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 Walker-Warburg syndrome (WWS) is an autosomal recessive disease entity within the framework of "cerebro-ocular-muscular syndromes". The gene locus is still undetected. Its diagnostic criteria have been firmly established in the literature on newborns or infants affected with the disease. However, a diagnosis of severe pathologic conditions must often be made on the basis of ultrasound examination at a fetal age. It is therefore necessary to examined whether the diagnostic criteria are sufficient to warrant a diagnosis at the fetal stage. We here report on a new family affected with WWS. Two elder siblings had presented with epileptic seizures, eye abnormalities as well as multiple skeletal dysplasias (the latter finding in the first child only) in the neonatal period, and died in their first years. Postmortem examination of the second child revealed type II lissencephaly, buphthalmos, and undifferentiated retina with rigid retinal folds. Skeletal muscle tissue was not examined. In a sibling fetus, bilateral cataract was detected in the 17th gestational week by ultrasonographic examination. Postmortem examination in the 23rd gestational week revealed type II lissencephaly and bilateral cataract. Skeletal muscle was normal. Taken together, all siblings were diagnosed as Walker-Warburg syndrome. In the fetal case, prenatal diagnosis could only be made with confidence against a background of a positive family history.
Gen Diagn Pathol 1996 May
PMID:Three siblings with Walker-Warburg Syndrome. 878 Sep 38

1. The behavioural and anticonvulsant effects of 10 1,4-benzodiazepine derivatives were studied after intraperitoneal administration in DBA/2 mice, a strain genetically susceptible to sound-induced seizures. 2. The anticonvulsant effects were evaluated on seizures evoked by means of auditory stimulation (109 dB, 12-16 kHz) in animals placed singly under a perspex dome. The rank order of potency for anticonvulsant activity was alprazolam > clonazepam > flunitrazepam > diazepam > pinazepam > desmethyldiazepam > oxazepam > prazepam > halazepam > camazepam. 3. The impairment of locomotor performance following IP administration of the above reported derivatives was also evaluated by means of the rotarod test. 4. Hypothermic activity was observed after the highest doses of the benzodiazepines studied. 5. The potency of various 1,4-benzodiazepines as inhibitors of specific [3H] flumazenil binding to membranes from cerebellum or cortex was evaluated. In general, 1,4-benzodiazepines were active as anticonvulsants at micromolar range and inhibited [3H] flumazenil binding at nanomolar range. 6. The different degree of anticonvulsant activity and impairment of coordinated motor movements cannot be directly related to the benzodiazepine binding affinity or to the lipophilicity of the compounds studied.
Gen Pharmacol 1996 Sep
PMID:1,4-Benzodiazepine derivatives as anticonvulsant agents in DBA/2 mice. 890 73

1. Phenytoin has been used with much clinical success against all types of epileptiform seizures, except petit mal epilepsy, for over 50 years. Its mechanism of action, however, is still open to interpretation. 2. Several potential targets for phenytoin action have been identified within the central nervous system. These include the Na-K-ATPase, the GABAA receptor complex, ionotropic glutamate receptors, calcium channels and sigma binding sites. 3. To date, though, the best evidence hinges on the inhibition of voltage-sensitive Na+ channels in the plasma membrane of neurons undergoing seizure activity. Quieter nerve cells are far less affected. Moreover, the fact that phenytoin also has important cardiac antiarrhythymic effects and can inhibit Na+ influx into cardiac cells supports the idea that the primary target of phenytoin is, indeed, the Na+ channel.
Gen Pharmacol 1996 Oct
PMID:Basis of the antiseizure action of phenytoin. 898 Oct 53

