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)

L-Huperzine-A (Hup-A), a natural cholinesterase inhibitor (ChEI) derived from the Chinese herb Huperzia serrata, was administered systemically (i.p.) or locally through the microdialysis probe into the rat cortex. Systemic Hup-A significantly increased acetylcholine (ACh) levels above baseline at doses of 0.1, 0.3, and 0.5 mg/kg; the increases were 54%, 129%, and 220%, respectively. Norepinephrine (NE) and dopamine (DA) levels were also increased 121% and 129% above baseline at 0.3 mg/kg, and 143% and 153% at 0.5 mg/kg. Peak cholinesterase (ChE) inhibition was 23% at 60 min with the 0.3 mg/kg dose. Huperzine-A, perfused through the microdialysis probe, produced a maximal increase of ACh levels of 3090% and 7790% at concentrations of 5 and 50 microM. The ACh increase seen at both concentrations lasted at least 6 hr. At the 5-microM dose, NE and DA were increased by 214% and 386%; at the 50-microM dose, NE and DA were increased by 216% and 1141%. There were no changes of 5-HT levels. With local administration (via the probe), both doses produced facial-forelimb seizures that lasted throughout the perfusion. Our results show that Hup-A is a potent inhibitor of ChE which penetrates into the brain and produces a dose-dependent increase of ACh, NE, and DA in rat cortex. This effect is seen with both systemic and local intracerebral administration, suggesting cortical as well as subcortical effects of the drug.
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PMID:Second generation cholinesterase inhibitors: effect of (L)-huperzine-A on cortical biogenic amines. 750 Mar 84

Systemically administered (-)nicotine (0.2-1.2 mg/kg, s.c.) significantly increased the release of acetylcholine (ACh), norepinephrine (NE) and dopamine (DA) in rat cortex. The lowest dose of (-)nicotine examined (0.2 mg/kg, s.c.) also significantly elevated extracellular serotonin (5-HT) levels, and the maximal increases of extracellular ACh (122% at 90 min post injection) and DA levels (249% at 120 min post-injection) were observed following this dose. In contrast, the maximal increase of NE release (157% at 30 min post-injection) was observed following the highest dose of (-)nicotine injected (1.2 mg/kg, s.c.). This higher dose consistently produced generalized seizures. Repeating the (-)nicotine (0.58 mg/kg, s.c.) injection four hours after the first administration significantly elevated extracellular NE levels and also appeared to increase DA and ACh release. In addition, extracellular ACh and DA levels increased significantly in the dialysate after (-)nicotine was administered directly to the neocortex through the microdialysis probe membrane. Norepinephrine levels appeared to be elevated in the cortex following local administration as well.
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PMID:Effects of local and repeated systemic administration of (-)nicotine on extracellular levels of acetylcholine, norepinephrine, dopamine, and serotonin in rat cortex. 756 73

L-Deprenyl (selegiline) is an irreversible inhibitor of monoamine oxidase type B, but also exerts several effects on dopamine and noradrenaline systems independent of monoamine oxidase type B inhibition. Thanks to these properties, L-deprenyl has gained wide acceptance in the therapy of Parkinson's disease by using L-deprenyl both with levodopa and alone. Furthermore, L-deprenyl improves the performance of patients with Alzheimer's disease. Epilepsy, particularly temporal lobe epilepsy with complex-partial seizures, is often associated with disturbances of cognitive function and behavior, and it has been suggested that a drug combining cognition-enhancing and antiepileptic activity would be of benefit in the treatment of epileptic patients. This prompted us to study if L-deprenyl exerts anticonvulsant efficacy in amygdala-kindled rats, i.e., a useful model of complex-partial seizures in humans. In addition to anticonvulsant activity, i.e., effects on already developed seizures, we determined whether L-deprenyl exhibits antiepileptogenic properties, i.e., suppressive effects on development of kindling. In all experiments, behavioral alterations of the rats in response to L-deprenyl were monitored closely. In order to assess the role of active metabolites in the anticonvulsant and behavioral effects of L-deprenyl in the kindling model, the D-enantiomer of deprenyl, which is metabolized to more potent compounds (D-amphetamine and D-methamphetamine) than the L-enantiomer, was used for comparison. In fully kindled rats, L-deprenyl potently increased the threshold for focal afterdischarges. The most marked increase in afterdischarge threshold (up to 250% above control) was seen after a dose of 10 mg/kg, whereas the D-enantiomer was ineffective at this dosage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anticonvulsant and antiepileptogenic effect of L-deprenyl (selegiline) in the kindling model of epilepsy. 761 14

