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

The effects of selected drug treatments on spinal cord norepinephrine (NE), dopamine (DA), and 5-hydroxytryptamine (5-HT) were compared to the effects of these same treatments on electrically-induced spinal cord seizure. Depletion of monoamine stores by reserpine facilitated spinal cord seizures. In contrast, L-DOPA, given to animals pretreated with iproniazid, exerted an anticonvulsant effect and elevated spinal cord NE and DA levels. L-DPOA administered alone produced a substantial elevation in DA levels but had no effect on spinal cord seizures. Iproniazid had no effect on monoamines, whereas it facilitated seizure activity. These observations support the concept that spinal cord noradrenergic, but not 5-hydroxytryptaminergic or dopaminergic neurons act as attenuators of convulsive activity. The effect of iproniazid on spinal cord seizures, in the absence of an observed alteration in monoamine levels, provides evidence that this effect is mediated through non-monoaminergic mechanisms.
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PMID:The effects of reserpine, iproniazid and L-dopa on electrically-induced spinal cord seizures. 742 21

Amino acid and monoamine concentrations were examined in tissue extracts of caudate nucleus of genetic substrains of BALB/c mice susceptible or resistant to audiogenic seizures. Amino acids [aspartate, glutamate, glycine, taurine, serine, gamma-aminobutyric acid (GABA)], monoamines, and related metabolites were separated by isocratic reverse-phase chromatography and detected by a coulometric electrode array system. In situ activity of tyrosine hydroxylase and tryptophan hydroxylase were determined by measuring the accumulation of L-DOPA and 5-hydroxytryptophan after administration of the decarboxylase inhibitor NSD-1015. Highly significant decreases in concentrations of both excitatory (glutamate and aspartate) and inhibitory amino acids (GABA and taurine) were observed in extracts of caudate nucleus of seizure-prone mice. Substantial decreases in concentrations of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, were also noted. Decreased accumulation of L-DOPA after NSD-1015 administration provided evidence for decreased tyrosine hydroxylase activity and decreased DA synthesis in striatum of seizure-prone mice compared with seizure-resistant mice. Decreased concentrations of the DA metabolite 3-methoxytyramine (after NSD-1015 administration) suggested that DA release was also compromised in seizure-prone mice. No significant difference in 5-hydroxytryptophan accumulation in striatum of seizure-prone and seizure-resistant mice suggested that tryptophan hydroxylase activity and serotonin synthesis were not affected. The data suggest that seizure-prone BALB/c mice have a deficiency in intracellular content of both excitatory and inhibitory amino acids. The data also raise the issue of whether GABAergic interactions with the nigrostriatal DA system are important in the regulation of audiogenic seizure susceptibility.
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PMID:Determination of amino acids and monoamine neurotransmitters in caudate nucleus of seizure-resistant and seizure-prone BALB/c mice. 768 Nov

1. The effects of some GABAergic and dopaminergic agents on pyrimethamine-induced tonic seizures were investigated in mice. 2. Pyrimethamine dose dependently induced seizures in mice. 3. Muscimol, AOAA and DABA significantly protected mice against pyrimethamine-induced seizures. 4. Bicuculline and picrotoxin effectively potentiated seizures elicited by pyrimethamine and significantly antagonized the protective effect of muscimol against the seizures. 5. Diazepam and phenobarbitone effectively protected mice against seizures elicited by pyrimethamine. 6. L-Dopa significantly potentiated pyrimethamine-induced seizures. 7. Apomorphine and pargyline significantly reduced the latency of seizures induced by pyrimethamine. 8. Haloperidol and pimozide effectively protected mice against pyrimethamine-elicited seizures and also significantly antagonized the potentiating effects of apomorphine and L-dopa on the seizures. 9. Disulfiram significantly potentiated seizures induced by pyrimethamine and also significantly enhanced the seizure-potentiating effect of L-dopa. 10. alpha-Methyl-p-tyrosine effectively protected against seizures induced by pyrimethamine. However, L-dopa significantly potentiated the seizures in alpha-methyl-p-tyrosine-pretreated animals. 11. Muscimol significantly attenuated the potentiating effect of L-dopa on pyrimethamine-induced seizures while bicuculline significantly enhanced the effect of L-dopa. Furthermore, haloperidol significantly potentiated the protective effect of muscimol against pyrimethamine-induced seizures. 12. These results suggest that both GABA and dopamine might be involved in the mechanism(s) of pyrimethamine seizures in mice.
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PMID:GABAergic and dopaminergic systems may be involved in seizures induced by pyrimethamine in mice. 787 56

