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

Oral administration of the artificial sweetener aspartame, 1 g/kg, or of an equimolar dose of its metabolite phenylalanine, to fasted rats 1 hour before slow i.v. infusion of theophylline until the onset of maximal seizures had no significant effect on the total dose and the serum and cerebrospinal fluid concentrations of theophylline at the pharmacologic endpoint. These findings indicate that consumption of aspartame is not a potential risk factor for theophylline-induced neurotoxicity.
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PMID:Aspartame and phenylalanine do not enhance theophylline-induced seizures in rats. 261 98

The effects of excessive doses of phenylalanine on seizure susceptibility were examined in animal models in the past, primarily because of their relevance to phenylketonuria. It was thought that such effects might involve brain monoaminergic mechanisms. Recently, this issue has been pursued with a renewed interest but for a different reason. The dipeptide sweetener, aspartame, contains a phenylalanine residue. In the last three years, a number of studies involving as many as nine animal models of seizures have reexamined the effects of phenylalanine (and aspartame) on seizure thresholds. Data from these studies are in general agreement that aspartame at dosage levels below 1,000 mg/kg, or phenylalanine at equimolar doses, is without an effect on seizure susceptibility in animals. When the dosage level of aspartame reaches 1,000 mg/kg, the findings between various laboratories and from different animal models of seizures are inconsistent, showing either no effect or a proconvulsant effect. The Acceptable Daily Intake of aspartame in humans set by the Food and Drug Administration is 50 mg/kg/day. Thus, the data from the excessive bolus doses in rodents do not appear to be relevant to human use. This article provides a detailed review of the data from both early and recent studies and points out the methodological problems apparent at such high doses.
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PMID:Pharmacological effects of phenylalanine on seizure susceptibility: an overview. 265 69

The effect of aspartame administered by gavage to rats on amygdala and hippocampal kindled seizures was assessed. Despite the administration of a wide range of doses (25-2000 mg/kg) no evidence for an effect of aspartame on afterdischarge threshold or seizure strength was obtained when testing was done at a time when serum and brain levels of neutral amino acids are known to be significantly elevated as a result of this treatment. There is controversy whether dietary aspartame (N-L-aspartyl-L-phenylalanine 1-methyl ester), a food additive sweetner, can lead to seizures in susceptible humans and in laboratory animals. A proseizure effect of high consumption of aspartame has been alleged (Wurtman, 1985; Walton, 1986) and denied (Gaull, 1985). Recent studies using mice have yielded mixed results. Thus, Kim and Kim (1986) and Pinto and Maher (1988) observed potentiating effects of high loads of aspartame on chemically induced seizures, but Nevins, Arnolde and Haigler (1986) observed no effect on chemical and ECS seizures. We used the electrical kindling model of epilepsy to assess whether aspartame can alter seizure threshold or strength in rats. The kindled response is highly repeatable and stable and has been shown to be sensitive to a large variety of pharmacological treatments (Racine, 1978) and to dietary manipulation (McCann, Cain and Philbrick, 1983).
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PMID:Failure of aspartame to affect seizure susceptibility in kindled rats. 274 53

Hyperphenylalaninemia in infants and children may be caused by a deficiency of dihydropteridine reductase (DHPR). Recommended therapy includes folinic acid as a source of tetrahydrofolate, a phenylalanine-restricted diet, and both dopamine and serotonin precursors. We report a child with progressive basal ganglia and other subcortical calcifications prior to the use of folinic acid. Six other reported cases of DHPR deficiency demonstrated similar calcifications prior to folinic acid therapy. Since this pattern of calcification also resembles that seen in CNS folate deficiency caused by both congenital folate deficiency and that which is methotrexate-induced, we propose that intracranial calcification in DHPR deficiency is caused by inadequate CNS tetrahydrofolate and may be prevented by the use of folinic acid. Our patient achieved excellent seizure control following the use of folinic acid, suggesting either a direct or indirect anticonvulsant effect of this compound in patients with DHPR deficiency.
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PMID:Progressive intracranial calcification in dihydropteridine reductase deficiency prior to folinic acid therapy. 278 51

