ones.
 ...
PMID:Low calcium-induced epileptiform activity in hippocampal slices from infant rats. 277 1


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