Noradrenergic neurons are thought to be involved in the process of seizure development and long-term central nervous system plasticity associated with kindling and epilepsy. These processes involve actions of noradrenaline at alpha 1-, alpha 2- and beta 1-adrenergic receptors. In this study, quantitative in vitro autoradiography was used to investigate possible changes in the density of brain alpha 1-adrenergic receptors in a kindling model of epilepsy in the rat. Kindling was produced by daily unilateral stimulation of the amygdala. The alpha 1A+alpha 1B subtypes of adrenergic receptors were labelled with the alpha 1-selective antagonist, [3H]prazosin and alpha 1B receptors, detected in the presence of 10 nM WB4101 to selectively occupy alpha 1A receptors, accounted for 50% of total alpha 1 receptors in cerebral cortex. Autoradiographic studies identified significant and long-lasting, ipsilateral increases in specific [3H]prazosin binding throughout layers I-III of the cortex in sham-operated, unstimulated rats, presumably caused by the surgical implantation of the stimulating electrode within the basolateral amygdaloid nucleus. Binding to alpha 1A + alpha 1B receptors and alpha 1B receptors was increased by an average of 35 and 60%, respectively under these conditions. Stimulation-evoked seizures produced dramatic bilateral increases in specific [3H]prazosin binding to alpha 1A + alpha 1B receptors and particularly to alpha 1B receptors in layers I-III of all cortical areas examined. These changes were rapidly induced and the largest increases (range alpha 1A + alpha 1B 80-340%; alpha 1B 165-380%) occurred at 0.5-2 h after the last stage 5 kindled seizure. At 1 and 3 days after the last seizure, increases were measured for both alpha 1A + alpha 1B and alpha 1B receptors in layers I-III of particular cortical regions, but not overall (e.g. 60-210% increase in perirhinal cortex at both times, with increases also in retrosplenial, hindlimb, occipital, parietal and temporal cortices). Between 2-8 wk post-stimulation specific receptor binding levels were equivalent to those in sham-operated, unstimulated rats. In contrast to the large and widespread increases in outer cortical [3H]prazosin binding, smaller increases were detected in the inner cortex (layer V-VI) at individual times (65-75% increase at 30 min), while no significant changes occurred in several other brain regions examined, including thalamus, which contained a high density of alpha 1A and alpha 1B receptors, or hippocampus which has a low density of both alpha 1 receptor subtypes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Spatiotemporal alterations of central alpha 1-adrenergic receptor binding sites following amygdaloid kindling seizures in the rat: autoradiographic studies using [3H]prazosin. 774 43

Convulsive seizures were elicited by a single unilateral microinjection of the cholinergic muscarinic agonist, carbachol, into the thalamus. Moreover, using systematic single microinjections of carbachol, we identified specific regions within the thalamus which were the origin of behavioural and electrocortical correlates associated with limbic and/or generalized convulsive seizures. Neither serotonin, noradrenaline nor glutamate had any convulsive effect when injected into the epileptogenic thalamic areas. The specific epileptogenic sites identified within the thalamus may provide a new experimental model which should prove useful for exploring the thalamic and thalamo-cortical mechanisms underlying limbic and generalized convulsive seizure disorders.
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PMID:Limbic and/or generalized convulsive seizures elicited by specific sites in the thalamus. 776 56

The thresholds for pentylenetetrazol and lidocaine-induced clonic convulsions were significantly influenced by manipulation of brain biogenic amines. Pretreatment with inhibitors of monoamine synthesis, alpha-methyl-p-tyrosine and p-chlorophenylalanine, caused significant decreases in brain monoamine contents and pentylenetetrazol seizure threshold, while the threshold for lidocaine-induced convulsions was significantly increased by either treatment. Moreover, the inhibitor of dopamine-beta-hydroxylase, disulfiram, caused significant decrease in brain noradrenaline (NA) and significant increase in brain dopamine (DA) contents. The threshold for pentylenetetrazol-induced convulsions was decreased by treatment with disulfiram, while that of lidocaine was increased by the same treatment. Furthermore, treatment with L-dihydroxyphenylalanine (L-DOPA) caused significant increase in brain DA contents, while 5-hydroxytryptophan (5-HTP) treatment caused significant increase in brain 5-hydroxytryptamine (5-HT) contents, but the thresholds for lidocaine and pentylenetetrazol-induced convulsions were not influenced by either treatment. These results may suggest that the brain monoaminergic systems, different from their ability to inhibit control of pentylenetetrazol seizures, act to potentiate lidocaine-induced convulsions.
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PMID:Alterations of lidocaine and pentylenetetrazol-induced convulsions by manipulation of brain monoamines. 780 Jun 57