Phenylketonuria (PKU) is a congenital defect involving failure to metabolize phenylalanine to tyrosine because of the absence of phenylalanine hydroxylase. Untreated PKU causes severe mental retardation, musty odor, hyperactivity, seizures, eczema and hypopigmentation. Without therapy, the child may develop with an IQ of less than 20. Restricting dietary phenylalanine before the onset of brain damage is necessary, to maintain the phenylalanine concentration at 3-8 mg/dl. Thirteen thousand three hundred and ninety-seven mentally retarded outpatients, aged 4 months to 24 years, from the year 1963 to 1987 were studied for PKU. Seven patients had positive PKU test by ferric chloride test and Phenistix, six PKU confirmed by paper chromatography. Two PKU by fluorometry and one PKU by amino acid analyzer. The incidence is 1:1,900 mentally retarded patients or 1:1,200,000 population. So, the incidence seems to be lower than in other countries which have neonatal screening for PKU. Because early diagnosis is essential in order to avoid the severe effects of PKU, neonatal screening has become widespread in the U.S., Australia, Great Britain, and other European Countries. The incidence of 1 PKU out of 1:1,200,000 Thai population seems to be not important enough for initiation of a PKU screening program in Thai newborns.
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PMID:The incidence of phenylketonuria in Thailand. 280 57

Seven L-amino acids (Trp, Arg, Lys, Met, Ile, Val, and Phe) partially (28-81%) reversed the inhibitory action of 1 microM gamma-aminobutyric acid (GABA) on t-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding to rat brain membranes, with EC50 values ranging from 5 to 120 mM. D-Trp, D-Arg, D-Lys, D-Met, D-Val, and D-Phe were approximately equipotent with their L-isomers. Tyramine, phenethylamine, and tryptamine, the decarboxylation products of the aromatic amino acids (Tyr, Phe, and Trp, respectively), reversed the inhibitory action of 1 microM GABA on [35S]TBPS binding more potently than the parent amino acids (EC50 values = 1.5-3.0 mM). Human hereditary amino acidemias involving Arg, Lys, Ile, Val, and Phe are associated with seizures, and these amino acids and/or their metabolites may block GABA-A receptors. Five other L-amino acids (ornithine, His, Glu, Pro, and Ala) as well as Gly and beta-Ala inhibited [35S]TBPS binding with IC50 values ranging from 0.1 to 37 mM, and these inhibitions were reversed by the GABA-A receptor blocker R 5135 in all cases. The inhibitory effects of L-ornithine, L-Ala, L-Glu, and L-Pro were stereospecific, because the corresponding D-isomers were considerably less inhibitory. L-His, D-His, and L-Glu gave incomplete (plateau) inhibitions. Human hereditary amino acidemias involving L-ornithine, His, Pro, Gly, and beta-Ala are also associated with seizures, and we speculate that these GABA-mimetic amino acids may desensitize GABA-A receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Two groups of amino acids interact with GABA-A receptors coupled to t-[35S]butylbicyclophosphorothionate binding sites: possible involvement with seizures associated with hereditary amino acidemias. 284 55

The purpose of this paper was to study the relationship between different neurotransmitter systems and seizure susceptibility in Mongolian gerbils with genetically determined epilepsy. In these animals, generalized tonic-clonic seizures were induced by stimulation with a blast of compressed air. A variety of drugs that specifically manipulate inhibitory or excitatory neurotransmitter systems proved capable of dose dependently blocking these seizures, i.e., the anticholinergic drug biperiden (ED50 12 mg/kg i.p.), the excitatory amino acid antagonist (+/-)-2-amino-7-phosphonoheptanoic acid (120 mg/kg), the gamma-aminobutyric acid (GABA) agonists muscimol (0.66 mg/kg), 4,5,6,7-tetrahydroisoxazolo(5,4-c) pyridine-3-ol (1.3 mg/kg), progabide (50 mg/kg) and its acidic metabolite SL 75102 (45 mg/kg), the GABA aminotransferase inhibitors aminooxyacetic acid (0.9 mg/kg), gamma-acetylenic GABA (2.1 mg/kg) and ethanolamine-O-sulfate (1000 mg/kg), the GABA uptake inhibitor (-)-nipecotic acid ethyl ester (21 mg/kg), the dopamine agonist apomorphine (approximately 5 mg/kg), the dopamine precursor 3,4-dihydroxy-L-phenylalanine (34 mg/kg), and the alpha-adrenoceptor agonists clonidine (0.38 mg/kg) and xylazine (approximately 10 mg/kg). The anticonvulsant effect of 3,4-dihydroxyl-L-phenylalanine was not significantly affected by pretreatment with the dopamine-beta-hydroxylase inhibitors disulfiram and diethyldithiocarbamate, thus strongly indicating that 3,4-dihydroxyl-L-phenylalanine was acting through increase in dopamine rather than noradrenaline levels in the brain. The (+)-isomer of nipecotic acid ethyl ester, the glycineamide derivative milacemide, the indirect 5-hydroxytryptamine agonist fenfluramine and the 5-hydroxytryptamine antagonist ketanserin exerted no anticonvulsant action. The 5-hydroxytryptamine precursor L-5-hydroxytryptophan and the dopamine agonist lisuride were only weakly active but exerted pronounced side effects in the animals. Weak anticonvulsant effects were also determined for atropine, the noradrenaline precursor DL-threo-3,4-dihydroxyphenylserine and the excitatory amino acid antagonist (+/-)-2-amino-5-phosphonopentanoic acid. Comparison of anticonvulsant potencies of the various drugs in gerbils with potencies reported in other genetic animal models of epilepsy, such as audiogenic seizure-susceptible mice, indicated that drugs that increase GABA and dopamine levels in the brain are strikingly more effective in gerbils than in other species in blocking generalized seizures.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Influence of pharmacological manipulation of inhibitory and excitatory neurotransmitter systems on seizure behavior in the Mongolian gerbil. 285 79

