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)

In rats, intraventricularly injected antimelatonin antibody caused the appearance of transitory epileptiform abnormalities. Epileptic activity arose from and was limited to the cortical mantle of the hemisphere ipsilateral to the injection side. The occasional occurrence of lateralized seizures has also been observed. Control injection of saline, of the vehicle (rabbit serum), or of antibody saturated with melatonin induced flattening and desynchronization of the electroencephalogram but not epileptiform activity. Repeated antimelatonin injections caused reappearance of the same type of epileptic abnormalities that lasted slightly longer than the first time. Melatonin may play an inhibitory role in neuronal excitability.
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PMID:Epileptogenic action of intraventricularly injected antimelatonin antibody. 55 66

Melatonin, a hormone from the pineal gland, was tested for its anticonvulsant effects in male gerbils. Daily administration of melatonin (25 micrograms injection-1, s.c.) for ten weeks reduced the number and severity of seizures (total convulsion score: 7.67 +/- 1.83 in controls vs 2.47 +/- 0.90 in melatonin-injected animals, p < 0.05) associated with the injection of the convulsant, pentylenetetrazol (PTZ, 60 mg kg-1, s.c.). However, neither 12 weeks of short photoperiod exposure (LD 10:14) nor biweekly administration of melatonin pellets altered PTZ-induced convulsions. Overall, melatonin-injected gerbils were better able to survive and respond to seizures than control animals. No melatonin-injected gerbils died during seizure induction (0/31) while 5 out of 33 control gerbils died after PTZ injection. The mechanism for melatonin's anticonvulsant effects could be due to a direct inhibitory action on neural activity or a conversion of melatonin to an anticonvulsant compound that resembles the kynurenines.
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PMID:Novel anticonvulsant action of chronic melatonin in gerbils. 149 30

The objective of the present study was to assess whether the anticonvulsant activity of melatonin displays diurnal variability in hamsters. Convulsions were induced by administering 3-mercaptopropionic acid (3-MP). There was a significant diurnal variation in 3-MP-induced convulsions, hamsters being more prone to exhibit seizures during the night than during the day. Melatonin (50 mg/kg i.p.) had a maximal anticonvulsive effect in the early evening (20:00 h). The administration at 20:00 h of the central-type benzodiazepine antagonist, Ro 15-1788, although unable by itself to modify seizure threshold, blunted the anticonvulsant response to melatonin. The results indicate that the time-dependent anticonvulsant activity of melatonin is sensitive to central-type benzodiazepine antagonism.
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PMID:Time-dependent anticonvulsant activity of melatonin in hamsters. 161 1

Preincubation of rat forebrain membranes for 30-60 min with micromolar concentrations of the pineal hormone, melatonin, significantly inhibited forskolin-stimulated adenylate cyclase (AC) activity. Melatonin had an EC25 (concentration which inhibited AC activity by 25%) of 600 microM and caused a maximal inhibitory effect of approximately 30% at a concentration of 1000 microM. A comparison of the effects of melatonin and its analogs, 6-chloromelatonin and 2-iodomelatonin, in the striatum revealed that these halogenated drugs were 2-3 times more potent than melatonin in inhibiting AC activity. The EC25 values were 611, 226 and 189 microM for melatonin, 6-chloromelatonin and 2-iodomelatonin respectively. The receptor antagonists phentolamine (alpha-adrenergic), propranolol (beta-adrenergic), and metergoline (serotonergic) did not block the effect of melatonin in forebrain membranes. The central-type benzodiazepine (BZ) antagonist, Ro 15-1788 (flumazenil), also failed to block the inhibitory effects of melatonin, and the benzodiazepines, diazepam and Ro 5-4864, on AC activity. Evidence that inhibition of adenylate cyclase activity may be involved in the prevention of seizures suggests that the reported anticonvulsant effect of large doses of melatonin may be due to this mechanism. The greater potency of the halogenated melatonin analogs in inhibiting AC suggests that further study of their potential usefulness as anticonvulsants would be worthwhile.
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PMID:Pharmacological inhibition of forskolin-stimulated adenylate cyclase activity in rat brain by melatonin, its analogs, and diazepam. 226 Sep 93

