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

The neurological mutant mouse strain E1 is a model for complex partial seizures in humans. The inheritance of epileptic seizures with seven conventional chromosomal markers and over 60 endogenous proviral markers was studied by means of back-crosses of E1 with two seizure-resistant strains, DBA/2J and ABP/LeJ. The major gene responsible for this epileptic phenotype (El-1) was localized to a region distal with respect to the centromere on chromosome 9. At least one other gene, El-2, linked to proviral markers on chromosome 2, also influences the seizure phenotype. In addition, a potential modifier of seizures was detected in the DBA/2J background. The location of El-1 on distal chromosome 9 may allow identification of an epilepsy candidate gene in humans on the basis of conserved synteny with human chromosome 3.
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PMID:Genes for epilepsy mapped in the mouse. 187 1

The waking EEG of DBA/2 mice is punctuated by conspicuous bursts of high-amplitude, 6-7-cps spindles. Catecholamine depletion by 2.0 mg/kg, i.p., reserpine or 120 mg/kg, i.p., alpha-methyl-p-tyrosine increased the occurrence and duration of these brief spindle episodes (BSEs). This effect may reflect noradrenergic depletion because the beta-noradrenergic antagonist propranolol (10 mg/kg, i.p.) powerfully promoted BSE occurrence and increased BSE duration in freely-moving and midpontine-transected mice, whereas the dopamine antagonist haloperidol (2.0 mg/kg, i.p.) neither increased nor decreased BSE occurrence. The alpha-noradrenergic agonist clonidine (0.05 mg/kg, i.p.), which is known to inhibit noradrenergic neuronal firing as well as act at postsynaptic alpha receptors, also promoted BSE occurrence in transected mice. In addition, the dopamine agonist apomorphine (2.0 mg/kg, i.p.) increased BSE occurrence in freely-moving mice once the behavioral activation it produced subsided. These effects were blocked by 2.0 mg/kg haloperidol, i.p. The convulsant drug pentylenetetrazol, which is known to promote BSE occurrence at subconvulsant doses in DBA/2 mice, may activate BSEs, in part, by activating dopamine neurons: 2.0 mg/kg haloperidol, i.p., partially blocked the facilitation of BSEs by 20 mg/kg pentylenetetrazol, i.p., in midpontine DBA/2 mice. Thus, noradrenergic neurons may block spindle occurrence in DBA/2 mice whereas dopamine neurons may be one of several systems that can promote spindle occurrence.
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PMID:Catecholamine regulation of neocortical spindling in DBA/2 mice. 299 88

C57BL/6 inbred mice lack the 1-5 sec bursts of 6-7 cps spindles characteristic of the neocortical EEG of DBA/2 mice during waking. C57BL/6 mice (1) may be unable to generate any synchronized cortical EEG activity, (2) may lack the thalamocortical circuitry required to generate these brief spindle episodes (BSEs), (3) may lack mechanisms that can activate this circuitry or (4) may possess a potent mechanism to suppress BSE initiation and generation. Possibilities 1 and 2 have been eliminated because C57BL/6 mice generate pentobarbital, rostropontine-induced and sleep spindles, and because certain C57BL/6 sleep spindles resembled the BSEs seen in DBA/2 mice. Possibilities 3 and 4 were examined in the experiments reported here. In DBA/2 mice, pentylenetetrazol activates BSEs at subconvulsant doses. In contrast, neither 20 nor 50 mg/kg, IP, pentylenetetrazol activated BSEs in C57BL/6 mice, although the higher dose provoked 4-5 cps slow waves and myoclonic jerks. In DBA/2 mice, the beta-noradrenergic antagonist propranolol has been reported to powerfully release BSEs. In C57BL/6 mice, 10 and 15 mg/kg propanolol weakly released BSEs; fewer than 3 per hour occurred. Hence neither possibilities 3 and 4 are sufficient in themselves to explain the lack of BSEs during waking in C57BL/6 mice. However, simultaneous administration of 10 mg/kg propranolol and 20 mg/kg pentylenetetrazol provoked numerous BSEs in C57BL/6 mice. This suggests that perhaps C57BL/6 mice, as compared to DBA/2 mice, possess both a more powerful noradrenergic mechanism to suppress spindles and a more weakly functioning mechanism to activate BSEs. Hence possibilities 3 and 4 may both be correct.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neural mechanisms distinguishing the neocortical EEG of C57BL/6 mice from that of DBA/2 mice. 399 62

