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)

We have previously reported that L-deprenyl (selegiline), an irreversible inhibitor of monoamine oxidase type B (MAO-B), exerts anticonvulsant activity against different seizure types in mice and rats. The anticonvulsant effect of L-deprenyl was rapid in onset but short lasting, arguing in favor of other, reversible mechanisms of L-deprenyl as a basis for the anti-seizure activity. For further evaluation, we administered L-deprenyl continuously via subcutaneously implanted osmotic minipumps in mice and determined the threshold for myoclonic seizures induced by i.v. infusion of pentylenetetrazol repeatedly during prolonged treatment, with treatment periods lasting from 2 to 4 weeks. For comparison with continuous administration via minipumps, L-deprenyl was injected once daily at a dose (10 mg/kg) known to produce complete and irreversible inhibition of MAO-B and anticonvulsant effects after acute administration in rodents. Continuous administration of L-deprenyl, 50 or 100 mg/kg per day, led to a progressive increase in seizure threshold in the absence of any observable adverse effects, while administration of 10 mg/kg per day via minipumps was devoid of any significant anticonvulsant effect. When 10 mg/kg were administered once daily in the afternoon for 4 weeks and the seizure threshold was determined repeatedly in the morning, no significant anticonvulsant effect was observed. The data argue against a critical role of MAO-B inhibition in the anticonvulsant activity of L-deprenyl but suggest that other, reversible biochemical and cellular effects known to occur at higher doses of this drug are involved in this respect. In view of the short half-life of L-deprenyl, these reversible effects can only be maintained during chronic treatment when the drug is given continuously such as via implanted minipumps.
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PMID:Anticonvulsant efficacy of L-deprenyl (selegiline) during chronic treatment in mice: continuous versus discontinuous administration. 988 81

A growing number of Americans are using herbal products for preventive and therapeutic purposes. The manufacturers of these products are not required to submit proof of safety and efficacy to the U.S. Food and Drug Administration before marketing. For this reason, the adverse effects and drug interactions associated with herbal remedies are largely unknown. Ginkgo biloba extract, advertised as improving cognitive functioning, has been reported to cause spontaneous bleeding, and it may interact with anticoagulants and antiplatelet agents. St. John's wort, promoted as a treatment for depression, may have monoamine oxidase-inhibiting effects or may cause increased levels of serotonin, dopamine and norepinephrine. Although St. John's wort probably does not interact with foods that contain tyramine, it should not be used with prescription antidepressants. Ephedrine-containing herbal products have been associated with adverse cardiovascular events, seizures and even death. Ginseng, widely used for its purported physical and mental effects, is generally well tolerated, but it has been implicated as a cause of decreased response to warfarin. Physicians must be alert for adverse effects and drug interactions associated with herbal remedies, and they should ask all patients about the use of these products.
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PMID:Herbal remedies: adverse effects and drug interactions. 1053 82

Investigations with specific PET ligands that bind to specific neuro-receptors give information on abnormalities of neurotransmission involved in the pathophysiology of the epilepsies. Data need to be interpreted in the light of optimal structural imaging. Objective voxel-based and region-based analyses, with correction of partial volume effect, are complementary. Central benzodiazepine (cBZR) and opioid receptors have been studied most. Reduced cBZR binding is commonly seen at an epileptic focus, in a more restricted distribution than an area of hypometabolism, and sometimes also in projection areas. In contrast to acquired lesions causing partial seizures, focal increases in cBZR binding have been demonstrated in malformations of cortical development and also in areas of brain that appear normal on MRI, indicating the widespread nature of the abnormalities. Focal abnormalities of cBZR are also commonly found in patients with partial seizures and normal MRI. It is not yet clear how useful these data will prove to be in presurgical evaluation. Mu- and delta-opioid receptors have been found to be increased in temporal neocortex overlying mesial temporal epileptic foci, but with different patterns of increase. Dynamic studies of the binding of 11C-diprenorphine to opioid receptors are possible using PET, and have implied the release of cerebral endogenous opioids at the time of serial absences and reflex seizures induced by reading. Other tracers, that have been applied less widely, label the enzyme monoamine oxidase type B and peripheral benzodiazepine and histamine H1 receptors.
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PMID:Positron emission tomography receptor studies in epilepsy. 1047 64

