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)

Roles for melatonin, taurine, and the pineal gland in epilepsy are examined. Cerebrospinal fluid melatonin and taurine may be natural anticonvulsants. The flow of cerebrospinal fluid may bathe the medial and lateral geniculate ganglia and the superior and inferior colliculli with these anticonvulsant substances. Supplemental dietary taurine and tryptophan could be of value in the treatment and prevention of seizures.
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PMID:Could supplementary dietary tryptophan and taurine prevent epileptic seizures? 385 69

Intravenous administration of digitoxigenin (DTXGN) evokes seizure episodes in mice which may be dependent on brain biogenic amines such as serotonin (5-HT). Fasting is known to have effects on both drug toxicity and brain 5-HT synthesis. The purpose of this study was to assess the effects of overnight fasting on DTXGN toxicity. The i.v. LD-50 of DTXGN was increased by 61% in fasted mice. Adjustment of DTXGN dose for the decrease in body weight of fasted mice did not alter the fasting induced protection. A loading dose of 1-tryptophan (25 mg/kg, i.p.) did not alter mortality rates in either fed or fasted mice. Cortical levels of 3H-DTXGN were decreased significantly by 25% in fasted mice. Liver and blood levels were elevated significantly. These data suggest that decreased DTXGN toxicity is associated with a decrease in its distribution to the cerebral cortex and emphasize the importance of acute dietary status in the expression of drug toxicity.
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PMID:Altered distribution and toxicity of digitoxigenin in fasted mice. 402 39

L-Tryptophan, the amino acid precursor of serotonin and several other monoamines, has frequently been employed as an adjunct with tricyclic antidepressants and monoamine oxidase inhibitors to increase their effectiveness in treating affective disorders. Combined use of L-tryptophan with electroconvulsive therapy (ECT) has generally not been successful and, in fact, may actually have a deleterious effect upon treatment. A case of decreased seizure duration due to an L-tryptophan-ECT interaction is presented and its implications discussed.
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PMID:Effect of L-tryptophan on electroconvulsive therapy seizure time. 403 41

We previously reported that 6-methoxy-1,2,3,4-tetrahydro-beta-carboline (6-MeO-THBC) attenuated audiogenic seizures (AGS) in 21-day-old DBA/2J mice and also inhibited brain monoamine oxidase-A (MAO-A) and serotonin (5-hydroxytryptamine, 5-HT) uptake leading to increased brain 5-HT concentration. In this study, the sensitivity of AGS to 5-HT manipulation was evaluated by utilizing drug combinations which paralleled the actions of 6-MeO-THBC and which also have been associated with the production of a serotonergic motor syndrome in rats. Combination of a specific 5-HT uptake inhibitor (fluoxetine or citalopram) with the MAO-A inhibitor clorgyline inhibited AGS more effectively than the individual drugs but combination with the MAO-B inhibitor deprenyl did not. Combined administration of clorgyline plus deprenyl also suppressed AGS. Inhibition of AGS by tryptophan was potentiated by combination with either of the mixed MAO inhibitors nialamide or tranylcypromine. The effects of these drugs individually and in combination on brain MAO-A and MAO-B activity and 5-HT uptake were also determined ex vivo and were consistent with expected mechanisms of action. These results suggest, first of all, that the inhibition of AGS produced by 6-MeO-THBC is a consequence of its combined MAO-A and 5-HT uptake inhibition properties. Secondly, the similarity of results of pharmacological manipulations of the 5-HT system which produce the rat motor syndrome and which inhibit AGS in the mouse suggests that AGS in 21-day-old DBA/2J mice may be a useful system for assessing functional consequences of these serotonergic manipulations.
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PMID:Combined inhibition of serotonin uptake and oxidative deamination attenuates audiogenic seizures in DBA/2J mice. 408 Jul 61

This review examines the interaction of pyridoxal phosphate with select neuroendocrine and neuropharmacological systems and their health related therapeutic implications. Vitamin B6 and its vitamers can be involved in many interactions with a number of drugs as well as the actions of various endocrines and neurotransmitters. Nutritional deficiencies, particularly of vitamins and proteins, can affect the manner in which drugs undergo biotransformation and thus may modify the therapeutic efficacy of certain drugs. In addition to pyridoxine deficiency adversely affecting drug actions, improper supplementation with viatmin B6 can in some instances also adversely affect drug efficacy. A decrease by pyridocxine in the efficacy of levodopa used in the treatment of Parkinsonism is an example. The interrelationships and enzymatic interconversions amony pyridoxine vitamers, both phosphorylated and nonphosphorylated, are briefly discussed, particularly concerning their pharmacokinetic properties. The chronic administration of isoniazid for the prevention or treatment of tuberculosis can produce peripheral neuropathy which can be prevented by the concurrent administration of pyridoxine. An acute toxic overdose of isoniazid causes generalized convulsions, and the intravenous administration of pryidoxine hydrochloride prevents or stops these seizures. The acute ingestion of excessive monosodium glutamate will, in some persons, cause a group of symptoms, including headache, weakness, stiffness, and heartburn, collectively known as the "Chinese Restaurant Syndrome." These symptoms can be prevented by prior supplementation with vitamin B6. It is postulated that the intestinal absorption of zinc is facilitated by picolinic acid, a metabolite of tryptophan. The derivation of picolinic acid from tryptophan depends on the action of the enzyme kynureninase, which is dependent on pyridoxal phosphate. Therefore, the adequate absorption of zinc is indirectly dependent on an adequate supply of vitamin B6. The formation of pyridoxal phospate appears to be indirectly dependent on Zn2++ which activates pyridoxal kinase. Treatment with daily pyridoxine can reverse a state of depression induced in women who take oral contraceptives (OCs). 1 hypothesis to explain this effect is that the OC is somehow causing a deficiency of seroton serotonin in the brain and that the vitamin B6 helps to overcome this deficiency through the stimulation of 5-hydroxytryptophan decarboxylase by pyridoxal phosphate. In sum, the stimulation of 5-hydroxytryptophan decarboxylase by pyridoxal phosphate. In sum, pyridoxal phosphate in physiological concentrations seems to function as an endogenous "down regulator" of several receptor sites, including estrogen, progesterone, and androgen.
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PMID:Drug-pyridoxal phosphate interactions. 608 25