1. The behavioral and anticonvulsant effects of several 1, 4-benzodiazepine (BDZ) and azirino[1,2-d] [1, 4]benzodiazepine (ABDZ) derivatives were studied after intraperitoneal administration in DBA/2 mice, a strain genetically susceptible to sound-induced seizures. 2. The anticonvulsant effects were evaluated on seizures evoked by means of auditory stimulation (109 dB, 12-16 kHz) in animals placed singly under a Perspex dome. 3. The 1,4-benzodiazepines were generally more potent than the related azirino[1,2-d] [1,4]benzodiazepine derivatives which, however, showed a remarkable anticonvulsant activity. The rank order of potency for anticonvulsant activity was flunitrazepam > diazepam > pinazepam > ABDZ5 > ABDZ4 > prazepam > halazepam > ABDZ1 > ABDZ3 > camazepam > ABDZ6 > ABDZ2. 4. The impairment of locomotor performance following intraperitoneal (IP) administration of the aforementioned derivatives was also evaluated by means of rotarod test. The rank order of potency for impairment of coordinated motor movements was pinazepam > flunitrazepam > diazepam > ABDZ5 > prazepam > halazepam > ABDZ4 > ABDZ3 > ABDZ1 > camazepam > ABDZ2 = ABDZ6. 5. A hypothermic activity was observed after the highest doses of the benzodiazepines studied. 6. The potency of various 1,4-benzodiazepines and azirino[1, 2-d][1,4]benzodiazepines as inhibitors of specific [3H]flumazenil binding to membranes from cerebellum or cortex was evaluated. In general, they inhibited [3H]flumazenil binding at the micromolar range. However, some ABDZ derivatives, although active as anticonvulsants, failed to displace [3H]flumazenil. 7. The azirino[1,2-d] [1,4]benzodiazepine derivatives are more lipophilic than the related benzodiazepines, but the different degree of anticonvulsant activity and impairment of coordinated motor movements cannot be directly related to the lipophilicity of the compounds studied. 8. The pharmacologic actions of ABDZ4 and ABDZ5, which appeared as the most potent anticonvulsants of the azirino[1,2-d] [1,4]benzodiazepine derivatives, were significantly reduced by treatment with flumazenil (8.24 mumol/kg IP) suggesting a clear involvement of benzodiazepine mechanisms in the anticonvulsant activity of these compounds or their metabolites. 9. The anticonvulsant activity of ABDZ4 and ABDZ5 was also evaluated against seizures induced by the two beta-carbolines, methyl beta-carboline-3-carboxylate (beta-CCM) and methyl6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), in DBA/2 mice. Both ABDZ4 and ABDZ5 gave better protection against the seizures induced by beta-CCM than DMCM, suggesting a preferential action on BDZ1 receptors.
Gen Pharmacol 1996 Oct
PMID:Azirino[1, 2-d][1, 4]benzodiazepine derivatives and related 1,4-benzodiazepines as anticonvulsant agents in DBA/2 mice. 898 Oct 61

1. Remacemide hydrochloride has been shown to possess anticonvulsant activity in a wide range of animal models of epilepsy with ED50s in the 6-60 mg/kg range, depending on the species and route of administration. The compound also has been shown to be effective clinically as add-on therapy for partial seizures. 2. Degradation of remacemide yields the desglycinated metabolite that is approximately 2-fold more potent as an anticonvulsant agent than the parent drug. 3. Both compounds displace [3H]MK801 binding from the cerebral cortical membranes, and the metabolite is approximately 150-fold more potent in doing so than remacemide. This effect, together with the findings that the desglycinate reduces N-methyl-D-aspartate (NMDA)-induced depolarizations in a variety of preparations, suggests that the mechanism of action is through blockade of the channel site of the NMDA-receptor complex. 4. Remacemide and its metabolite, in common with other antiepileptic agents, block sustained repetitive-firing in cultured neurons. The metabolite also has been shown to decrease glutamate release from cortical slices. 5. Remacemide hydrochloride has neuroprotective properties when tested on models of cerebral ischemia. 6. The drug has low toxicity in contrast to other NMDA-channel-blocking compounds, such as MK801 and phencyclidine, probably because of its low affinity for the channel-binding site.
Gen Pharmacol 1997 Apr
PMID:Remacemide hydrochloride: a novel antiepileptic agent. 914 15

1. A putative agonist for the strychnine-sensitive glycine receptor picolinic acid was tested for its anticonvulsant activities in mice and muscle-relaxant activities in rats and compared with indole-2-carboxylic acid (I2CA), an antagonist for the strychnine-insensitive glycine receptor. Their effects on segmental reflexes in the cat spinal cord were examined to elucidate their sites of action. 2. Picolinic acid (200 and 400 mg/kg IP) delayed the onsets of strychnine- but not pentylenetetrazole-induced seizures. It delayed the onsets of bicuculline-induced seizures only at the higher dose. I2CA (200 and 400 mg/kg IP) delayed the onsets of these 3 kinds of seizures. Both compounds reduced muscle tone in rat decerebrate rigidity at a dose of 100 mg/kg IV. 3. Picolinate methylester, a picolinate derivative with higher lipophilicity, depressed spinal reflexes in both intact and spinalized cats at cumulative doses of 25 to 200 mg/kg IV. I2CA (50 mg/kg IV) inhibited spinal reflexes only in intact preparations. 4. These results suggest that the anticonvulsant and muscle-relaxant activities of picolinic acid (PA) are due to inhibition of spinal neurons, but that I2CA selectively affects supraspinal structures.
Gen Pharmacol 1997 Apr
PMID:Picolinic acid and indole-2-carboxylic acid: two types of glycinergic compounds modulate motor function differentially. 914 24

