Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amantadine HCl was given to 10 children with medically refractory seizures; other anticonvulsant medications were continued unchanged through the 12- to 16-week trial. Several patients noted improvement in control of myoclonic or atypical absence seizures. Tonic seizures were controlled in one patient, but worsened in another. Tonic-clonic and atonic seizures remained unchanged or worsened. Amantadine may be useful as an adjunctive anticonvulsant in some children with refractory atypical absence or myoclonic seizures.
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PMID:Amantadine in the treatment of refractory epilepsy in childhood: an open trial in 10 patients. 392 May 49

The pro- and anticonvulsant effects of phencyclidine (1-[1-phenylcyclohexyl]piperidine HCl, PCP), a number of its analogues, and SKF 10047 were investigated in rats. The PCP analogues were compounds produced by substitutions for the phenyl and piperidine rings of PCP and were selected to elucidate the structure-activity relationships existing between PCP and its pro- and/or anticonvulsant effects. All of the compounds, except ketamine, induced convulsions at high (12.8-25.6 mg/kg, i.v.), yet almost always sublethal doses. Ketamine failed to induce convulsions, even at lethal doses (51.2 mg/kg, i.v.). The acute pro- or anticonvulsant actions of PCP were then investigated. Rats were subjected to transorbital electroconvulsive shock subsequent to i.p. injections of saline or 0.625, 2.5, 5.0, 10.0 or 20.0 mg/kg PCP. It was found that PCP induced an acute, dose-dependent anticonvulsant effect. The acute pro- and/or anticonvulsant actions of the remaining compounds were then investigated by administration of electroconvulsive shock subsequent to i.p. injections of saline or one of two doses of each compound. The low and high doses of each compound were selected to be behaviorally equivalent to 2.5 and 10.0 mg/kg PCP i.p., respectively. With one exception, each dose of each drug induced an acute anticonvulsant action, with no difference in efficacy between the compounds tested. However, PCA (produced by substitution of an amine for the piperidine ring of PCP) induced a statistically greater anticonvulsant action at the higher, compared to the lower, dose. In addition, PCA was the only compound to eliminate all motor signs of the electrically induced seizure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The convulsant and anticonvulsant effects of phencyclidine (PCP) and PCP analogues in the rat. 396 7

Male Long-Evans rats were kindled via daily electrical stimulation of the left prepyriform cortex. The animals were then used in two experiments which examined the pharmacological basis of cocaine's effects on three mutually exclusive components of the kindled seizure, which were the following: (a) latency to clonus, (b) clonus duration, and (c) duration of AD outlasting clonus. The first experiment compared the effects produced by cocaine HCl (20 mg/kg, IP), lidocaine HCl (20 mg/kg, IP), and amphetamine sulfate (2.5 mg/kg, IP). The results indicated that both cocaine and lidocaine reduced the duration of kindled AD, latency to clonus, and duration of AD persisting beyond clonus, thus suggesting that these cocaine effects are mediated by local anesthetic mechanisms. Only cocaine reduced clonus duration, which suggests that this cocaine effect is not produced by a local anesthetic action. The second experiment examined the effects of cocaine following the administration of three dose levels of the monoamine antagonists haloperidol, prazosin, yohimbine, propranolol, or metergoline (selected for their ability to block dopamine, alpha-1-norepinephrine, alpha-2-norepinephrine, beta-norepinephrine, and serotonin receptors, respectively). The results of this experiment found no support for a monoaminergic contribution to cocaine's effect on clonus latency or AD after clonus. However, results for prazosin, which reduced clonus duration and exhibited an additive effect with cocaine on this variable, suggest that cocaine's norepinephrine action (especially on the alpha-norepinephrine systems) may modulate clonus duration.
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PMID:Monoaminergic and local anesthetic components of cocaine's effects on kindled seizure expression. 399 58

