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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 thiophosphoric acid alkaloid derivatives from Chelidonium majus L. (Ukrain, UKSR-222) on the central nervous system (CNS) of mice and rats was studied. Intraperitoneal (ip) administration of Ukrain in doses of 9.5 and 19 mg/kg for mice depressed spontaneous motor activity, decreased body temperature and potentiated the action of hexobarbital. Only in a dose of 19 mg/kg Ukrain produced analgesic action in the hot plate test. It had no protective effect against electroshock or pentetrazol-induced seizures. In rats, ip administration of Ukrain in dose of 14 and 28 mg/kg potentiated the action of amphetamine and apomorphine but had no effect on catalepsy induced by haloperidol. Ukrain used in dose 9.5, 14, 19 and 28 mg/kg antagonized the head twitches induced by 5-HTP and hyperthermia-induced by m-CPP. Biochemical studies indicated that Ukrain did not affect the NA and DA concentrations in the whole rats' brain and did not affect the 5-HT and 5-HIAA concentrations in the whole brain of rats. These findings demonstrate that the central action of Ukrain involves the stimulation of the dopaminergic system and the inhibition of the serotoninergic system.
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PMID:Basic central pharmacological properties of thiophosphoric acid alkaloid derivatives from Chelidonium majus L. 147 May 61

To clarify the role of the serotonergic system in limbic and thalamic epileptic activity, we examined the effects of 5-hydroxytryptophan (5-HTP, 20 and 40 mg/kg) on fully kindled seizures from the hippocampus and lateral geniculate nucleus. The intraperitoneal administration of 20 mg/kg 5-HTP exerted no anticonvulsant effect on hippocampal kindled seizures, and a higher dose (40 mg/kg) produced a significant reduction in the behavioral seizure stage. 5-HTP at 20 mg/kg displayed no suppressive effect on lateral geniculate seizures, and 5-HTP at 40 mg/kg significantly reduced both the seizure stage and afterdischarge duration. Our data suggest that serotonergic mechanisms play an inhibitory role in seizures kindled from these brain regions.
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PMID:Serotonergic inhibition of limbic and thalamic seizures in cats. 162 80

The aim of the present investigation was to look for the mechanisms causing disturbances in carbohydrate metabolism during the action of the epileptogenic agent methionine sulfoximine. The levels of glucose, glycogen, and indolamines were measured in seven different regions of rat brain. Methionine sulfoximine induced a decrease in serotonin level which was roughly dose-dependent. There were no obvious changes in tryptophan and 5-hydroxyindoleacetic levels in any area. Methionine sulfoximine induced the known increase in glucose and glycogen levels. The direct precursor of serotonin. 5-hydroxytryptophan, and benserazide (a decarboxylase inhibitor) were then injected into rats in association with methionine sulfoximine. In this case, methionine sulfoximine failed to induce seizures. Moreover, the serotonin level was unchanged and the carbohydrate content did not significantly increase. There was only a rise in 5-hydroxyindoleacetic acid level. This work shows a striking parallelism between serotonin decrease and glycogen increase.
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PMID:Possible involvement of indolamines in the glycogenic effect of the convulsant methionine sulfoximine in rat brain. 169 79

Cerebrospinal fluid from 8 patients with infantile spasms (mean age: 6.1 months) was collected before treatment. The concentration of cerebrospinal fluid tryptophan metabolites was analyzed using high-performance liquid chromatography and compared to metabolite concentrations in cerebrospinal fluid from 20 age-matched controls (mean age: 5.8 months). The levels of cerebrospinal fluid serotonin, 5-hydroxyindoleacetic acid, and kynurenine were significantly lower in infantile spasm patients compared to controls (P less than .05). In contrast, the levels of cerebrospinal fluid 3-hydroxykynurenine were significantly higher in infantile spasm patients than in controls (P less than .05). There were no significant differences in the levels of cerebrospinal fluid tryptophan and 5-hydroxytryptophan. Although the study population was small, these findings suggest that the presence of seizures in infantile spasms is associated with a decrease in serotonergic metabolites which, in turn, may indicate a decrease in serotonergic activity, altered clearance of these metabolites, or altered turnover in the direction of 3-hydroxykynurenine. The perturbance caused by increased 3-hydroxykynurenine and decreased kynurenine in the homeostatic balance between these 2 tryptophan metabolites could further contribute to the pathogenesis of infantile spasms.
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PMID:Studies on CSF tryptophan metabolism in infantile spasms. 172 1

