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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The opioid receptor types involved in the mediation of enkephalin-induced electroencephalographic (EEG) seizures were studied in unanesthetized, freely moving rats. Four receptor-selective peptide ligands were evaluated for effectiveness in producing nonconvulsive EEG seizures after i.c.v. administration; these included the mu agonist, [D-Ala2-N-methyl-Phe4-Gly5-ol]enkephalin (DAGO), the mixed mu-delta agonist, [D-Ala2-D-Leu5]enkephalin (DADLE), and the selective delta agonists, [D-Pen2-D-Pen5]enkephalin and [D-Pen2-L-Pen5]enkephalin. Only DAGO and DADLE were found to produce EEG seizures, with DAGO being 9 times more potent than DADLE. DAGO produced a greater number of seizure episodes with a greater overall incidence compared with DADLE, reflecting its potent effect to elicit EEG seizure activity in these rats. Injections of [D-Pen2-D-Pen5]enkephalin or [D-Pen2-L-Pen5]enkephalin, even at the highest doses tested, failed to produce seizure activity. Behaviorally, the DAGO and DADLE EEG seizures were nonconvulsive but were temporally associated with episodic bursts of wet-dog shakes. The enkephalin-induced responses were extremely sensitive to antagonism by naloxone and completely blocked by pretreatment with the irreversible mu antagonist beta-funaltrexamine. The selective delta opioid receptor antagonist ICI 174,864 (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH) was ineffective. The use of the most selective agonists and antagonists for mu and delta opioid receptors suggests that, in rats, enkephalin-induced EEG seizures are mediated exclusively by mu opioid receptors and not by delta opioid systems.
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PMID:Evidence for mu opioid receptor mediation of enkephalin-induced electroencephalographic seizures. 302 18

In rats the influence of the delta opioid agonists [Leu]enkephalin, [D-Ala2-D-Leu5]enkephalin, [D-Ala2]methionine enkephalinamide and synthetic analogue of [Met]enkephalin: Tyr-D-Ala-Gly-Phe-D-Leu-OMe on audiogenic seizures was tested during ethanol abstinence. All investigated drugs significantly inhibited this ethanol withdrawal symptom. The results are compatible with the hypothesis of opioid involvement in the ethanol abstinence syndrome.
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PMID:Audiogenic seizures during ethanol withdrawal can be blocked by a delta opioid agonist. 302 46

Opioid systems seem to be implicated in the regulation of brain excitability, though in an apparently controversial way. In order to assess the involvement of mu- and delta-opioid receptors in the anti-epileptogenic properties of opioids, i.v. administrations of morphine, and of DAGO (Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol) and DTLET (Tyr-D-Thr-Gly-Phe-Leu-Thr), two peptides presenting selective agonist properties towards respectively the mu and the delta receptors, were performed on fully kindled rats. It is concluded that the mu- rather than the delta-receptors are implicated in the limitation of amygdaloid kindled seizures.
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PMID:Effects of selective mu- and delta-opioid peptides on kindled amygdaloid seizures in rats. 303 53

The artificial sweetener aspartame (L-aspartyl-L-phenylalanyl-methyl ester), is consumed, primarily in beverages, by a very large number of Americans, causing significant elevations in plasma and, probably, brain phenylalanine levels. Anecdotal reports suggest that some people suffer neurologic or behavioral reactions in association with aspartame consumption. Since phenylalanine can be neurotoxic and can affect the synthesis of inhibitory monoamine neurotransmitters, the phenylalanine in aspartame could conceiveably mediate neurologic effects. If mice are given aspartame in doses that elevate plasma phenylalanine levels more than those of tyrosine (which probably occurs after any aspartame dose in humans), the frequency of seizures following the administration of an epileptogenic drug, pentylenetetrazole, is enhanced. This effect is simulated by equimolar phenylalanine and blocked by concurrent administration of valine, which blocks phenylalanine's entry into the brain. Aspartame also potentiates the induction of seizures by inhaled fluorothyl or by electroconvulsive shock. Perhaps regulations concerning the sale of food additives should be modified to require the reporting of adverse reactions and the continuing conduct of mandated safety research.
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PMID:Possible neurologic effects of aspartame, a widely used food additive. 331 65