Pinealectomy of the Mongolian gerbil leads to seizure activity. The pineal gland is a major source of malatonin (5-methoxy-N-acetyltryptamine) which may possess a modulatory influence upon neural activity. Melatonin administered in the form of subcutaneous beeswax implants was given to gerbils four days prior to pinealectomy or sham pinealectomy. Beeswax pellets were implanted as the vehicle agent in respective groups. Melatonin-treated pinealectomized animals exhibited fewer seizures than did pinealectomized animals that did not receive melatonin. The results indicate that melatonin has an ameliorative effect upon pinealectomy-induced seizures, but the mechanism by which pinealectomy induced the seizures, and the etiology in which melatonin reduces the seizure activity is unknown.
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PMID:Antiepileptic effects of melatonin in the pinealectomized Mongolian gerbil. 735 40

In recent years an increasing amount of data has been published involving melatonin in the control of brain function. The pineal gland exerts a depressive influence on CNS excitability. This activity is linked to melatonin, since pharmacological doses of the hormone prevent seizures in several animal models. In addition, melatonin also has analgesic properties in these species. However, the sites and mechanism of melatonin action are not known. A role for the pineal gland and its hormone melatonin as a homeostatic system controlling brain excitability has been proposed, and GABA-containing neurons may be involved in some central action of melatonin. There is evidence supporting a role of melatonin in the regulation of the GABA-benzodiazepine receptor complex, and it appears that melatonin potentiates this inhibitory neurotransmitter system in brain. Melatonin does not bind to GABA or benzodiazepine binding sites themselves, because in vitro binding data showed that melatonin is a weak competitor of benzodiazepine binding in brain membranes at concentrations greater than 10(-5) M. The effect of melatonin on brain activity also involves the participation of corticotropic and opioid peptides, and the existence of an opioid-antiopioid homeostatic system is proposed, with the GABA-benzodiazepine receptor complex as an effector. Moreover, the interaction of melatonin with corticotropic peptides and mitochondrial benzodiazepine receptors may result in a participation of neurosteroids in the control of GABA activity and function. The most recently available data from biochemical and electrophysiological studies support the possibility that the anticonvulsant and depressive effects of melatonin on neuron activity may depend on its antioxidant and antiexcitotoxic roles, acting as a free radical scavenger and regulating brain glutamate receptors. The full characterization of the nuclear melatonin receptor explains the genomic effects of melatonin, opening a new perspective regarding actions and roles of melatonin as a cellular protector.
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PMID:Cell protective role of melatonin in the brain. 860 97

Melatonin, a hormone produced in the pineal gland and released into the general circulation on a diurnal basis, has been implicated in many behavioral processes, where it has been shown to have anxiolytic, sedative, and anticonvulsant effects. Male gerbils (Meriones unguiculatus) injected daily with melatonin (25 micrograms, s.c.) exhibited a reduced seizure response to pentylenetetrazol (PTZ, 60 mg/kg, s.c.). The present studies determined 1) whether melatonin's effect was related to the time of day that it was administered and 2) whether a single acute injection of melatonin at various doses could produce anticonvulsant activity. Gerbils provided with 13 weeks of daily melatonin injections (25 micrograms, s.c.) exhibited fewer convulsions after PTZ treatment irrespective of the time of day melatonin was injected. In addition, the melatonin-treated gerbils had lower mortality rates (1/12) than the untreated or vehicle-injected gerbils (5/12). On the other hand, single acute injections of melatonin (0.1-10 mg/kg, i.p.) produced no anticonvulsant activity. It appears that the anticonvulsant effects of melatonin occur only after the animals are chronically exposed to the indole. In addition, melatonin's anticonvulsant ability may utilize a different mechanism than those involved in its endocrine effects, since no diurnal difference in melatonin's anticonvulsant activity was observed.
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PMID:Acute and chronic effects of melatonin as an anticonvulsant in male gerbils. 881 91