We investigated in rats whether aspartame intake affected the susceptibility to seizures induced chemically (metrazol, quinolinic acid) or electrically (electroshock). Aspartame (0.75-1.0 g/kg), given orally as a single bolus to 16-hr fasted animals 60 min before metrazol, significantly increased the number of animals showing clonic-tonic seizures. At 1.0 g/kg the ED50 for clonic-tonic convulsions was lowered by 23%. A similar increase in seizure susceptibility was observed with 0.25-0.5 g/kg of the aspartame's metabolite phenylalanine. When aspartame was administered to fasted rats in three divided doses (0.33 g/kg) over 120 min or to fed animals after a meal, or overnight with the diet, no significant changes in the incidence of animals showing seizures was observed. One gram per kilogram aspartame and 0.5 g/kg phenylalanine did not modify the CC50 (mA) for tonic hindlimb extension induced by electroshock and the electroencephalographic seizures caused by intrahippocampal injection of 120 nmol quinolinic acid. Plasma and brain levels of phenylalanine and tyrosine significantly raised after both 1 g/kg aspartame as a single bolus (plasma: Phe 285%, Tyr 288%; brain: Phe 146%, Tyr 192%; above controls) or in three divided doses (plasma: Phe 207%, Tyr 315%; brain Phe 103%, Tyr 211%; above controls) and 0.5 g/kg phenylalanine (plasma: Phe 339%, Tyr 410%; brain: Phe 219%, Tyr 192%; above controls), but the ratio Phe/Tyr was not modified. Our data indicate that aspartame cannot be regarded as a general proconvulsant agent. The mechanisms of potentiation of seizures induced by metrazol after the administration of the sweetner in a single rapid intake will be discussed.
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PMID:Effect of aspartame on seizures in various models of experimental epilepsy. 297 54

Cortical electroencephalographic (EEG) recordings were performed on rats after i.v. administration of morphine and specific mu- and delta-opioid peptides. DAGO (Tyr-D X Ala-Gly-N X Me X Phe-Gly-ol), the mu-selective peptide, produced repetitive paroxysmal discharges organized in a pattern analogous to that seen in tonic clonic seizures at doses which produced analgesia while DTLET (Tyr-D X Thr-Gly-Phe-Leu-Thr), the delta-selective peptide, produced 'petit-mal'-like seizures at doses which caused neither analgesia nor catatonia. It is suggested that the delta receptor is preferentially implicated in the epileptogenic spectrum of opioids.
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PMID:Differential electrographic patterns for specific mu- and delta-opioid peptides in rats. 301 58

Two groups of experiments were conducted to determine if morphine- and enkephalin-induced seizures are specifically mediated by the mu and delta receptor, respectively. In the first experiments, designed to assess the ontogeny of mu- or delta-seizures, rats from 6 h to 85 days of age received implanted cortical and depth electrodes as well as an indwelling cannula in the lateral ventricle. Various amounts of the mu-receptor agonists, morphine and morphiceptin, and the delta agonists, D-Ala2-D-Leu5-enkephalin (DADL) and Tyr-D-Ser-Gly-Phe-Leu-Thr (DSLET), were then administered intracerebroventricularly (icv) with continuous EEG monitoring. The second experiments entailed use of the nonspecific opiate antagonist, naloxone, as well as the specific delta antagonist, ICI 154,129, against seizures induced by icv-administered morphine, morphiceptin, DADL, or DSLET. Both morphine and morphiceptin produced electrical seizure activity in rats as young as 5 days after birth. The drugs produced similar seizure activity in terms of electrical morphology, observed behavior, ontogeny, threshold dose, and reversibility with small doses of naloxone. In the pharmacologic experiments, icv naloxone blocked all opiate-induced seizures. ICI 154,129 blocked DSLET seizure, had little effect on enkephalin or DADL seizures, and no effect on morphine or morphiceptin seizures. These data indicate that DSLET seizures are delta-specific but that all other opiate-induced seizures studied may involve multiple opiate receptor-mediated mechanisms.
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PMID:Opiate-induced seizures: a study of mu and delta specific mechanisms. 301 59


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