An association has recently been proposed between the incidence of seizures and prolonged consumption of the phenylalanine-containing artificial sweetener, aspartame. Since consumption of aspartame, unlike dietary protein, can elevate phenylalanine in brain, and thereby inhibit the synthesis and release of neurotransmitters known to protect against seizure activity, the effect of oral doses of aspartame on the sensitivity of mice to the proconvulsant agents, pentylenetetrazole and fluorothyl was studied. Doses of aspartame were used which increased phenylalanine more than tyrosine in brain, as occurs in humans after the consumption of any dose of aspartame. Pretreatment with aspartame significantly increased the percentage of animals convulsing after administration of pentylenetetrazole and significantly lowered the CD50 for this convulsant. The average time to onset of seizures induced by fluorothyl in control mice was 510 sec; pretreatment with oral doses of 1000, 1500 and 2000 mg/kg of aspartame 1 hr earlier significantly reduced the time required to elicit seizures (394, 381 and 339 sec, respectively). The seizure-promoting effect of aspartame could be demonstrated 30, 60 or 120 min after the 1000 mg/kg dose. The seizures induced by either convulsant were potentiated by equimolar amounts of phenylalanine, a major endogenous metabolite of aspartame, while the other metabolites, aspartic acid and methanol, were without effect. Administration together with aspartame of the large neutral amino acid valine, which competes with phenylalanine for entry into the brain, completely abolished the seizure-promoting effect of aspartame.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Administration of aspartame potentiates pentylenetetrazole- and fluorothyl-induced seizures in mice. 335 66

Biochemical and pharmacological effects of gamma-vinyl GABA (Vigabatrin, GVG), and irreversible enzyme-activated inhibitor of 4-aminobutyrate: 2-oxoglutarate aminotransferase (EC 2.6.1.19; GABA-T), were measured in mice. This anticonvulsant produced a time- and dose-dependent elevation of the GABA, phenylalanine and lysine contents of cortical tissue and simultaneously decreased glutamate, aspartate and alanine levels. In addition, GVG caused a biphasic change in glutamine concentrations (a decline 1-4 hours after administration, followed 20 hours later by an increase). Moreover, we found a new, as yet unidentified amino acid in the brain eluting with the same retention time as alpha-aminoadipic acid from an HPLC cation-exchange column. The level of this novel chemical entity was greatly increased by GVG 20 hours after injection of the drug. At all tested intervals between 1 and 60 hours after injection, GVG was ineffective against maximal electroshock. The GABA-T inhibitor dose-dependently protected mice against isoniazid-induced seizures, simultaneously causing an increase in brain GABA concentrations. However, this apparent correlation applied only until 4 hours after treatment. To better define the anticonvulsant profile of GVG, groups of mice were treated, 1, 2, 4, and 24 hours prior to challenge with convulsant doses of strychnine, pentetrazole (PTZ), and picrotoxin, and brain amino acid levels, including brain concentrations of GVG, were measured. In all instances, the time dependency of the anticonvulsant effects of GVG and of increases in brain GABA levels differed. Amino acid concentrations in animals treated only with GVG were similar to those in animals given GVG and a chemical convulsant. GVG showed no selectivity for seizures produced by impairment of GABA-ergic neurotransmission. Although GVG is an effective GABA-T inhibitor, it apparently affects several other pyridoxal-phosphate-dependent cerebral enzymes and/or interacts with other neurotransmitter systems as well.
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PMID:Gamma-vinyl GABA: comparison of neurochemical and anticonvulsant effects in mice. 341 34