Central effects of SL 82.0715, an antagonist of polyamine site of the NMDA receptor complex, was studied in male Albino-Swiss mice. SL 82.0715, in doses which given alone were inactive in electroshock-induced seizures, potentiated the anticonvulsant effects of CGP 37849. In normal mice, SL 82.0715 decreased the spontaneous locomotor activity, did not affect the locomotor hyperactivity induced by MK-801 and attenuated CGP 37849-induced locomotor hyperactivity. The D-amphetamine locomotor hyperactivity was also antagonized by SL 82.0715. SL 82.0715 did not significantly change the locomotor activity in monoamine-depleted mice (treated with reserpine + alpha-methyl-p-tyrosine). When administered together with clonidine, SL 82.0715 increased the locomotor activity in monoamine-depleted mice but this effect did not reach the level of statistical significance. SL 82.0715 did not change the locomotor activity induced by joint administration of clonidine and MK-801 or clonidine and CGP 37849, in monoamine-depleted mice. The locomotor hyperactivity evoked by L-DOPA (given jointly with benserazide) was not changed by SL 82.0715. SL 82.0715 had no effect on fluphenazine- and haloperidol-induced catalepsy in mice. CGP 37849 attenuated catalepsy induced by haloperidol; that effect was not changed by SL 82.075. The studied compound did not affect the immobility time and had no effect on the action of MK-801 or CGP 37849 in the forced swimming test. The obtained results indicate that SL 82.0715 has a different pharmacological profile than other NMDA antagonists (at least MK-801 and CGP 37849). SL 82.0715 does not increase behavioral actions of MK-801 and CGP 37849, potentiating anticonvulsant effect of CGP 37849 only.
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PMID:Central effects of SL 82.0715, an antagonist of polyamine site of the NMDA receptor complex. 791 35

Dyskinesias commonly appear during L-dihydroxyphenylalanine (L-DOPA) therapy of advanced Parkinson's disease (PD) and can occur in both dose-related and dose-independent patterns. Clozapine exerts a dose-related suppression of L-DOPA-induced dyskinesias by shifting the i.v. L-DOPA dose-response curve for production of dyskinesias without altering relief of parkinsonism. We report our outpatient experience with 13 patients on daily clozapine therapy (maximum dose 400 mg/day), followed for 3-21 months (median 10). Beneficial effects of clozapine, determined from twice-weekly diaries, included increased "on time" and decreased "off time" and time "on with dyskinesia." Improvements were statistically apparent by 75 mg/day and remained so through 200 mg/day. Sedation was a common problem, reflected by increased time "asleep" which was significant by 50 mg/day. Sedation was dose limiting in most patients. Orthostatic hypotension and sialorrhea were variably present. No patients had seizures, bone marrow toxicity, or detectable loss of efficacy of clozapine with chronic use. We conclude that clozapine is an effective agent for suppression of dyskinesias in PD with an effective daily dose for most patients of 100-200 mg/day.
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PMID:Suppression of dyskinesias in advanced Parkinson's disease: moderate daily clozapine doses provide long-term dyskinesia reduction. 796 7

