Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0149958 (complex partial seizures)
 2,563 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pilocarpine (PILO) induces in rats limbic seizures that become secondarily generalized and evolve to status epilepticus (SE). Spontaneous recurrent seizures are registered during the long-term period following the systemic administration of PILO in rats. EEG, behavioral, and pathological features resemble those of complex partial seizures. The antiepileptic drugs (AEDs) diazepam, phenobarbital (PB), valproic acid (VPA) and trimethadione protect against PILO-induced SE while phenytoin (PHT) and carbamazepine (CBZ) are ineffective. Studies with AEDs on spontaneous seizures (chronic period) of this model have not yet been established. We now report the effects of different AEDs on spontaneous seizures. Male Wistar rats were subjected to PILO-induced SE. Following recovery from SE animals were daily observed in order to detect spontaneous seizures and to establish the baseline seizure frequency. PB 40 mg/kg, PHT 100 mg/kg, CBZ 120 mg/kg, VPA (450 mg/kg and 600 mg/kg) and ethosuximide (ETX) 400 mg/kg were given daily to epileptic rats for two weeks during the spontaneous recurrent seizures period. PB, CBZ and PHT were effective against spontaneous seizures. VPA was also effective against spontaneous seizures at the dose of 600 mg/kg and ETX was inactive against these seizures. Such pharmacological profiles correlate well with complex partial seizures. The results indicate that spontaneous recurrent seizures after PILO-induced SE may be a useful model for finding new AEDs with better efficacy against complex partial seizures. The use of animal models that share both pharmacological and phenomenological features with human epilepsy might improve their predictive value for specific types of human epilepsy.
 ...
PMID:Effects of conventional antiepileptic drugs in a model of spontaneous recurrent seizures in rats. 775 May 14

1. Pilocarpine administration has been used as an animal model for temporal lobe epilepsy since it produces several morphological and synaptic features in common with human complex partial seizures. Little is known about changes in extracellular neurotransmitter concentrations during the seizures provoked by pilocarpine, a non-selective muscarinic agonist. 2. Focally evoked pilocarpine-induced seizures in freely moving rats were provoked by intrahippocampal pilocarpine (10 mM for 40 min at a flow rate of 2 microl min(-1)) administration via a microdialysis probe. Concomitant changes in extracellular hippocampal glutamate, gamma-aminobutyric acid (GABA) and dopamine levels were monitored and simultaneous electrocorticography was performed. The animal model was characterized by intrahippocampal perfusion with the muscarinic receptor antagonist atropine (20 mM), the sodium channel blocker tetrodotoxin (1 microM) and the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (dizocilpine maleate, 100 microM). The effectiveness of locally (600 microM) or systemically (10 mg kg(-1) day(-1)) applied lamotrigine against the pilocarpine-induced convulsions was evaluated. 3. Pilocarpine initially decreased extracellular hippocampal glutamate and GABA levels. During the subsequent pilocarpine-induced limbic convulsions extracellular glutamate, GABA and dopamine concentrations in hippocampus were significantly increased. Atropine blocked all changes in extracellular transmitter levels during and after co-administration of pilocarpine. All pilocarpine-induced increases were completely prevented by simultaneous tetrodotoxin perfusion. Intrahippocampal administration of MK-801 and lamotrigine resulted in an elevation of hippocampal dopamine levels and protected the rats from the pilocarpine-induced seizures. Pilocarpine-induced convulsions developed in the rats which received lamotrigine perorally. 4. Pilocarpine-induced seizures are initiated via muscarinic receptors and further mediated via NMDA receptors. Sustained increases in extracellular glutamate levels after pilocarpine perfusion are related to the limbic seizures. These are arguments in favour of earlier described NMDA receptor-mediated excitotoxicity. Hippocampal dopamine release may be functionally important in epileptogenesis and may participate in the anticonvulsant effects of MK-801 and lamotrigine. The pilocarpine-stimulated hippocampal GABA, glutamate and dopamine levels reflect neuronal vesicular release.
 ...
PMID:NMDA receptor-mediated pilocarpine-induced seizures: characterization in freely moving rats by microdialysis. 924 54