Tryptophan (Trp), 5-HTP, 5-HT, 5-HIAA, HVA, and MHPG in CSF and total Trp(T-Trp), free Trp(F-Trp) and serotonin in serum were determined in 80 children with epilepsy and also in a control group. It was found that Trp, 5-HT, 5-HIAA in CSF and F-Trp in blood decreased in children with epilepsy. But the decrease of F-Trp was not the main cause of decreased 5-HT metabolism, because the no positive correlations among the four substances were found. Each of them returned to normal levels after the treatment with phenytoin or valproate. 5-HT concentration was negatively correlated with the frequency of the epilepsy episodes. 5-HIAA and HVA levels were relatively higher in the epileptics with brain damage as with compared with those who had no brain damage. The MHPG level was higher in the patients simple partial seizures. Complex partial epileptics and those patients receiving antiepileptic drugs had a lower serum T-Trp level. T-Trp was negatively correlated with the serum valproate concentration. Both T-Trp and F-Trp levels decreased in the patients treated with phenytoin.
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PMID:[Altered monoamine metabolism in children with epilepsy]. 186 59

We recently demonstrated that long-lasting photosensitivity is acquired as a result of kindling of the lateral geniculate nucleus (LGN), and that the LGN-kindled cat pretreated with D, L-allylglycine represents a useful model of epilepsy for drug studies. The present experiments studied anticonvulsant effects of a serotonin precursor, L-5-hydroxytryptophan (5-HTP), on photosensitivity in the LGN-kindled cat under D,L-allylglycine and on LGN-kindled seizures. 5-HTP suppressed both myoclonic responses and paroxysmal EEG discharges induced by photic stimulation in a dose-related manner. Photically-induced seizures were completely blocked 1.5-2 h after injection of 20 mg/kg 5-HTP. 5-HTP was also effective in reducing the afterdischarge duration and behavioral seizure stage in LGN-kindled seizures; following 40 mg/kg administration, no electroclinical seizures were elicited in the LGN-kindled cats. Serotonergic mechanisms may play an important role in epileptic photosensitivity; the 5-HTP suppressive effect on photosensitivity is at least partly due to reduced neuronal activity at the level of the LGN via serotonergic inhibition.
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PMID:Suppressive effects of L-5-hydroxytryptophan in a feline model of photosensitive epilepsy. 191 84

The effect of central serotonergic stimulation on hippocampal and neocortical electrical activity and behavior was studied in freely moving rats by administering: (a) tranylcypromine followed by tryptophan, (b) fluoxetine followed by 5-hydroxytryptophan, or (c) p-chloroamphetamine alone. In all rats, scopolamine-resistant hippocampal rhythmical slow activity (RSA), thought to be dependent on brain serotonin, maintained its normal relation to behavior, occurring in close correlation with Type 1 behaviors (postural changes, turning of the head, walking). This RSA was generally absent during stereotyped behavior (head weaving, forepaw treading, hindlimb splaying and tremor). Scopolamine-resistant neocortical low-voltage fast activity (LVFA), also though to be dependent on brain serotonin, was present during Type 1 behaviors and also during stereotyped behavior. Most rats that developed a full stereotyped behavior syndrome had behavioral and electrocortical seizures which were associated with a reduction in the amplitude of hippocampal activity. These seizures were suppressed by methysergide or benserazide. Metergoline (and methysergide to a lesser extent) suppressed the stereotypic behaviors of the serotonin syndrome, resulting in a striking increase in the locomotion caused by central serotonergic stimulation. Such locomotion was accompanied by RSA and LVFA. It was concluded that increased serotonergic activity in the CNS causes an increase in motor activity and a correlated increase in scopolamine-resistant hippocampal RSA and scopolamine-resistant neocortical LVFA and suggested that metergoline blocks serotonin receptors mediating stereotyped behaviors, thereby permitting the expression of serotonin-mediated locomotion.
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PMID:The effects of serotonergic stimulation on hippocampal and neocortical slow waves and behavior. 193 39