Evidence of genetic factors in seizure disorders by examination of plasma amino acid concentrations in multiply affected sibships was investigated. The strategy of multiply affected sibship ascertainment was used to reduce heterogeneity as one of several potential sources of variation in quantitative amino acid levels. Our results do not support previously reported increases in plasma taurine, aspartic acid, or glutamic acid in seizure patients. However, we do find that multiply affected sibships have significantly elevated plasma concentrations of arginine and asparagine, and significantly decreased ornithine. These amino acid concentrations may be under quantitative genetic control. Within-sibship comparisons indicate that seizure patients have increased glutamine and decreased lysine and phenylalanine, possibly secondary to the seizures. We also find that anticonvulsant use complicates statistical analyses. Further studies to more clearly delineate the genetics of plasma amino acid concentrations (or other quantitative metabolic measures) and their role in seizure disorders are required and will benefit from the use of a homogeneous sampling strategy.
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PMID:Altered amino acid levels in multiply affected sibships with seizures. 407 67

The respiratory depression induced by two mu-opiate agonists morphine and Tyr-D-Ala-Gly-N-Me-Phe-Met(O)-ol (FK-33824), and two delta-agonists Tyr-D-Ala-Gly-Phe-D-Leu (DADLE) and Tyr-D-Ser-Gly-Phe-Leu-Thr (D-Ser2-Thr6) was studied in rats by using the intracerebroventricular route. The four opioids caused a dose-dependent depression of respiratory frequency down to apnea but high doses of morphine elicited motor activation and seizure activity. FK-33824 was the most potent, followed by DADLE, D-Ser2-Thr6 and morphine. The in vivo apparent pA2 values were determined for naloxone against FK-33824, DADLE and D-Ser2-Thr6. The pA2 value of naloxone interacting with the mu-agonist FK-33824 was significantly lower than those obtained against the two delta-agonists. It is proposed that different types of opiate receptors are involved in the opiate-induced respiratory depression.
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PMID:Interaction of naloxone with mu- and delta-opioid agonists on the respiration of rats. 630 57

Free amino acid patterns of cerebrospinal fluid in infants and children with various types of convulsive disorders were compared with those in age-matched normal subjects. The total free amino levels in Lennox syndrome were higher than the normal values, and those in infantile spasms controlled by ACTH were higher than those in uncontrolled infantile spasms. Although the levels of only one or two amino acids in tonic-clonic seizure, focal seizure and febrile seizure were higher or lower than those of the controls, the levels of 8 amino acids in infantile spasms were lower and those of 10 amino acids in Lennox syndrome were generally higher compared to the controls. Among amino acids in CSF of children with tonic-clonic seizure, infantile spasms or Lennox syndrome, only the ornithine level was commonly lower than that of the controls. After the treatment, in tonic-clonic seizure, the levels of taurine, asparagine and glycine were increased, and in infantile spasms, those of asparagine, glutamine, glycine, alanine, phenylalanine, lysine and arginine were increased while that of taurine was decreased. These results suggest that each type of convulsive disorder shows the specific amino acid pattern, and the effects of anticonvulsants may be partially understood through the changes of the free amino acid patterns in the brain.
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PMID:Amino acid metabolism in the brain with convulsive disorders. Part 3: Free amino acid patterns in cerebrospinal fluid in infants and children with convulsive disorders. 632 17

The frequency of the various degrees of the intellectual defect and convulsive syndrome was studied in 473 patients with phenylketonuria divided into four groups as regards the phenylalanine blood level, that was 150 to 199 mg/l in group I, 200 to 299 mg/l in group II, 300 to 399 mg/l in group III, and 400 mg/l and higher in group IV. A substantial increase of the number of patients with grave mental derangement and epileptic seizures was noted in groups II and IV: this shows that the risk of the grave mental affection is the greater the higher the phenylalanine serum level. An increased number of patients with a slight intellectual derangement in group I (43.2%) was noted, while in all other groups, the frequency of the mild course of the disease remained stable (about 7.5%). Possibility of existence of several pathogenic thresholds of hyperphenylalaninemia, as well as possible mechanisms of brain protection are discussed.
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PMID:[Relationship between the severity of brain damage in phenylketonuria and the degree of hyperphenylalaninemia]. 722 98


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