Isatin (indole-2,3-dione) has been found in mammalian tissues as one of major components of tribulin, a postulated endogenous marker of stress and anxiety. I previously identified isatin as an endogenous inhibitor of monoamine oxidase (MAO) in the human urine and the brain of stroke-prone spontaneously hypertensive rats (SHRSP) using GC-MS. A single dose of isatin significantly increased norepinephrine (NE) and 5-hydroxytryptamine (5-HT) concentrations measured 2 h later in the various brain regions of normotensive Wistar Kyoto rats (WKY). Striatal acetylcholine (ACh) and dopamine (DA) levels significantly increased 2 h after the administration of isatin. Perfused through a microdialysis probe, isatin also produced a significant and concentration-dependent increase in the ACh and DA concentration in the perfusate from the rat striatum. In the patients with Parkinson's disease, urinary isatin concentrations tended to increase according to the severity of disease, as classified by the Hoehn and Yahr criteria. Isatin significantly increased striatal DA levels in a rat model of Parkinson's disease. Isatin may play a role in the regulation of the brain levels of ACh and DA. Furthermore, isatin has a wide spectrum of biological properties: (a) a marker of stress and anxiety, (b) an inhibitor of a number of enzymes, (c) an anti-seizure agent, (d) an inhibitor of benzodiazepin receptors and ANP binding to its receptors.
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PMID:[Pharmacological role of isatin, an endogenous MAO inhibitor]. 1077 57

Psychiatry as a field was transformed by the discovery and introduction of electroconvulsive therapy (ECT) as a treatment in the early part of this century. ECT demonstrated that depression was a disease of the brain and that it could be treated with a direct brain intervention. Psychiatry's evolution continued in 1958 with the discovery of the antidepressant activity of the monoamine oxidase inhibitors. Interestingly, although the area of neuropsychopharmacology has continued to advance, the realm of physical somatic interventions in psychiatry has lagged behind. With perhaps the exception of light therapy, there were no advances in somatic interventions in psychiatry. However, in 1985, Barker et al. developed a brief high intensity electromagnet capable of depolarizing cortical neurons, called transcranial magnetic stimulation (TMS). There has been much interest in the past 10 years in whether TMS might have antidepressant actions, similar to ECT but without causing a seizure and with no apparent cognitive side effects. This review examines the basic principles underlying TMS, and describes how TMS differs from electrical stimulation and the other uses of magnets.
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PMID:Improvement of depression following transcranial magnetic stimulation. 1112 13

Citalopram is a member of the selective serotonin reuptake inhibitor class of antidepressants. In 1998, citalopram was approved by the US Food and Drug Administration for the treatment of major depression. Like the other selective serotonin reuptake inhibitors, citalopram enjoys a relatively benign side effect profile compared with the tricyclic antidepressants and the monoamine oxidase inhibitors. However, citalopram has been associated with electrocardiographic changes and seizures at doses greater than 600 mg per day. Fatalities have occurred with citalopram-only overdoses. We report the case of a healthy 21-year-old woman who developed QTc interval prolongation after ingestion of approximately 400 mg citalopram. We discuss the cardiac effects of citalopram, review previous cases of citalopram overdose, and discuss treatment recommendations.
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PMID:QTc interval prolongation associated with citalopram overdose: a case report and literature review. 1139 Nov 27

Progesterone receptors are found in many of the same brain areas as estrogen receptors, including the hypothalamus and limbic system. The limbic system, particularly the amygdala, plays a prominent role in regulating emotion and mood. Progestogens decrease brain excitability, whereas estrogens increase it. This explains, in part, why women with epilepsy have a higher frequency of seizures during the late follicular and ovulatory phases of the menstrual cycle than during the luteal phase. In addition, progesterone has been shown to have profound anesthetic properties and to increase the concentration of monoamine oxidase (MAO), the enzyme that catabolizes serotonin in the brain), whereas estrogen decreases MAO, thereby increasing the concentration of serotonin. The purpose of this paper is to review the extant research regarding these biologic effects of progestogens on brain function.
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PMID:Progestogens used in menopause. Side effects, mood and quality of life. 1139 37