Archival material and clinical data of 10 autopsy cases of Leigh's disease (LS), aged from 44 days to 9 years at death, were reviewed. Development delay, irregular respiration, feeding difficulty, and abnormal eye signs were the most common symptoms. Seizures (five of ten cases) were also frequent. In most patients, the diagnosis of LS was established postmortemly by the presence of symmetrical spongiform lesions affecting several brain centers at autopsy. The histologic examination disclosed associated hypertrophic cardiomyopathy in six cases, while fatty infiltration of the hepatocytes was observed in four cases. Microvesicular degeneration of the renal tubular epithelial cells was also seen in four cases. Our observations suggest that liver and kidney involvement is a component of LS and that this rare entity has to be considered as a polysystematic disorder, able to affect other organs besides the nervous system and the heart, a fact which has not been emphasized enough in the existing literature.
Gen Diagn Pathol 1997 Jun
PMID:Subacute necrotizing encephalomyelopathy (Leigh's disease): a clinicopathologic study of ten cases. 922 57

1. Contribution of nitric oxide to the convulsive seizures induced by fluoroquinolones (FQs) coadministered with 4-biphenyl acetic acid (BPAA), the active metabolite of fenbufen, was assessed in mice. 2. Enoxacin + 4-biphenyl acetic acid caused clonic seizures in all treated mice, followed by tonic seizures and death. These events were associated with a significant increase in intracerebellar cyclic GMP. 3. Pretreatment with the nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methylester (L-NAME), but not with D-NAME, significantly reduced the incidence of convulsions and lethality, as well as the increase in cyclic GMP. 4. Pretreatment with N-methyl-D-aspartic acid (NMDA)-receptor antagonist, MK-801, inhibited only the transition of clonic seizure to tonic seizure without affecting the incidence of clonic seizure and lethality. 5. These findings suggest that FQs + BPAA exert convulsions by activating NOS partly through the mediation of the NMDA receptor in the brain cells.
Gen Pharmacol 1997 Nov
PMID:Role of nitric oxide in the convulsive seizures induced by fluoroquinolones coadministered with 4-biphenyl acetic acid. 934 23

1. Glutamate seems to play a central role in epilepsy, and kindling is considered the most useful experimental model in revealing plastic changes associated with epileptic features. 2. The aim of this study was to optimize pentylenetetrazol (PTZ)-kindling conditions in mice and analyze glutamatergic changes associated with this phenomena. 3. A significant increase (85.7%) in seizuring animals was observed after four PTZ administrations, with all subjects presenting full seizures after five administrations. 4. PTZ kindling, but not acute seizure, significantly increased (169.8%) the specific binding of [3H]glutamate in the cerebral cortex. 5. The development of PTZ-induced kindling in mice was prevented by the coadministration of phenobarbital or diazepam. 6. This study indicates that mice can be used in a reliable model of PTZ-induced kindling and that, as in rats, the kindling increases the specific [3H]glutamate binding in the cerebral cortex, therefore allowing for screening new drugs that can interfere in the plastic changes believed to underlie epileptic phenomena.
Gen Pharmacol 1998 Jul
PMID:A neuropharmacological analysis of PTZ-induced kindling in mice. 959 77

1. The aim of this study was to investigate the possible anticonvulsant effect of a dihydropyridine calcium antagonist, isradipine, which easily crosses the blood-brain barrier displaying high affinity and specificity for the brain L-type voltage-sensitive calcium channel, on maximal electroshock seizures in mice. 2. Isradipine at i.p. doses of 2.5 mg/kg and 5.0 mg/kg was found to cause a statistically significant increase in the convulsion threshold of maximal electroshock seizures in a dose-dependent manner (P = 0.047 and P = 0.022, respectively). 3. It was concluded that the mode of action of the anticonvulsant effect of isradipine is related to blockade of the intraneuronal calcium currents, which play an important role in epileptic activity.
Gen Pharmacol 1998 Jul
PMID:The effect of isradipine on maximal electroshock seizures in mice. 959 91


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