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)

Three calcium channel blockers were studied for efficacy in preventing seizures and death from cocaine intoxication. Rats were first pretreated with a test drug then subjected to high dose intraperitoneal cocaine. In this model, control animals developed seizures within six minutes, followed by death within ten minutes. Animals that were pretreated with diltiazem, nifedipine, or verapamil developed seizures significantly faster than controls, and at specific doses the death rate was higher than in controls for all three drugs. The potentiation of seizures and death by 2 mg/kg nifedipine pretreatment was further shown by challenge with three different doses of cocaine. This study fails to demonstrate a protective effect and suggests augmentation of cocaine toxicity by pretreatment with the three currently available calcium channel blockers. Several mechanisms by which calcium channel blockers may augment cocaine-induced toxicity are discussed.
 ...
PMID:Potentiation of cocaine toxicity with calcium channel blockers. 275 11

A young man suffering from both cluster headache and epilepsy is reported. Since the age of 37 he had recurrent generalized tonic-clonic seizures; one year later cluster headache attacks began. Neurological examination, standard laboratory tests and CT-scan were normal. The EEG showed medium-voltage sharp waves, not blocking upon eye opening, over the right parieto-temporal region. Flunarizine was added to his phenytoin therapy; it controlled both paroxysmal disorders. After six months, flunarizine was discontinued and during a one year follow-up the patient remained symptom-free. This calcium channel blocker can be regarded as an ideal drug in patients suffering from both cluster headache and epilepsy; it controls this headache syndrome and is a useful add-on to standard anti-convulsant therapy.
 ...
PMID:Cluster headache and intercalated seizures in a young man: therapeutic effectiveness of flunarizine. 275 46

Neurological complications of arterial hypertension are analyzed in 31 children (mean age = 9 years). All patients presented a renal or renovascular disease (acute nephritis + hypoplastic dysplasia , transplantation = 58%) for which malignant hypertension was the first symptom in 16%. The mean +/- SD initial blood pressure was 189 +/- 33/113 +/- 25 mm Hg and was preceded by previous symptoms in 1 patient out of 6. Neurological abnormalities consisted in seizures (48%), acute intracranial hypertension (39%), cranial palsy (23%), coma (19%), hemiplegia/paresia (16%), retinal changes (6%) or aphasia (6%). The EEG was abnormal in 50% of the patients, sometimes showing permanent paroxysmal activity. Neuroradiologic investigations revealed hemorrhagic and/or ischemic lesions in 1/5 patients. On follow-up, hypertension disappeared in 41% of the children; a decrease in renal function was noted in 56% of the patients at the last examination; neurological sequellae were present in 40% (EEG anomalies +/- epilepsy, motor deficit, retinal changes, psychomotor delay, cranial palsy) and 1 patient died. The morbidity of malignant hypertension stresses the importance of early diagnosis and treatment (calcium channel blockers) when its prevention is not possible.
 ...
PMID:[Neurologic manifestations of arterial hypertension in children]. 305 3

Flunarizine (Flu), a difluoro derivative of cinnarizine, is well known as a calcium channel blocker. Recently, many authors have reported an antiepileptic effect of this drug in experimental models of epilepsy and in the clinical use. In the present study, acute effect of Flu was examined in the amygdaloid kindled cats, and add-on effects of Flu with valproic acid (VA) was also studied. Twenty three cats were used in this study. Amygdaloid kindling was established as previously reported. A strength of stimulations for kindling was at 300 microA. Same strength was used after completion of kindling. In this "high intensity" kindling, daily stimulation invariably induced initial amygdalo-hippocampal seizures followed by secondarily generalized seizures after completion of kindling. In addition, one amygdaloid stimulation was given daily for 5 days after completion of kindling in order to make it certain to induce secondarily generalized seizures. Drugs were injected on the 6th day intraperitoneally one or two hours before the stimulation daily given for 5 days after completion of kindling (GS 6) or after 4 days clearance period of previous administration of the drug. Pretreatment with Flu (high doses: 30 or 50 mg/kg, i.p.) abolished the secondary generalization after the GS 6. With this high doses of Flu animals died of side effect within 3 days after intraperitoneal administration. With lower doses of Flu less than 3 mg/kg, i.p. of Flu no side effect was encountered but antiepileptic effect was not obtained as well. Then add-on trials of Flu were performed with valproic acid (VA). The most effective combination was 100 mg/kg, i.p. of VA with 3 mg/kg, i.p. of Flu. With this combination, secondary generalization was suppressed at a ratio of 54.5% The results confirmed antiepileptic effect of Flu and add-on effect of Flu to VA.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Acute effect of flunarizine on amygdaloid kindling in cats]. 314 81