Acute hyperammonemia resulting from congenital urea cycle disorders, Reye syndrome or acute liver failure results in severe neuronal dysfunction, seizures and death. Increasing evidence suggests that acute hyperammonemia results in alterations of mitochondrial and cellular energy function resulting from ammonia-induced inhibition of the tricarboxylic acid cycle enzyme alpha-ketoglutarate dehydrogenase and by activation of the NMDA receptor. Antagonists of this receptor and NOS inhibitors prevent acute ammonia-induced seizures and mortality and prevent acute ammonia-induced changes in mitochondrial calcium homeostasis and cellular energy metabolism. Acute hyperammonemia also results in decreased activities of free radical scavenging enzymes and again, free radical formation due to ammonia exposure is prevented by either NMDA receptor antagonists or NOS inhibitors. Acute hyperammonemia also results in activation of "peripheral-type" benzodiazepine receptors and monoamine oxidase-B, enzymes which are localized on the mitochondrial membranes of astrocytes in the CNS. Activation of these receptors results in mitochondrial swelling and in increased degradation of monoamines, respectively. Alterations of mitochondrial function could contribute to the neuronal dysfunction characteristic of acute hyperammonemic syndromes.
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PMID:Mitochondrial dysfunction in acute hyperammonemia. 1185 Jan 5

The current literature on the interaction between antidepressant drugs and electroconvulsive therapy (ECT) is reviewed. Tricyclic antidepressants, atypical antidepressants, and monoamine oxidase inhibitors are discussed. The efficacy of combinations and possible adverse effects (mainly cardiovascular and seizure threshold effects) are considered. Many previous studies on the efficacy of combinations used inadequate methods, and the safety data consist largely of anecdotes and small case series. Additional studies are needed to assess the safety and efficacy of the combined use of antidepressants and ECT.
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PMID:Combined ECT and Antidepressant Drug Therapy. 1194 Dec 21

Despite many predictions that electroconvulsive therapy (ECT) would be replaced by pharmacotherapy, ECT has remained an invaluable adjunct in the management of severe psychiatric disease. Both pharmacotherapy and ECT continue to be used extensively, and will frequently be administered concurrently. The majority of patients requiring ECT will need anaesthesia; therefore, interactions could conceivably occur between the psychotropic drugs, ECT and the anaesthetic agents utilised. In managing an anaesthetic for ECT the effects of the anaesthetic agents and other medications on seizure intensity are important determinants influencing outcome. With regard to the antidepressants, tricyclic antidepressants (TCAs) and ECT can be combined safely and beneficially. More care is required when ECT is administered in the setting of a monoamine oxidase inhibitor (MAOI), especially the older irreversible varieties and in patients recently placed on MAOI therapy. Of the anticonvulsants and mood stabilisers, lithium and ECT given concurrently add significant risk of delirium and/or organic syndromes developing. Possible concerns with valproate, carbamazepine, lamotrigine, gabapentin and topiramate are that they may inhibit seizure activity. Additionally, carbamazepine may prolong the action of suxamethonium (succinylcholine). The combination of antipsychotics and ECT is well tolerated, and may in fact be beneficial. As regards the anxiolytics, benzodiazepines have anticonvulsant properties that might interfere with the therapeutic efficacy of ECT. CNS stimulants on the other hand may prolong seizures as well as produce dysrhythmias and elevate blood pressure. Calcium channel antagonists should be used with great care to avoid significant cardiovascular depression. The anaesthesiologist should therefore remain vigilant at all times, as untoward responses during ECT might occur suddenly due to interactions between psychotropics, anaesthetic agents and/or ECT.
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PMID:Interactions between psychotropics, anaesthetics and electroconvulsive therapy: implications for drug choice and patient management. 1194 7


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