The purpose of this study was to examine the benzodiazepine-like activity of fominoben-HCl, a compound with prominent antitussive and respiratory stimulant actions. Towards this end we examined the anticonvulsant actions of fominoben as well as its ability to displace benzodiazepine (BDZ) binding from brain membranes. Scatchard analysis of binding data demonstrated that fominoben displaced 3H-flunitrazepam binding from rat cortical membrane preparations. Furthermore when tested against 3H-ethyl-beta-carboline-3-carboxylate, the addition of GABA resulted in a mean (+/- SE) shift of the IC50 from 4.05 +/- 0.10 microM to 2.2 +/- 0.05 microM, a characteristic of benzodiazepine agonists. Seizures were induced in male, Swiss Webster mice with pentylenetetrazol (PTZ) or 3-mercaptoproprionic acid (3-MP). Fominoben (50 and 100 mg/kg) completely protected mice from seizures induced by 50 mg/kg PTZ and elevated the seizure latency against 75 mg/kg of PTZ. The anticonvulsant effects of fominoben were less pronounced against 3-MP-induced seizures. The benzodiazepine antagonist Ro 15-1788 antagonized the anticonvulsant action of fominoben against both convulsants. Taken together, these data suggest that the anticonvulsant action of fominoben may be mediated by agonistic actions at benzodiazepine binding sites.
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PMID:Anticonvulsant actions of fominoben: possible involvement of benzodiazepine receptors. 608 74

In the experiment, rats were trained to discriminate 5 mg/kg cocaine HCl from saline in a two-bar drug discrimination procedure. Stimulus generalization experiments were carried out with six inhibitor drugs of monoamine oxidase. The rank order of absolute potency of these drugs in inducing stimulus generalization with cocaine was: tranylcypromine (ED50 in mg/kg; 1.2)>pheniprazine (3.5)>deprenyl (5)>pargyline (28)>nialamide (approximately 170); at up to 40 mg/kg, clorgyline failed to produce 50% generalization. All six drugs also potentiated tryptamine in producing body tremors and clonic seizures, the rank order of potency being tranylcypromine (0.081)>clorgyline (0.14) greater than or equal to pheniprazine (0.15)>pargyline (1.97)>deprenyl (15.5)>nialamide (18.7). Tryptamine is a common substrate for both type A and type B monoamine oxidase, so that tryptamine potentiation may serve to determine the relative specificity of the doses at which the inhibitor drugs generalized with cocaine. The present data may suggest that endogenous substances which are preferred substrates for type B monoamine oxidase in rat brain can exert control of behavior by virtue of cocaine-like stimulus properties. beta-Phenylethylamine, more so than dopamine, appears to be candidate substance for mediating the discriminative stimulus properties of cocaine and, perhaps, of other central nervous system stimulants.
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PMID:Evidence that a preferred substrate for type B monoamine oxidase mediates stimulus properties of MAO inhibitors: a possible role for beta-phenylethylamine in the cocaine cue. 610 35

Antidepressant drug overdoses have been reported to induce seizures, but the etiology of this phenomenon is still unclear. Recently we treated three patients who suffered from epileptic seizures after acute overdoses of three antidepressant drugs: (a) Dibenzepin HCl (Noveril), (b) Maprotiline HCl (Ludiomil), and (c) Clorimipramine (Anafranil). After a review of the pertinent literature, the possible role of antidepressant drugs in the genesis of epileptic seizures is discussed.
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PMID:Convulsive attacks due to antidepressant drug overdoses: case reports and discussion. 613 96

The specificity of procaine as a limbic epileptic focus activator was investigated in rats kindled in the amygdala. Power spectral analysis of spontaneous EEG was employed to assess the effects of two doses of procaine HCl (60 and 100 mg/kg) on the kindled and unkindled amygdala. Analysis revealed a dose-dependent increase in power in the 1--15 c/sec frequency band of the EEG. Power increases were greater in the kindled than in the unkindled amygdala of the same rat, and exceeded power changes induced in unkindled controls. The effects of procaine on the EEG persisted past the day of injection, but returned to baseline by the fifth day. Changes in power over days following an injection of procaine differed in the kindled and unkindled amygdala amygdala of the same rat. The kindled amygdala showed an increase on the day of injection, followed by a steady decline to baseline. The unkindled amygdala showed a delayed rise in power on day 2 and then a decline to baseline levels over days. Comparison of spectral changes induced by drug and by electrically triggered seizures suggested that procaine induces EEG patterns which are seizure-like in the absence of seizures. The data are consistent with the view that procaine may be a useful focus specific activator in the detection of limbic epilepsy.
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PMID:Power spectral analysis of EEG drug response in the kindled rat brain. 617 11