Myoclonus is a clinical term meaning a quick involuntary jerk, seen in normal subjects under certain circumstances, including sleep, and in certain disease states. It is important as a symptom that may impair function and as an indicator of neurological dysfunction. Not until patients with myoclonus and major functional disability were reported in the 1960s was attention given to understanding its basis and pharmacotherapy. Reports of myoclonus developing after anoxic brain injury, and its response to treatment with the serotonin precursor 5-hydroxytryptophan (5-HTP), drew special attention. Further experience showed that only a few patients with myoclonus benefit from 5-HTP therapy. Benzodiazepines (BDZs) are often helpful in the treatment of myoclonus. Their beneficial effects decline with chronic administration because of drug tolerance, and the theoretical basis for BDZ responses remains unclear. The relationships between myoclonus, clonus, and epilepsy are discussed, as is the possible contribution of slow signaling transmembrane receptors to synchronization of motoneuron firing, which is suggested as a hallmark of myoclonus. Myoclonus may originate in many CNS sites, but the brain-stem reticular formation is especially relevant to myoclonus. Brain-stem serotonin neurons have special influence on spinal motoneurons, on startle responses, and on myoclonus. Among 5-HT receptors, 5-HT1A receptors are related to some forms of myoclonus, although 5-HT2 receptors are also implicated. GABAA receptors are related to some forms of myoclonus. Blockade of GABAA receptors or GABA synthesis regularly evokes convulsive seizures, but administration of many GABA agonists and some GABA uptake blockers paradoxically may evoke myoclonus. Injection of GABA receptor blockers into some brain areas has anticonvulsant effects. Stimulation of GABAA receptors may therefore promote or antagonize myoclonus depending on which GABA receptors are involved, the state of the system, etc. The role of glycine receptors is well established in some animal models, but has yet to be clearly established for human myoclonus. Opiates may produce myoclonus when given intrathecally or in high dosage. The concept of excitant anesthetics and special function of certain GABA receptors is discussed.
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PMID:Myoclonus: analysis of monoamine, GABA, and other systems. 216 12

During the 20 years that have elapsed since clomipramine (chlorimipramine) was first marketed, it has become well established in the treatment of depressive illness, particularly treatment-resistant depression. However, in addition to its role as an antidepressant, attention is being focused on the use of clomipramine in 2 other areas of psychiatry: obsessive compulsive disorder and panic disorder. Short term clinical trials have shown that clomipramine is generally more effective than amitriptyline, imipramine, desipramine, nortriptyline or clorgiline in reducing obsessive compulsive symptoms. Clomipramine appears to produce some short term benefit with exposure therapy in patients with obsessive compulsive disorder. However, the efficacy of the drug after long term follow-up has not been fully investigated. The antiobsessional efficacy of clomipramine appears to be independent of its antidepressant activity. In patients with panic disorder with or without agoraphobia (DSM-IIIR), clomipramine reduces the frequency and severity of panic attacks within 7 to 21 days of beginning treatment and efficacy is maintained for at least 12 months. Clomipramine is more effective than imipramine, the generally accepted standard treatment for patients with panic disorder after 2 weeks' treatment, but after 6 or 10 weeks both drugs are similarly effective. Other double-blind studies have shown that clomipramine is more effective than placebo and at least as effective as fluvoxamine and oxitriptan (5-hydroxytryptophan) in reducing panic attacks and associated anxiety. Adverse effects associated with clomipramine treatment are mild to moderate in nature and are predominantly a result of the drug's anticholinergic activity. The incidence of seizures is dose related, occurring in 0.48% of all patients receiving clomipramine less than or equal to 250 mg/day and 2.1% of patients receiving greater than or equal to 300 mg/day. In conclusion, the available data indicate that clomipramine is a worthwhile addition to the limited treatments available for obsessive compulsive disorder and panic disorder, two psychiatric disorders which have previously been difficult to manage pharmacologically.
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PMID:Clomipramine. An overview of its pharmacological properties and a review of its therapeutic use in obsessive compulsive disorder and panic disorder. 217 9

The role of serotonin in the mediation of the anticonvulsant activity of JAW-669 was investigated against maximal electric shock (MES)-induced seizures in mice. A dose-dependent protection against seizures was provided by JAW-669 (4, 6 and 8 mg/kg, IP) and the calculated ED50 value was 6.01 mg/kg, IP. Pretreatment of mice with 5-hydroxytryptophan (50 mg/kg, IP) 2 hr before the administration of JAW-669 (6.01 mg/kg, IP) was found to cause a 40% increase in the ability of JAW-669 to provide protection against MES-induced seizures. Similar pretreatment with tryptophan (100 mg/kg, IP, 1 hr) caused a 30% decrease in the anticonvulsant activity of JAW-669. Prior administration of p-chlorophenylalanine (300 mg/kg, IP, 48 hr) and methysergide (10 mg/kg, IP; 0.5 hr) before administration of JAW-699 caused a 66% and 74% decrease, respectively, in the ability of JAW-669 to provide protection against MES-induced seizures. These results suggest a facilitatory role of serotonin in the anticonvulsant activity of JAW-669.
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PMID:Neuromodulatory role of serotonin in the anticonvulsant activity of 2-phenylbenzoate of 3-diethylamino-1-propanol.HCl (JAW-669). 253 Jun 1


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