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)

A role for ionotropic (NMDA, AMPA, and kainate) excitatory amino acid (EAA) receptors in seizure and seizure-related brain damage is well documented. To study the possible role of metabotropic (G-protein linked) EAA receptors in this regard, a highly selective metabotropic EAA agonist was injected into the hippocampus of halothane-anesthetized rats. This resulted in delayed-onset seizures and selective hippocampal neuronal damage that was indirectly mediated by NMDA receptors. This provides direct evidence for a novel role of metabotropic EAA receptors in the etiology of seizures and neuronal damage.
 ...
PMID:Activation of hippocampal metabotropic excitatory amino acid receptors leads to seizures and neuronal damage. 140 85

The action of MK-801 (NMDA antagonist; 0.1 and 0.5 mg/kg, IP) was tested against picrotoxin-induced seizures (3-6 mg/kg, IP) in rats aged 7, 12, 18, 25, and 90 days. We found MK-801 only inconsistently affected clonic seizures in 12- and 25-day-old rats, whereas tonic-clonic seizures were suppressed or delayed in almost all age groups. In addition, the lethality of picrotoxin was diminished by the higher dose of MK-801 in all age groups. The results suggest: a) different generators for both seizure patterns (clonic and tonic-clonic), b) an involvement of NMDA receptors in the genesis of tonic-clonic seizure pattern, and c) an interaction of MK-801 with GABAergic transmission throughout the entire development studied.
 ...
PMID:Picrotoxin-induced tonic-clonic seizures and lethality are decreased by MK-801 in developing rats. 140 14

Early Pb exposure is known to disrupt the development of the hippocampus and result in deficits in learning and memory capacities and altered seizure susceptibility. The excitatory amino acid, NMDA, is found in high concentrations in the hippocampus and has been implicated in learning and memory functions and seizure activity. Rat pups nursed mothers exposed to high (4%), moderate (0.4%), or low (0.05%) levels of PbCO3 in their diet, or a Na2CO3 control diet from postnatal day 1 (P1) to P25. Rat pups were injected with varying doses of NMDA on P15 or P25. Control animals showed a characteristic slowly developing response to NMDA, usually including tail twitches and wet dog shakes at approximately 10 and 40 mg/kg at P15 and P25, respectively, with status epilepticus and death occurring at 40 and 80 mg/kg. Lead-exposed animals displayed an altered sensitivity to NMDA, with high and medium Pb animals showing the onset of behavioral signs and death at lower NMDA doses, the degree of which being dependent on the level of Pb exposure. Low Pb-exposed animals showed a more variable and attenuated response to NMDA. The data are discussed in terms of the possible mechanisms of Pb neurotoxicity.
 ...
PMID:Altered sensitivity to NMDA following developmental lead exposure in rats. 140 40

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

Milacemide, an acylated prodrug of glycine, was able to increase the efficacy with which [+]-5-methyl-10,11-dihydro-5h-dibenzo[a,d]cyclohepten-5,10-imine meleate (MK 801) antagonized the electrical precipitation of seizures in mice. The mechanism of milacemide's potentiation of MK 801's antiseizure efficacy in intact mice is unclear; however, a glycine agonist selective for the strychnine-insensitive site on the NMDA receptor complex was also able to potentiate MK 801. The exciting possibility exists that an exogenous glycinergic intervention can potentiate NMDA-mediated neural transmission in intact animals.
 ...
PMID:Glycinergic interventions potentiate the ability of MK 801 to raise the threshold voltage for tonic hindlimb extension in mice. 143 97

This study assessed the behavioral and electrographic effects of (+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5,10-imine maleate (MK-801) (0.1 and 0.5 mg/kg, IP), a noncompetitive antagonist of the NMDA receptors, in hippocampal (HIP)-kindled cats. MK-801 at a higher dose significantly reduced the afterdischarge duration, but not the behavioral seizure stage, of HIP-kindled seizures. This anticonvulsant effect occurred in association with the appearance of severe behavioral toxicity and paradoxical worsening of background electroencephalogram characterized by profound spike and wave discharges. The present data suggest the dissociative effect of MK-801 on seizure activity and limitations of its clinical utility as an antiepileptic agent.
 ...
PMID:The NMDA receptor antagonist MK-801 has a dissociative effect on seizure activity of hippocampal-kindled cats. 147 11