Strychnine-insensitive glycine site is one of a few binding sites of NMDA receptor complex. The aim of these study was to find out whether compounds regarded as glycine antagonists-kynurenic acid (KA), 7-chlorokynurenic acid (7-CKA), 5,7-dichlorokynurenic acid (5,7-DCKA) evoke the effects analogous to those of the NMDA receptor antagonist, CGP 37849 (or MK-801) and/or can modulate the effects of the last compounds in rats. KA (but not 7-CKA, given ip) inhibited electroshock-induced seizures and increased the anticonvulsant effect of CGP 37849. CGP 37849-induced locomotor hyperactivity was enhanced by KA, 7-CKA (icv but not ip) and 5,7-DCKA. D-Amphetamine-induced hyperactivity was inhibited by KA as well as 7-CKA. In monoamine-depleted rats 7-CKA (but not KA) increased the antiakinetic effect of clonidine; the antiakinetic effect of L-DOPA was enhanced by 7-CKA and 5,7-DCKA, but not by KA. KA and 7-CKA did not change the spiperone-induced catalepsy but they attenuated the anticataleptic effect of CGP 37849; the studied drugs did not change the anticataleptic effect of MK-801. 7-CKA given icv did not influence the spiperone-induced catalepsy as well as the anticataleptic effect of CGP 37849. In the forced swimming test KA, given once, prolonged (50 mg/kg) or did not change (200 and 300 mg/kg) the immobility time. 7-CKA did not affect the immobility time in this model. When given three times KA (200 mg/kg) and 7-CKA (20 mg/kg) reduced the immobility time; the lower doses of KA and 7-CKA prolonged or did not change the immobility time, respectively. Joint injection with imipramine and KA (or 7-CKA) induced the decrease of immobility time (vs imipramine alone or glycine antagonist alone); in the case of joint injection with citalopram + KA (or 7-CKA), the time of immobility was prolonged or not changed. In conclusion, the obtained results point to similarities between glycine antagonists (kynurenine derivatives) and CGP 37849 and to the possibility of positive cooperation between the NMDA- and glycine-sites antagonists.
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PMID:Some central effects of kynurenic acid, 7-chlorokynurenic acid and 5,7- dichloro-kynurenic acid, glycine site antagonists. 800 Apr 42

The influence of some dopaminergic and noradrenergic agents on seizures induced by chloroquine (45-100 mg/kg, i.p.) was investigated in mice. Apomorphine (0.2-0.8 mg/kg, s.c.). L-dopa (25-50 mg/kg, s.c.) benserazide (5 mg/kg, i.p.) plus L-dopa (50 mg/kg, s.c.), pargyline (100 mg/kg, i.p.), FLA-63 (10-20 mg/kg, s.c.) and FLA-63 (10 mg/kg, s.c.) plus L-dopa (50 mg/kg, s.c.) profoundly shortened the latency of seizures induced by chloroquine (65 mg/kg, i.p.). L-Dopa (50 mg/kg, s.c.) weakly reduced the latency and weakly increased the incidence of chloroquine (50 mg/kg, i.p.)-induced seizures. alpha-Methyl-p-tyrosine (25-100 mg/kg, i.p.) dose-dependently and significantly reduced the incidence and significantly prolonged the latency of chloroquine (65 mg/kg, i.p.)-induced seizures. However, L-dopa (50 mg/kg, s.c.) effectively increased the proportion of animals convulsing and effectively reduced the latency of seizures induced by chloroquine (65 mg/kg, i.p.) in alpha-methyl-p-tyrosine-pretreated mice. Haloperidol (0.25-1.0 mg/kg, i.p.) and pimozide (2-4 mg/kg, i.p.) markedly reduced the incidence and markedly prolonged the latency of seizures induced by chloroquine (65 mg/kg, i.p.) in a dose-related manner. However, apomorphine (0.4-0.8 mg/kg, s.c.) and L-dopa (25-50 mg/kg, s.c.) profoundly attenuated the protective effects of haloperidol (0.5 mg/kg, i.p.) and pimozide (4 mg/kg, i.p.) against chloroquine (65 mg/kg, i.p.)-induced seizures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chloroquine-induced seizures in mice: the role of monoaminergic mechanisms. 847 29

Methionine sulfoximine induces epileptiform convulsions in rats. A possible involvement of acetylcholine in the onset of convulsions was investigated. A subconvulsive dose of methionine sulfoximine increased the brain acetylcholine concentration. After administration of a convulsive dose, atropine neither prevented the onset of the seizures nor prevented the increase in acetylcholine concentration. Physostigmine enhanced the increase in acetylcholine level but did not modify the time course nor the intensity of the convulsions. L-DOPA suppressed the seizures without inhibiting the increase in acetylcholine level. The choline content decreased after the convulsant dose. The increase in acetylcholine content is therefore not the unique cause of the seizures, which could result from the reduction of striatal inhibition due to a decrease in dopamine level induced by methionine sulfoximine.
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PMID:Methionine sulfoximine increases acetylcholine level in the rat brain: no relation with epileptogenesis. 858 Apr 33