Treatment of the rat with U18666A [3 beta-(2-diethylaminoethoxy) androst-5-en-17-one HCl] resulted in development of a chronic seizure state and 20-40% reductions in the concentration of all major phospholipid in whole brain. The mechanism of the phospholipid changes was explored in the present study. Incorporation of intracerebrally injected [1,3-3H]glycerol and [32P]orthophosphate into glycerolipids was decreased by 30-40% in treated rats. U18666A added in vitro to brain slices totally blocked glycerolipid synthesis at a high drug level (10(-3) M) but stimulated incorporation into diacylglycerol, phosphatidic acid and phosphatidylinositol at a lower level (10(-4) M). When added in vitro to cell fractions from liver or brain, U18666A readily inhibited phosphatidate phosphohydrolase and the acyltransferase enzymes which convert glycerolphosphate to phosphatidic acid and which convert diacylglycerol to triacylglycerol. Fifty percent inhibition of all three enzymes occurred at drug concentrations of between 0.4 and 1.0 mM. Phosphatidate cytidylyltransferase, an enzyme important to formation of phosphatidylinositol, was comparatively resistant to inhibition. Taken together, the results indicate that the marked reduction in the concentration of brain phospholipids caused by treatment of the young rat with U18666A is likely due to decreased phospholipid synthesis secondary to inhibition of several key enzymes in glycerolipid synthesis and, particularly, to inhibition of glycerolphosphate acyltransferase and phosphatidate phosphohydrolase.
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PMID:Mechanism of depression of brain phospholipid levels by an epileptogenic drug. 670 75

Viloxazine HCl is evaluated as an anticonvulsant in a wide range of rodent seizure models and in the epileptic baboon (Papio papio). In the maximal electroshock test, the oral ED50 for abolition of tonic extension was 9 mg/kg-1 after 30-min pretreatment (mouse) rising to 30 mg/kg-1 after 60 min (mouse and rat). Comparable ED50 values were also found for protection against tonic extension in the mouse induced by the administration of the chemical convulsants metrazole or 3-mercaptopropionic acid. In DBA/2 mice the ED50 for abolition of tonic extension during sound-induced seizures was 6.8 mg/kg-1 IP (30-min pretreatment). Pharmacokinetic studies in the mouse showed peak plasma levels to occur 30 min following oral doses, with a mean half-life of 58 min. The anticonvulsant plasma concentration was within 0.5 -- 1 microgram/ml-1. In the baboon, significant protection against photomyoclonic responses is observed 1 -- 2h after viloxazine (2.6 mg/kg-1 IV), during which period the plasma concentration was again 0.5-1 microgram/ml-1. After administration of approximately ten-times this latter dose level, i.e. 24 mg/kg-1 IV, a syndrome characterised by an abnormal EEG and, in some instances, seizure activity was observed.
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PMID:Anticonvulsant and proconvulsant properties of viloxazine hydrochloride: pharmacological and pharmacokinetic studies in rodents and the epileptic baboon. 680 38

Moyamoya disease is a cerebrovascular disease characterized radiologically by progressive narrowing and occlusion of the arteries contributing to the circle of Willis and its branches. There is formation of an exuberant collateral network of blood vessels at the base of the brain, which is thought to arise in response to chronic ischemia. Clinically, the course is variable, with patients having repeated transient ischemic attacks, strokes, migraine, and seizures. Effective treatment is not available. The etiology and pathophysiology of moyamoya disease are largely unknown. Two patients with arteriographically proven moyamoya disease were identified. Both patients were symptomatic before age 5 years. Despite successful encephaloduroarteriosynangiosis revascularization procedures, they continued to experience an inexorable downhill course. A calcium channel blocker (nicardipine HCl) was introduced in order to prevent further symptoms. After the introduction of nicardipine, no further strokes occurred in either patient. There were no further episodes of transient ischemic attacks, seizures, or headache in one patient and decreased frequency in the other. In patients with moyamoya disease, nicardipine may have a beneficial effect on cerebral hemodynamics and may prevent ischemic sequelae by optimizing existing collateral circulation.
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PMID:Use of a calcium channel blocker (nicardipine HCl) in the treatment of childhood moyamoya disease. 782 27


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