Voltage-dependent calcium channel-blockers were studied for their ability to modulate limbic seizures induced in rats by injection of quinolinic acid and kainic acid into the hippocampus or by hippocampal kindling. Flunarizine, at 40 mg/kg (but not 20 mg/kg), reduced the total number of seizures and total time spent in seizures induced by quinolinic acid by 75%; at 60 mg/kg, both parameters were reduced more than 90%, while at 80 mg/kg seizures induced by kainic acid were not affected. Forty and 60 mg/kg of flunarizine protected hippocampal-kindled rats from fully developed convulsions (Stage 5). Nifedipine, at 20 and 40 mg/kg, was ineffective on seizures induced by both quinolinate and kainate. However, at 20 mg/kg, 57% of the kindled animals were protected from Stage 5 and total protection was achieved at 40 mg/kg. Verapamil, at 40 mg/kg, reduced by respectively, 88% and 78%, the total number of seizures and the total time spent in seizures induced by quinolinic acid, but had no effect on seizures induced by kainate and Stage 5 seizures. The results suggest that, while seizures induced by kainic acid were refractory to all voltage-dependent calcium channel blockers, binding sites affected by flunarizine and verapamil in the brain may selectively facilitate ictal activity induced by quinolinic acid. Binding sites for dihydropyridine might contribute to the increased hippocampal excitability in kindled animals. The role of calcium entry through voltage-dependent calcium channels in the occurrence of seizures in these models of limbic epilepsy is discussed.
 ...
PMID:Effect of various calcium channel blockers on three different models of limbic seizures in rats. 339 67

We previously demonstrated that the dihydropyridine calcium channel blocker, nimodipine, is an effective anticonvulsant in experimental seizures when administered parentally. Reported now are the results for the oral administration of nimodipine in pentylenetetrazole (PTZ)-induced seizures in the rabbit. Twenty rabbits were randomly assigned into 10 controls and 10 treated with nimodipine 5 mg/kg/day orally for 5 days. All animals received increasing doses of the convulsant PTZ intravenously (i.v). The epileptogenecity of this agent was assessed in all animals (mg/kg) by four electrocorticographic criteria: first seizure greater than 5 s, two seizures within 5 min, epileptiform activity for 1 h, and status epilepticus. In all four categories, nimodipine increased the seizure threshold by 50-60%. The dose of PTZ required to produce the first seizure was 27.0 +/- 5.4 mg/kg in controls and 49.6 +/- 9.9 mg/kg in treated animals (p less than 0.001). Similar values were obtained for the other three electrocorticographic categories. There were no observable adverse side effects. The results confirm our previous findings that calcium influx is critical for seizure induction, and that selective central nervous system (CNS) calcium channel blockers may emerge as a new class of anticonvulsants.
 ...
PMID:Suppression of pentylenetetrazole seizures by oral administration of a dihydropyridine Ca2+ antagonist. 362 16

Withdrawal from chronic ethanol intake results in a syndrome of tremor and hyperexcitability, which can progress to seizures and death. Drugs used therapeutically to alleviate the syndrome have sedative actions and dependence liability of their own. The basis of the syndrome is unclear, although ethanol affects many neuronal functions, including membrane calcium conductance. Calcium channel blocking drugs have been used in cardiovascular disorders; they bind to high affinity sites in the brain but have few overt actions on the central nervous system. We have tested the effects of four calcium channel antagonists on the ethanol withdrawal syndrome in rats. Nitrendipine and nimodipine abolished all spontaneous seizures and prevented or reduced seizures following an audiogenic stimulus, and mortality. Verapamil significantly decreased seizure incidence and both it and flunarizine lowered mortality. The dihydropyridines were considerably more effective than diazepam in the withdrawal syndrome but had little effect on pentylenetetrazol seizures, against which diazepam gave good protection. The calcium channel inhibitors showed no sedative activity in normal animals. The results provide evidence that alterations in calcium conductance may be involved in the ethanol withdrawal syndrome and offer possibilities for the development of non-sedative therapeutic treatment of this syndrome.
 ...
PMID:Calcium channel antagonists decrease the ethanol withdrawal syndrome. 378 69

Current research suggests that Ca2+ flux into the neuron may be a critical factor in the genesis of seizures. We report herein the influence of nimodipine, a selective central nervous system calcium channel blocker, in 60 rabbits with seizures that had been induced through ischemia, postischemia reperfusion, pentylenetetrazol, and bicuculline. In 30 animals subjected to 4 hours of ischemia, 9 of the 15 control animals had seizures in comparison with 1 of the 15 treated animals (P less than 0.005). Five animals with reperfusion seizures demonstrated similar results. In 10 animals in which a convulsant was applied topically to both cerebral hemispheres, unilateral intracarotid injection of nimodipine arrested seizures in that hemisphere alone, whereas the control contralateral hemisphere continued to have electrical seizure activity (P less than 0.001). Both placebo and verapamil were ineffective. These results suggest that Ca2+ influx is a common biochemical precipitant for various types of experimental seizures. Selective central nervous system calcium channel blockers may prove to be a new class of anticonvulsant agents.
 ...
PMID:Selective central nervous system calcium channel blockers--a new class of anticonvulsant agents. 395 Dec 56