A selection of biphenyl-analogues of 2-amino-7-phosphonoheptanoic acid (AP7), N-methyl-D-aspartate (NMDA) receptor antagonists with high affinity in vivo efficacy. The lead compound SDZ EAB 515 was found to inhibit L-phenylalanine uptake by the large neutral amino acid carrier in vitro and in vivo; active transport may thus confer a good bioavailability to this class of compounds. CNS effects were demonstrated by significant changes in 2-deoxyglucose-uptake in various brain regions at doses from 1 to 10 mg/kg i.p. With the most active agent, SDZ 220-581, full protection against maximal electroshock seizures (MES) was obtained at oral doses of 10 mg/kg in rats and in mice. The compound had a fast onset (< or = 1 hr) and a long duration (> or = 24 hr) of action. Motor-debilitating effects (impairment of rotarod performance) occurred at doses about 10 times higher than those required for protection against MES. Neuroprotective activity was demonstrated by the ability of the compounds to reduce the extent of quinolinic acid-induced striatal lesions in rats, in the dose range of 3-15 mg/kg (i.p.) or 10-50 mg/kg (p.o.). In the middle cerebral artery occlusion (MCAO) model of focal cerebral ischemia in rats, the test compounds reduced the infarct size by 40-50% when given i.v. before or by 20-30% when given i.v. 1 hr after MCAO. SDZ 220-581 provided 20-30% protection at > or = 2 x 10 mg/kg p.o. This compound also showed analgesic activity at low oral doses in a model of neuropathic pain, although higher doses were required in model of mechanical inflammatory hyperalgesia. Unexpectedly, SDZ 220-581 at low s.c. doses counteracted the antiparkinsonian effects of L-DOPA in MPTP-treated marmosets. (Sub)chronic administration of SDZ 220-581 did not reduce its ability to protect against quinolinic acid neurotoxicity, and no upregulation of NMDA receptors was detected using a [3H]CGP-39653 binding assay. In conclusion, from a series of biphenyl-AP7-derivatives, SDZ 220-581 is clearly the most active compound in vivo. Its pharmacological profile with a good, long-lasting oral activity might open up novel therapeutic applications for competitive NMDA receptor antagonists.
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PMID:Biphenyl-derivatives of 2-amino-7-phosphono-heptanoic acid, a novel class of potent competitive N-methyl-D-aspartate receptor antagonists--II. Pharmacological characterization in vivo. 888 75

Niemann-Pick disease Type C (NPC) is a progressive neurovisceral metabolic disorder that is caused in most patients by a defect in a recently found gene, NPC-1. Neurological damage includes visual disorders such as vertical supranuclear gaze palsy, movement disorders such as dystonia and ataxia, dementia, and seizures. So far the biochemical deficit, most likely manifested by delayed intracellular cholesterol transport, has not been correlated with the progressive neurological damage. A mutant Balb/C mouse with a defect in the same gene is used as a model to study NPC. Pathological examination of brain tissue obtained by autopsy from NPC patients or brains of affected NPC mice of different ages, revealed signs of extensive damage throughout the brain, including neurofibrillary tangles and intracellular storage of various compounds. Loss of cerebellar Purkinje cells was the most significant specific damage. The present study examined whether the neurochemical changes present in the NPC mouse brain were related to the pathological changes. The results show major alterations in the levels of serotonin and its main metabolite, 5-hydroxyindoleacetic acid, in the cerebellum and cortex of NPC mice. The levels of the inhibitory amino acid glycine were threefold higher in the cerebellum of NPC mice and those of glutamate and GABA decreased in the cortex. Tyrosine hydroxylase immunoreactivity was present in Purkinje cells, and the levels of L-DOPA increased specifically in the vermis of the cerebellum. These results are the first to indicate changes in neurotransmitters in NPC and that these could be correlated with some of the neuropathology of this disease.
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PMID:Neurochemical alterations in the cerebellum of a murine model of Niemann-Pick type C disease. 967 2


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