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)

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

Changes in amino acid concentrations were investigated in selected regions of rat brain prior to the onset and during the course of epileptiform seizures induced by L-homocysteine. The concentration of gamma-aminobutyric acid (GABA) decreased preictally in substantia nigra (-18%), caudate putamen (-26%), and inferior colliculus (-46%). After seizure onset, the GABA content was further reduced in substantia nigra (-31%) and additionally in hippocampus (-18%). Preictal taurine levels were elevated in globus pallidus (+26%) and caudate putamen (+13%) but returned to normal after seizure onset. However, in hippocampus, taurine decreased both preictally (-22%) and after seizure onset (-56%). Glycine was reduced preictally only in globus pallidus (-13%). After seizure onset the direction of its concentration change varied in the brain regions studied. Glutamate levels decreased preictally in hippocampus (-10%) and hypothalamus (-46%) but increased in globus pallidus (+14%). Normal levels were detectable after seizure onset in hypothalamus and globus pallidus but a further reduction in hippocampus (-59%) and significant reductions in substantia nigra (-15%) and caudate putamen (-17%) were detected. Aspartate was elevated in hippocampus, both preictally (+49%) and after seizure onset (+21%) while at the same phases in globus pallidus a consistent reduction (-30%) was observed. The glutamine content increased preictally in globus pallidus (+41%) and hypothalamus (+36%), and in all brain areas during the ictal phase of seizure, the hippocampus exhibiting a dramatic increase (approximately 300%). The contents of serine and alanine were altered in most regions studied only after seizure onset, with the exception of the hippocampus, where a decrease (-41%) of serine was observed preictally.
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PMID:Differential changes in the content of amino acid neurotransmitters in discrete regions of the rat brain prior to the onset and during the course of homocysteine-induced seizures. 287 Jan 35

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

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 DDT syndrome in rats consists of tremor, myoclonus, running seizures, hyperthermia, episodic boxing, and excessive grooming. DDT did not change whole-brain glycine levels when the rats had stimulus-sensitive myoclonus, spontaneous myoclonus, or seizures. However, regional analysis showed a decrease in glycine levels in the pons and medulla initially, but they rose again despite worsening of the myoclonus. Glycine given intraventricularly and the glycine prodrug, milacemide, given intraperitoneally suppressed DDT-induced myoclonus. A dose of milacemide that prevented DDT-induced myoclonus caused a significant increase in glycine levels in cortex, septum accumbens, cerebellum, striatum, hippocampus diencephalon, midbrain, pons, and medulla. The increase was most marked in the forebrain structures. There was no change in serine levels in these areas. These data suggest that the glycinergic system may be playing an important role in the manifestation of DDT-induced myoclonus.
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PMID:Glycine involvement in DDT-induced myoclonus. 317 67

The effect of glycine on the anticonvulsant activity of diazepam and phenobarbital in fully developed kindled amygdaloid seizures in rats was determined. Glycine alone had no significant effect on the seizure response, either when administered orally 1 hr prior to the seizure test or when given chronically in a 0.5 M solution as the source of water. Administration of glycine (10 mmol/kg, oral) together with diazepam produced a significant reduction in both cortical epileptiform afterdischarge and the severity of seizures at doses of diazepam which had no significant effect on the seizures when administered alone. Glycine potentiated the effects of phenobarbital on the cortical afterdischarge but not the severity of the seizures. The observed potentiation of the effects of diazepam and phenobarbital suggests a glycinergic mechanism in the anticonvulsant action of these drugs which may be mediated in part by the inhibitory gamma-aminobutyric acid (GABA) systems.
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PMID:Glycine potentiates the anticonvulsant action of diazepam and phenobarbital in kindled amygdaloid seizures of rats. 356 14

Glycine or its receptor antagonist, strychnine, were administered perispinally to investigate their effect on nociceptive responses elicited by activation of various cutaneous receptors. Strychnine produced dose-dependent sensory and motor disturbances; 1 and 5 micrograms doses were sub-convulsive, eliciting recurrent episodes of coordinated grooming, scratching and biting at the skin, which persisted for approximately 10 minutes post-injection; higher doses (25 and 100 micrograms) increased the intensity and duration of these effects, and produced convulsive motor seizures. Motor disturbances were not elicited by glycine (5, 25, 100 and 400 micrograms). Strychnine treated rats, at all doses, vocalized consistently in response to light cutaneous stimulation; a significant proportion of glycine treated rats also vocalized, but were not as sensitive to mild stimulation. Skin hyperalgesia persisted for at least 30 minutes in both strychnine and glycine treated rats. Both strychnine and glycine significantly reduced vocalization thresholds to tail shock. However, no clear effect on tail flick latency was observed following either strychnine or glycine. These results indicate that glycinergic neurons contribute to the tonic regulation of nociceptive input at the spinal cord.
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PMID:Hyperalgesia induced by altered glycinergic activity at the spinal cord. 383 86

Extracellular levels of amino acids were estimated in dialysates of the rat striatum that were collected 1, 2, and/or more than 5 days after surgery, before (resting release) and during exposure to high K concentrations (50 mM) or electroconvulsive shocks. The resting release of several amino acids (Glu, Asn, Thr, Tau, Tyr, Gly, and Ala) was higher 9 days as compared to 1 day after surgery. In the 1-day preparation the resting release correlated highly with that observed with push-pull cannulas. The correlation with the tissue content of the amino acids was high only when they were divided into two groups (putative transmitters and metabolic intermediates). High K exposure produced increased output of Ala, ethanolamine (Eam), Asp, Glu, Tau, and Gly and a decrease in the egress of Gln 1 or 2 days after surgery. The effects on Asp and Glu had disappeared, and that on Gln reversed after 4-9 days. Electrically induced convulsions produced increased output of Ala, Gln, and Eam 1 or 2 days and 2 weeks after implantation of the probe. Changes were seen not only during but also (and some cases even more prominent) after the seizure. This study shows the usefulness of dialysis to monitor extracellular transmitter amino acids in the striatum of conscious rats (also bilateral dialysis was possible) for only a limited time after implantation of the probe. The dialysis method is suitable for longer time, when metabolic changes in amino acids are to be followed. In addition to transmitter release, glycolysis can be monitored by the measurement of Ala in the dialysate.
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PMID:Amino acids in rat striatal dialysates: methodological aspects and changes after electroconvulsive shock. 404 52


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