1. The ability of two dihydropyridine calcium channel antagonists, felodipine and nitrendipine both to displace [3H]-isradipine binding in CNS tissue measured ex vivo and to protect against the ethanol withdrawal syndrome has been investigated. 2. Mice were injected with various doses of felodipine or nitrendipine and [3H]-isradipine binding measured in brain homogenates prepared 0.5, 3 or 5 h later. Inhibition versus dose curves were sigmoid and the dose required to produce 50% inhibition increased linearly with time after administration. Felodipine was approximately 10 times more potent than nitrendipine. 3. Nitrendipine (50 mg kg-1, i.p.) and felodipine (10 mg kg-1, i.p.) produced around a 75% inhibition of [3H]-isradipine binding 3 h later. Binding of [3H]-nitrendipine to cerebral tissues measured after in vivo injection of the ligand was decreased by nitrendipine (50 mg kg-1) and felodipine (10 mg kg-1) to a similar extent. 4. Nitrendipine (50 mg kg-1) prevented the behavioural signs of ethanol withdrawal as measured by handling induced convulsions, but felodipine (10 mg kg-1 or 2 mg kg-1) did not provide any protection against this effect of ethanol withdrawal. Felodipine (10 mg kg-1, twice daily) during the course of ethanol treatment also failed to attenuate the withdrawal syndrome. 5. The convulsive response to a mild audiogenic stimulus during ethanol withdrawal was increased following one dose of felodipine (5 mg kg-1, i.p.) but unaffected by nitrendipine. 6. Injection of Bay K 8644 (60 microgram, i.c.v.) produced a significant increase in handling-induced convulsive behaviour. Felodipine (10 mg kg-1, i.p.) reduced this behaviour both 60 and 120 min later, while nitrendipine (50 mg kg-1) showed a modest reduction only at 120 min.7. In contrast, nitrendipine (50mg kg-1) and felodipine (10 mg kg-1) produced similar effects on the hyperexcitability produced by handling following administration of bicuculline. Hexamethonium(8 mg kg-1) had no effect on this response.8. No change was found in [3H]-isradipine or [125I]-w-conotoxin binding to cerebral tissue prepared from ethanol-dependent mice.9. These results demonstrate that while felodipine and nitrendipine have similar actions on some CNS-mediated effects (raising seizure thresholds to several convulsant drugs), felodipine, in contrast to nitrendipine, has no effect on the ethanol withdrawal syndrome. Suggested explanations for the results include the possibility that nitrendipine may protect against the ethanol withdrawal syndrome via sites other than dihydropyridine receptors: that felodipine has partial agonist actions at dihydropyridine receptors in the CNS or that felodipine has actions which mask its protective effect in ethanol withdrawal.
 ...
PMID:The differential effects of felodipine and nitrendipine on cerebral dihydropyridine binding ex vivo and the ethanol withdrawal syndrome in mice. 752 89

In the past decade, several new antiepileptic drugs have been tested. Most recently, 5 new antiepileptic drugs have been launched onto European and US markets. These include vigabatrin, oxcarbazepine and lamotrigine in Europe, and felbamate and gabapentin in the US. In addition to these, 3 additional drugs are in the clinical investigational stage: flunarizine, fosphenytoin and stiripentol. A fourth agent is midazolam, which was originally introduced in 1986, but recently has shown effectiveness in the treatment of status epilepticus. Flunarizine is a selective calcium channel blocker that has shown anticonvulsant properties in both animal and human studies. It is a long-acting anticonvulsant that clinical studies have shown to have effects similar to those of phenytoin and carbamazepine in the treatment of partial, complex partial and generalised seizures. Fosphenytoin was developed to eliminate the poor aqueous solubility and irritant properties of intravenous phenytoin. It is rapidly converted to phenytoin after intravenous or intramuscular administration. In clinical studies, this prodrug showed minimal evidence of adverse events and no serious cardiovascular or respiratory adverse reactions. It may have a clear advantage over the present parenteral formulation of phenytoin. Midazolam is a benzodiazepine that is more potent than diazepam as a sedative, muscle relaxant and in its influence on electroencephalographic measures. It has been shown to be an effective treatment for refractory seizures in status epilepticus. Stiripentol has anticonvulsant properties as well as the ability to inhibit the cytochrome P450 system. There are significant metabolic drug interactions between stiripentol and phenytoin, carbamazepine and phenobarbital (phenobarbitone). Stiripentol has been studied in patients with partial seizures, refractory epilepsy and refractory absence seizures with some efficacious results.
 ...
PMID:New anticonvulsant drugs. Focus on flunarizine, fosphenytoin, midazolam and stiripentol. 752 21


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