The time course and extent of changes in plasma prolactin, noradrenaline, vasopressin and oxytocin levels is reported following serial observations of a prolonged epileptic seizure arising in the temporal lobe, recorded by video-EEG-telemetry, in which the epileptic activity evolved from a simple partial to complex partial to secondarily generalised attack. The prolactin levels were markedly elevated during the phase of the simple partial seizure, at a time when consciousness was preserved, when motor activity was minimal and when EEG activity was highly localised. The hormonal levels continued to rise during the subsequent seizure evolution, suggesting that the duration (or intensity) of the seizure is an important, perhaps the most important, factor determining the degree of prolactin release during limbic seizures. Indeed, the prolactin elevation in this case (26 times the baseline level) is higher than any previously recorded, reflecting the unusual duration and intensity of this seizure. We did not observe the phenomenon of "exhaustion" of prolactin release and levels peaked after 49 min, and were high for over 2 h after the onset of the seizure, and after the convulsion had ceased. The concentrations of vasopressin, oxytocin and noradrenaline remained low during the aura, but rapidly increased during the phase of generalisation. The oxytocin and noradrenaline levels peaked during the phase of generalised convulsion, but the vasopressin levels peaked well into the post ictal phase, and remained high for several hours.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma concentrations of prolactin, noradrenaline, vasopressin and oxytocin during and after a prolonged epileptic seizure. 780 41

Gamma-aminobutyric acid (GABA)-releasing polymer matrices were implanted bilaterally, immediately dorsal to the substantia nigra, in rats previously kindled in the amygdala. Two days after implantation, rats with GABA-releasing matrices exhibited only focal limbic seizures in response to electrical stimulation, whereas animals with control matrices devoid of GABA had generalized convulsions. GABA release from the polymer matrices was high during the first days after implantation, as demonstrated both in vitro and, using microdialysis, in vivo. The anticonvulsant effect was no longer observed at 7 and 14 days at which time GABA release was found to be low. In a parallel experiment, polymer matrices containing noradrenaline (NA) were implanted bilaterally into the hippocampus of rats with extensive forebrain NA depletion induced by an intraventricular 6-hydroxydopamine injection. No effect on the development of hippocampal kindling was observed, despite extracellular NA levels exceeding those of rats with intrahippocampal locus coeruleus grafts that have previously been shown to retard kindling rate. The results indicate that GABA-releasing implants located in the substantia nigra region can suppress seizure generalization in epilepsy, even in the absence of synapse formation and integration with the host brain. In contrast, the failure of NA-releasing polymer matrices to retard the development of seizures in NA-depleted rats suggests that such an effect can only be exerted by grafts acting through a well-regulated, synaptic release of NA.
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PMID:Seizure suppression in kindling epilepsy by intracerebral implants of GABA- but not by noradrenaline-releasing polymer matrices. 781 77

Solid pieces of fetal locus coeruleus (LC) or superior cervical ganglion (SCG) were placed into a fimbria-fornix lesion cavity in 6-hydroxydopamine-treated, noradrenaline (NA)-denervated rats. Six to 8 months later, all animals were subjected to electrical kindling stimulations in the hippocampus until they had reached the fully kindled state. Nongrafted lesioned animals showed markedly increased kindling rate which was partly attenuated by LC but not SCG grafts. In both LC- and SCG-grafted animals, dopamine beta-hydroxylase immunocytochemistry demonstrated a high density of graft-derived noradrenergic fibers in the dorsal hippocampus, whereas reinnervation of the ventral hippocampus was much more sparse. Subregional distribution of these fibers within the hippocampus was different in the two grafted groups. Both grafts partly restored basal extracellular NA levels in the hippocampus and reacted to generalized seizures by a significant (two- to threefold) increase of NA release, as measured by intracerebral microdialysis. Our data indicate (i) that seizure activity can regulate transmitter release from noradrenergic neurons in both LC and SCG grafts, (ii) that only fetal LC grafts retard seizure development in kindling, and (iii) that the inability of SCG implants to influence kindling epileptogenesis could be due to a lack of synaptic contacts between the graft-derived ganglionic fibers and host hippocampal neurons.
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PMID:Seizure development and noradrenaline release in kindling epilepsy after noradrenergic reinnervation of the subcortically deafferented hippocampus by superior cervical ganglion or fetal locus coeruleus grafts. 786 65

Ketotifen produced seizures in a 5-year-old boy with secondary generalized epilepsy (SGE) and allergic rhinitis. To confirm that the seizures were due to histamine H1 receptors blockade, d-chlorpheniramine was administered with monitoring electroencephalography (EEG). Administration of d-chlorpheniramine significantly increased the number of epileptic discharges in the patient, compared with those before administration. Plasma noradrenaline and dopamine levels were not affected by treatment with d-chlorpheniramine. These findings indicate that histamine H1 receptors blockade produced convulsions and increased epileptic discharges on EEG. Recently, several experimental reports have shown that histamine has an inhibitory role on convulsions through histamine H1 receptors. Experimental findings and present results show that histamine H1 antagonists have proconvulsant effects, especially in the developmental period. Thus, it is recommended that centrally-acting histamine H1 antagonists should be avoided in epileptic patients, especially in children of pre-school age.
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PMID:Proconvulsant effect of ketotifen, a histamine H1 antagonist, confirmed by the use of d-chlorpheniramine with monitoring electroencephalography. 810 Dec 46


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