The therapeutic activity of tryptophan and the serotonin blood level in epileptic patients were studied. A group of patients (24 cases) received tryptophan (a source of serotonin synthesis in the organism per os during three weeks in a dose of 0,25 g thrice daily. The studies demonstrated the decreased initial level of blood serotonin in patients, especially in those with frequent epileptic seizures and with the disease of long standing. The intake of tryptophan even after a week of its administration produced a reliable increase in the level of blood serotonin and suggestive changes in the clinical picture. This was especially noticeable in patients with seizures of the grand mal tupe and personality changes.
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PMID:[Therapeutic activity of tryptophan and its effect on serotonin metabolism in epilepsy patients]. 615 8

Eleven patients with long-standing progressive myoclonus epilepsy, PME, and age- and sex-matched epileptic controls received L-tryptophan (L-Trp) 100 mg/kg body weight combined with carbidopa in addition to their usual anticonvulsant regimen. During six weeks of the trial an improvement in activities of daily living and a decrease of action myoclonus was noted in the PME patients. The frequency of seizures compared with the past year decreased significantly in the PME patients, but not in the epileptic controls. Changes in the EEGs of the PME patients were scant, but a slight decrease was noted in myoclonic spikes. Both plasma Trp and platelet 5-HT increased significantly and at least as much as in epileptic controls. 5-HIAA and HVA concentrations in the CSF of the PME patients increased significantly during the trial. The results support previous findings concerning Trp treatment in PME, and longer trials with Trp + carbidopa could be of value in this disease.
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PMID:L-tryptophan-carbidopa trial in patients with long-standing progressive myoclonus epilepsy. 617 51

In this study, several biochemical aspects of serotonergic neurons were compared in mice susceptible to audiogenic seizures (Frings) and in mice not susceptible to audiogenic seizures (CF 1). Tryptophan hydroxylase (TPH) activity was significantly lower in brains of Frings mice compared to CF1 mice; however, brain levels of 5-HT were similar in both strains. The significantly lower TPH activity in Frings mice was due to the altered kinetic characteristics of TPH activity in this strain. TPH from Frings mice had a significantly lower apparent maximal velocity and a significantly higher affinity for the substrate, as indicated by a lower apparent Km for tryptophan. The uptake of tryptophan and accumulation of 5-HT (following pargyline) were similar in Frings and CF 1 mice. The levels of 5-HT in selected brain regions of Frings and CF 1 mice were also similar, but NE levels were higher in the cerebral cortex and DA levels were higher in the neostriatum of Frings mice. It is unclear at this point what role, if any, 5-HT plays in susceptibility to audiogenic seizures in brains of Frings mice.
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PMID:Altered neurochemical parameters in the brains of mice (Frings) susceptible to audiogenic seizures. 618 Aug 4

Recent data and concepts concerning the convulsant effects of kynurenines, neuroactive metabolites of tryptophan, in mice, rats, and frogs are reviewed. Myoclonic seizures of the hindlegs are induced in mice by l- and d,l-kynurenine. Both l- and d,l-kynurenine exhibit a selective synergism with strychnine. The convulsant effect of l-kynurenine is selectively antagonized by taurine, less selectively by l-glycine, and not at all by gamma-aminobutyric acid (GABA) or the GABA agonist muscimol. Derivatives of GABA and some standard anticonvulsant drugs alter seizures induced by l-kynurenine and quinolinic acid in different ways. The involvement of brian kynurenines in the genesis of epileptic seizures is suggested.
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PMID:Kynurenines and seizures. 626 4

Nicotinamide (NAM, 1000 mg/kg), inosine (INS, 1000 mg/kg), hypoxanthine (HXT, 500 mg/kg), putative endogenous ligands of the benzodiazepine receptor, and nicotinic acid (NA, 500 mg/kg) diminished DL-kynurenine-(DL-K, 50 micrograms ICV) induced seizures in C57BL/6 adult male mice and only prolonged the latency of pentylenetetrazol (PTZ, 500 micrograms iCV) seizures. The same effect was previously observed when PTZ was administered IP. In albino male BALB/c and SHR (bred from Swiss) mice only NA was effective against DL-K. Diazepam in a dose of 0.5 mg/kg prevented PTZ-induced seizures in half of the animals but even in dose of 10 and 20 mg/kg it was ineffective against DL-K. When injected ICV NAM (1 and 10 micrograms), INS (10 micrograms) and HXT (10 micrograms) prevented seizures induced by DL-K and were ineffective against seizures induced by PTZ. It is suggested that if NAM, INS and HXT are of functional importance in the central nervous system, they can act as antagonists of endogenous brain kynurenine. NA and NAM are suggested to be functional feedback inhibitory regulators of the kynurenine pathway of metabolism of tryptophan.
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PMID:Nicotinamide, inosine and hypoxanthine, putative endogenous ligands of the benzodiazepine receptor, opposite to diazepam are much more effective against kynurenine-induced seizures than against pentylenetetrazol-induced seizures. 626 99


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