Recent data indicate that melatonin inhibits brain glutamate receptors and nitric oxide production, thus suggesting that it may exert a neuroprotective and antiexcitotoxic effect. Melatonin has been seen to prevent seizures in several animal models and to decrease epileptic manifestations in humans. The lack of response to conventional anticonvulsants in an epileptic child led us to use melatonin in this case. A female child who began to have convulsive seizures at the age of 1.5 months and was diagnosed as having severe myoclonic epilepsy was unsuccessfully treated with different combinations of anticonvulsants, including valproic acid, phenobarbital, clonazepam, vigabatrin, lamotrigin, and clobazam. Melatonin was thus added to the treatment. Imaging studies (CT, SPECT, and MNR), EEG recordings, blood biochemical, and hematological analyses, including measures of the circadian rhythm of melatonin, were made. The child was initially treated with various anticonvulsants. Severe neurological and psychomotor deterioration combined with increased seizure activity showed a lack of response to the treatment. At the age of 29 mon the patient was in a pre-comatose stage at which time melatonin was added to treatment. After 1 month of melatonin plus phenobarbital therapy and for a year thereafter, the child's seizures were under control. On reducing the melatonin dose after this time, however, seizures resumed and the patient's condition was re-stabilized after restoring melatonin. Prior to our attempts to reduce melatonin, all analyses, including EEG recordings and SPECT, were normal. As far as the results of neurological examination are concerned, only mild hypotony without focalization remained. Changes in the therapeutic schedules during the second year of melatonin treatment, including the withdrawal of phenobarbital, did not result in the same degree of seizure control, although progressively the child became satisfactorily controlled. At the present moment the child continues to have mild hypotony and shows attention disorder and irritability. Melatonin has proven to be useful as adjunctive therapy in the clinical control of this case of severe infantile myoclonic epilepsy. The results suggest that melatonin may have a useful role in mechanisms of neuroprotection and also indicate its use in other cases of untreatable epilepsy. Further studies using more patients and placebo-treatment would be beneficial in understanding the potential use of melatonin as a co-therapy in some cases of seizures.
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PMID:Utility of high doses of melatonin as adjunctive anticonvulsant therapy in a child with severe myoclonic epilepsy: two years' experience. 939 48

The brain consumes large quantities of oxygen relative to its contribution to total body mass. This, together with its paucity of oxidative defense mechanisms, places this organ at risk for damage mediated by reactive oxygen species. The pineal secretory product melatonin possesses broad-spectrum free radical scavenging and antioxidant activities, and prevents kainic acid-induced neuronal lesions, glutathione depletion, and reactive oxygen species-mediated apoptotic nerve cell death. Melatonin's action is thought to involve electron donation to directly detoxify free radicals such as the highly toxic hydroxyl radical, which is a probable end-product of the reaction between NO. and peroxynitrite. Moreover, melatonin limits NO.-induced lipid peroxidation, inhibits cerebellar NO. synthase, scavenges peroxynitrite, and alters the activities of enzymes that improve the total antioxidative defense capacity of the organism. Melatonin function as a free radical scavenger and antioxidant is likely facilitated by the ease with which it crosses morphophysiological barriers, e.g., the blood-brain barrier, and enters cells and subcellular compartments. Pinealectomy, which eliminates the nighttime rise in circulating and tissue melatonin levels, worsens both reactive oxygen species-mediated tissue damage and brain damage after focal cerebral ischemia and excitotoxic seizures. That melatonin protects against hippocampal neurodegeneration linked to excitatory synaptic transmission is fully consistent with the last study. Conceivably, the decreased melatonin secretion that is documented to accompany the aging process may be exaggerated in populations with dementia.
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PMID:Excitotoxicity, oxidative stress, and the neuroprotective potential of melatonin. 1066 17

The production of melatonin by the pineal gland and its functions are considered, and then its possible uses in the treatment of children. Institutionalized children, and those with severe learning disorders, often have irregular sleep-wake patterns, and there is evidence that melatonin can result in improvement to the benefit of both the child and the carers. The affected children can become less irritable, calmer, happier, and content. Also they may socialize better and become more attentive, with an improvement in their cognitive abilities. Another group of children who are likely to suffer from disturbed sleep are those who are visually handicapped. Melatonin given in the evening can improve their sleep patterns, and often their performance. No important side-effects have been reported. It is generally accepted that if a child is liable to epileptic seizures sleep deprivation may well exacerbate them. There is some evidence from clinical trials that in that event melatonin can be helpful. There are many other problems in which it is claimed that treatment with melatonin is justifiable. These are mentioned, but further confirmatory studies are needed in most of them. There is no doubt that melatonin can effect the circadian system, and shift the sleep-wake cycle; and that there are situations in which this can be desirable.
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PMID:The therapeutics of melatonin: a paediatric perspective. 1083 5


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