The behavioural and neuropathological effects of both systemic and intrahippocampal injections of paraquat dichloride (1,1'-dimethyl 4,4'-bipyridinium dichloride) were studied in rats. Paraquat (0.1-1.0 mumol) injected into the dorsal hippocampus, produced limbic motor seizures within a few minutes of injection followed by neuronal damage in the CA1 and CA3 pyramidal cell layers, pyriform cortex, dentate granule cell layer and in the hilus fascia dentata at 24 hr (n = 9 rats). A smaller dose of paraquat (10 nmol) was ineffective. The effects of intrahippocampal injections of paraquat (1 mumol) were prevented by administering it together with atropine (50 nmol; n = 6 rats) or by giving it 60 min. after MK 801 (0.3 mg.kg-1 intraperitoneally). Systemic injections of paraquat (20-100 mg.kg-1) also produced forelimb clonus and rearing in 10 out of 15 animals. Neuronal cell death was found 24 hr later in 9 of these rats and was restricted to the pyriform cortex, the brain region with the highest concentrations of paraquat. Atropine (150 mg.kg-1 intraperitoneally given 60 min. previously) completely prevented the motor seizures but cell death still occurred in 2 of the 6 animals tested. In conclusion, both systemic and intrahippocampal injections of paraquat produced behavioural excitation accompanied 24 hr later by brain damage and antagonist studies suggested involvement of muscarinic and NMDA receptors in the neurotoxic mechanism.
 ...
PMID:Production of limbic motor seizures and brain damage by systemic and intracerebral injections of paraquat in rats. 148 May 53

We assessed the acute effect of MK-801 (0.05-0.7 mg/kg), a noncompetitive NMDA-receptor antagonist, on hippocampus-kindled seizures induced with low-frequency (2 Hz) electrical stimulations. MK-801 dose-dependently increased the seizure threshold (PNT, the number of stimulating pulses required for the triggering of epileptic after discharge), whereas most of the previous studies which assessed the effect of MK-801 on kindled seizures could not detect the elevation of seizure threshold by MK-801. In addition MK-801 decreased the severity of induced seizures at low doses at which previous studies could not detect the antiepileptic effect of MK-801, suggesting that the low-frequency kindling technique might be a more sensitive and reliable model of epilepsy than the conventional high-frequency kindling technique.
 ...
PMID:Antiepileptic effects of MK-801, a noncompetitive NMDA-receptor antagonist, in the low-frequency kindling model of epilepsy. 148 58

The anticonvulsant effect of 1-naphthylacetyl spermine, an analogue of Joro spider toxin (JSTX), was studied against seizures induced by quisqualate (QUIS), a non-NMDA agonist, as assessed electrophysiologically and behaviorally in freely moving rats. Electrodes were implanted into right dorsal hippocampus and an injection cannula for drugs into right ventricle. The pretreatment with JSTX analogue significantly inhibited both of QUIS-induced hippocampal discharges (80-11%) and generalized tonic clonic seizures (100-33%) in a dose-dependent manner, whereas JSTX had no effect on seizures induced by quinolinate, a NMDA agonist. The paper provides the first direct evidence that the JSTX analogue exerts a potent and selective suppression of hippocampal epileptic discharges mediated by non-N-methyl-D-aspartate (non-NMDA) receptors.
 ...
PMID:An analogue of Joro spider toxin selectively suppresses hippocampal epileptic discharges induced by quisqualate. 149 67

Various anticonvulsant drugs were evaluated for their ability to protect against clonic seizures induced in mice by intraventricular injection of the K+ channel blocking peptide dendrotoxin (DTX). Phenytoin, the phenytoin-like anticonvulsant carbamazepine and the broad spectrum drug valproate were effective in this model, whereas the GABA-enhancers diazepam and tiagabine, the NMDA antagonists (+/-)-CPP and (+)-MK-801, the AMPA antagonist NBQX, the antiabsence drug ethosuximide and the Ca2+ channel antagonist nimodipine were inactive. In contrast to the lack of activity of other NMDA antagonists, phencyclidine and ADCI [(+/-)-aminocarbonyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine] were potent antagonists of DTX-induced seizures.
 ...
PMID:Protection against dendrotoxin-induced clonic seizures in mice by anticonvulsant drugs. 150 73


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