Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nine 5-(3,4,5-trimethoxyphenyl)-4-substituted aryl-3-hydrazinocarbonylmethylthio-4H-1,2,4-triazoles were investigated for their anticonvulsant and monoamine oxidase inhibitory properties. The protection afforded by these compounds at a dose of 100 mg/kg ranged from 20-90% against pentylenetetrazol-induced seizures and 20-40% against electric shock-induced convulsions. The degree of in vitro monoamine oxidase inhibition by substituted triazoles ranged from 41-80%, 18-36% and 20-40% using kynuramine, tyramine and 5-hydroxytryptamine as substrate, respectively. The approximate LD50 values of greater than 1000 mg/kg exhibited low toxicity of substituted triazoles.
 ...
PMID:Anticonvulsant activity and monoamine oxidase inhibitory properties of substituted 1,2,4-triazoles. 717 60

Monoamine oxidase inhibitory and anticonvulsant properties of 2-substituted styryl-6-bromo-3-(4-ethylbenzoate/4 benzhydrazide)-4-quinazoles are studied. All styryl quinazolone esters except compound number 9 exhibited monoamine oxidase inhibitory properties during oxidative deamination of kynuramine. Corresponding hydrazides were found to have relatively higher activity. All these quinazolones were able to protect against pentylenetetrazol induced seizures. These observations in general do not prove that monoamine oxidase inhibitory properties represent the biochemical basis for the anticonvulsant activity of these compounds.
 ...
PMID:Correlation between monoamine oxidase inhibitors and anticonvulsants. 742 Apr 38

The specific acitivity of cerebral histamine N-methyltransferase (HMT) was significantly lower in the audiogenic seizure-susceptible (SS) 21-day old DBA/2J mouse when compared to the non-susceptible 70-day old DBA/2J mouse but not when compared to the seizure resistant (SR) C57B1/6J mouse at 21 days of age. There was no significant difference between the two strains at 70 days of age. The lower HMT specific activity was also observed in a SS mutant of the deermouse Peromyuscus maniculatus, relative to the SR, wild-type animal. The activity of cerebral catechol-O-methyltransferase (COMT) was significantly lower in the DBA/2J mice relative to the C57B1/6J at 21 and 70 days while, in Peromyscus, it was higher in the SS mutant than in the SR animal. The activity of MAO, B was lower in the 21-day old, relative to the 70-day old DBA/2J and the 21-day old C57B1/6J mice. There were no differences in MAO A or B between SS and SR Peromyscus. The findings raise the possibility that cerebral methylation may operate at characteristic rates in SS animals.
 ...
PMID:Differences in activity in cerebral methyltransferases and monoamine oxidases between audiogenic seizure susceptible and resistant mice and deermice. 743 89

The temporal profiles of aminergic neurotransmitter levels and of their acid metabolites after transient global cerebral ischemia in awake rats with and without subsequent seizures were compared using a microdialysis approach. In seizure animals, the post-ischemic levels of dopamine and serotonin were higher than the levels observed in the non-seizure controls. Inversely, the levels of the three neurotransmitter metabolites increased rapidly in the controls but not in seizure animals, where they remained at the low levels observed during and immediately after ischemia. This particular pattern is similar to that observed in rats submitted to prolonged ischemia or pretreated with monoamine oxidase inhibitors. In the seizure animals, neurotransmitter metabolites remained at low levels, as if the hypoxia had continued after the period of ischemia, inhibiting monoamine oxidase activity and, perhaps, neurotransmitter recapture.
 ...
PMID:Temporal profile of aminergic neurotransmitter release in striatal dialysates in rats with post-ischemic seizures. 751 44

The present study examines the influence of electroconvulsive seizure (ECS), as well as several antidepressant drug treatments, on the induction of c-fos mRNA in response to acute restraint stress. Acute (45-minute) restraint stress resulted in five- to sixfold elevation of c-fos mRNA levels in rat frontal cortex. Chronic administration of ECS significantly decreased the induction of c-fos mRNA levels in response to acute restraint stress, and this effect was observed after chronic (6 to 9 days) but not acute (1 or 3 days) of ECS treatment. In addition, c-fos induction in response to acute restraint stress was down-regulated by chronic, but not acute, administration of tranylcypromine or imipramine, two drugs that nonselectively increase synaptic levels of norepinephrine and serotonin by inhibition of monoamine oxidase or neurotransmitter reuptake, respectively. Moreover, chronic administration of desipramine or sertraline, selective re-uptake inhibitors of norepinephrine, or serotonin, respectively, also significantly down-regulated the induction of c-fos mRNA in response to restraint stress. Chronic administration of ECS, tranylcypromine, or imipramine also decreased stressed-induced levels of NGFI-A mRNA, another immediate early gene transcription factor, whereas levels of c-jun mRNA were not influenced by either stress or antidepressant treatments. The results demonstrate that chronic, but not acute, administration of ECS and several different classes of antidepressant drugs down-regulates stress-induced levels of c-fos mRNA, suggesting that this effect may be a common, postreceptor action of antidepressant treatments.
 ...
PMID:Chronic antidepressant treatment down-regulates the induction of c-fos mRNA in response to acute stress in rat frontal cortex. 761 55

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)
 ...
PMID:Anticonvulsant and antiepileptogenic effect of L-deprenyl (selegiline) in the kindling model of epilepsy. 761 14