Continuous twenty-four hour EEG recordings were conducted on freely-moving DBA/2 and C57BL/6 inbred mice. No brief spindle episodes (BSEs: 6-7 cps, 1-5 sec duration, high amplitude spindle bursts) were seen in the waking EEG of C57BL/6 mice. BSEs were a conspicuous element of the EEG during active waking (AW) and quiet waking (QW) in DBA/2 mice. BSEs occurred at a 10X faster rate in QW than in AW and had a longer duration. Sleep spindle bursts resembling BSEs were seen in both C57BL/6 and DBA/2 mice, and occasionally were observed to follow a K-complex. Rostropontine, but not midpontine, brainstem transection released spindles in both strains. Pentobarbital produced spindles in both strains. The waveforms of the waves comprising BSEs, sleep spindles, transection-induced spindles and barbiturate spindles were quite similar, though differing in frequencies and amplitude. Genetic factors may be critical for the lack of BSEs during AW and QW in C57BL/6 mice and for the occurrence of BSEs during AW in DBA/2 mice. In contrast, most other rodents whow a third pattern: BSEs only during QW. Since C57BL/6 mice can generate spindles under some circumstances, the absence of spindles during waking reflects some alteration in the mechanisms that control the initiation of BSEs rather than a lack of the circuits required to generate a BSE. These mechanisms are distinct from those processes of arousal that produce the background EEG desynchronization of waking. Following both rostropontine and midpontine transection, the background EEG is desynchronized, yet after rostropontine, but not midpontine transection, BSEs occur freely, at a rate over 200 per hour.
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PMID:Characterization of cortical spindles in DBA/2 and C57BL/6 inbred mice. 644 15

For a long time it has been suspected that epilepsy and cardiac arrhythmia may have common molecular background. Furthermore, seizures can affect function of the central autonomic control centers leading to short- and long-term alterations of cardiac rhythm. Sudden unexpected death in epilepsy (SUDEP) has most likely a cardiac mechanism. Common elements of pathogenesis create a basis for the assumption that antiarrhythmic drugs (AADs) may affect seizure phenomena and interact with antiepileptic drugs (AEDs). Numerous studies have demonstrated anticonvulsant effects of AADs. Among class I AADs (sodium channel blockers), phenytoin is an established antiepileptic drug. Propafenone exerted low anti-electroshock activity in rats. Lidocaine and mexiletine showed the anticonvulsant activity not only in animal models, but also in patients with partial seizures. Among beta-blockers (class II AADs), propranolol was anticonvulsant in models for generalized tonic-clonic and complex partial seizures, but not for myoclonic convulsions. Metoprolol and pindolol antagonized tonic-clonic seizures in DBA/2 mice. Timolol reversed the epileptiform activity of pentylenetetrazol (PTZ) in the brain. Furthermore, amiodarone, the representative of class III AADs, inhibited PTZ- and caffeine-induced convulsions in mice. In the group of class IV AADs, verapamil protected mice against PTZ-induced seizures and inhibited epileptogenesis in amygdala-kindled rats. Verapamil and diltiazem showed moderate anticonvulsant activity in genetically epilepsy prone rats. Additionally, numerous AADs potentiated the anticonvulsant action of AEDs in both experimental and clinical conditions. It should be mentioned, however, that many AADs showed proconvulsant effects in overdose. Moreover, intravenous esmolol and intra-arterial verapamil induced seizures even at therapeutic dose ranges.
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PMID:Antiarrhythmic drugs and epilepsy. 2494 53