Monoamine neurotransmitters are important in the development of the immature mammalian brain, prior to assuming their role as neurotransmitters. The endogenous levels of these transmitters are highly regulated by the enzyme monoamine oxidase (MAO). Thus, any change in this enzyme should have a profound effect on brain development. In order to test this hypothesis, we treated developing rat pups with the monoamine oxidase inhibitors (MAO-Is), clorgyline (MAO-A, 3 mg/kg), and deprenyl (MAO-B, 3 mg/kg) throughout gestation (MAO-I-birth), or throughout gestation and to sacrifice (MAO-I-sac). The animals were analyzed for serotonin and dopamine terminal density, using 3H-paroxetine and 3H-GBR 12935, respectively. Whereas there were no changes in the development of the dopamine system, the serotonin system was severely affected, particularly in the cortex that showed a significant reduction of innervation at 30 days postnatal. The animals reached all normal development milestones on schedule, and had no changes in measures of anxiety (% light/dark); however, the animals showed increased open field activity and deficits in a passive avoidance paradigm, which may be a measure of impulsivity. The MAO-I-sac animals were severely impaired, showing stereotypic behavior, seizures, and eventually visual impairments. Our results are discussed in terms of relevance to human disease states, such as atypical Norrie's disease, impulsivity, and hyperactivity. As well, our results should be used to caution against the use of MAO-Is in women of child-bearing age.
 ...
PMID:Effects of gestational exposure to monoamine oxidase inhibitors in rats: preliminary behavioral and neurochemical studies. 784 Aug 64

Major depression is a common and disabling disorder with far-reaching social and economic implications. Nonetheless, major depression is treatable by one of the many currently available antidepressants with response rates of approximately 65-70%. Treatment of depression has improved in recent years because of the availability of effective and well-tolerated antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs). The currently available antidepressants are generally equally effective and are distinguished primarily by side-effect profiles. The side effects of tricyclic antidepressants (TCAs) are attributed to their nonspecific interaction with cholinergic, histaminergic, serotonergic, and dopaminergic receptors in the central nervous system. The secondary amine TCAs, nortriptyline and desipramine, are preferred among the TCAs because of a more favorable side-effect profile. The TCAs are cardiotoxic, and overdoses are frequently fatal. Adverse effects, including potentially fatal drug and food interactions, limit the use of the monoamine oxidase inhibitors (MAOIs); however, these agents have a role in the treatment of depression with comorbid anxiety, refractory depression, atypical depression, and bulimia. The SSRIs possess a class side-effect profile of headache, nausea, and sexual dysfunction. Individual differences in side effects may distinguish fluoxetine (nervousness, restlessness), sertraline (diarrhea, loose stools), and paroxetine (dry mouth). The SSRIs all inhibit certain cytochrome P450 isoenzymes involved in the metabolism of drugs, such as the TCAs, and each SSRI has been reported to increase plasma concentrations of concomitantly administered TCAs. Bupropion therapy is associated with a risk of seizure development, which can be minimized by multiple daily doses. Trazodone is sedating and can rarely cause priapism. The related compound, nefazodone, does not cause sexual dysfunction or priapism, but is associated with sedation. Venlafaxine, a recently available antidepressant that appears to have efficacy in treatment-refractory depression, may cause nausea that requires gradual upward dosage titration. Higher doses of venlafaxine may also cause elevations in blood pressure, heart rate, and serum cholesterol. As more is learned about the pathophysiology of depression, even more specific and well-tolerated antidepressants will be developed.
 ...
PMID:Contemporary management of depression. 799 23

Psychiatric medications cause side effects in several organ systems that need emergency evaluation and treatment. Serious cardiovascular side effects include postural hypotension, cardiac conduction blockade, and SA mode dysfunction; serious neurological side effects include extrapyramidal reactions, seizures, delirium, catatonia, pseudotumor cerebri, ataxia, and glaucoma; serious genitourinary side effects include urinary retention, nephrotic syndrome, and priapism, and the serious hematological side effect of agranulocytosis. Also potentially fatal syndromes secondary to psychiatric drugs are the neuroleptic malignant syndrome, hyperandrenergic crisis, the serotonin syndrome, and lithium toxicity. Individual psychiatric drug classes most notorious for causing side effects with high morbidity and mortality are low potency neuroleptics, clozapine, tertiary tricyclics, monoamine oxidase inhibitors, and lithium.
 ...
PMID:Emergencies caused by side effects of psychiatric medications. 816 98

CNS oxygen (O2) toxicity is complex, and the etiology of its most severe manifestation, O2 convulsions, is yet to be determined. A role for depletion of the brain GABA pool has been proposed, although recent data have implicated production of reactive O2 species, e.g. H2O2, in this process. We hypothesized that the production of H2O2 and NH3 produced by monoamine oxidase (MAO) would lead to depletion of GABA and production of nitric oxide (NO.) respectively, and thereby enhance CNS O2 toxicity. In this study, rats treated with an MAO inhibitor (pargyline) or a nitric oxide synthase inhibitor (LNNA) were protected against O2-induced convulsions. Selected cerebral amino acids including arginine were measured in control and O2 treated rats (6 ATA, 20 min) with or without drug pretreatment. After O2 exposure, the cerebral pools of glutamate, aspartate, and GABA decreased significantly while glutamine content increased relative to control (P < 0.05). After treatment with either enzyme inhibitor, glutamine, glutamate and aspartate concentrations were maintained near control levels. Remarkably, GABA depletion by O2 was not prevented despite protection from seizures by both pargyline and LNNA. The NO. precursor, arginine, was increased significantly in the brain by toxic O2 exposure, but both pargyline and LNNA inhibited this effect. Simultaneous norepinephrine measurements indicated that its storage substantially decreased during hyperoxia (P < 0.05), but this effect too was blocked by either pargyline or LNNA. These data indicate that protection against O2 by these inhibitors is not related to preservation of the GABA pool. More importantly, O2 dependent norepinephrine metabolism and NO. synthesis appear to be interactive during CNS O2 toxicity.
 ...
PMID:Cerebral amino acid, norepinephrine and nitric oxide metabolism in CNS oxygen toxicity. 846 4


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>