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)

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.
 ...
PMID:Neuromodulatory role of serotonin in the anticonvulsant activity of 2-phenylbenzoate of 3-diethylamino-1-propanol.HCl (JAW-669). 253 Jun 1

The kynurenines, endogenous tryptophan metabolites with convulsant properties, have been postulated to play a role in the genesis of seizure disorders. We have previously reported that concentrations of 3-hydroxykynurenine (3-HK) higher than 0.2 mM are present in the brains of neonatal rats perinatally deprived of vitamin B-6. At a 1 mM concentration 3-HK significantly decreased the affinity of 3H-flunitrazepam for benzodiazepine receptor sites in rat brain membrane preparations. Furthermore, lower concentrations (Ki = 250 microM) of 3-HK antagonized the enhancing effect of GABA on 3H-flunitrazepam binding. These results suggest that 3-HK may have a modulatory effect on the GABA/benzodiazepine/barbiturate receptor complex.
 ...
PMID:The putative endogenous convulsant 3-hydroxykynurenine decreases benzodiazepine receptor binding affinity: implications to seizures associated with neonatal vitamin B-6 deficiency. 285 May 79

Despite intense investigation, the role of serotonergic neurons in audiogenic seizures in mice remains uncertain. In the work reported here, audiogenic seizure susceptibility and brain tryptophan and serotonin concentrations were measured in DBA/2J mice after administration of three doses of L-tryptophan or p-chlorophenylalanine. p-Chlorophenylalanine reduced brain serotonin and significantly prolonged the latency to appearance of all seizure phases. L-tryptophan was largely ineffective in protecting against seizures and in elevating brain serotonin content, despite the fact that it caused a marked increase in brain tryptophan content. Thus, it appears that DBA/2J mice have an impaired ability to synthesize serotonin from tryptophan.
 ...
PMID:Audiogenic seizures and brain serotonin after L-tryptophan and p-chlorophenylalanine. 293 72

Selective antagonists of quinolinic acid (2,3-pyridine dicarboxylic acid, QUIN)--an endogenous convulsant tryptophan metabolite, administered intracerebroventricular to mice, were identified during comparison with the following intracerebroventricular convulsants: l-kynurenine, aspartic, glutamic, N-methyl-DL-aspartic and kainic acids. It is suggested that the antagonism arises due to a common fragment of the structure which consists of two carboxylic groups at two nearest carbon atoms of the ring and of one nitrogen atom in the alpha-position. The selective action of the compounds found against QUIN supports the suggestion that QUIN produces seizures via N-methyl-D-aspartate binding sites.
 ...
PMID:[Selective anticonvulsive action of N-substituted imidazole-4,5-dicarboxylic acids against quinolinic acid]. 296 57

The onset of therapeutic effectiveness of carbamazepine is generally very rapid in the treatment of seizure and paroxysmal pain disorders, shows some lag in the treatment of mania, and exhibits the longest lag in depression. These time course variations may indicate that different mechanisms underlie the efficacy of carbamazepine in the differential neuropsychiatric syndromes. Biochemical and pharmacological data suggest that the anticonvulsant effects of carbamazepine are related to "peripheral-type" benzodiazepine and alpha 2-noradrenergic receptor systems and to its ability to stabilize sodium channels. GABAB (baclofen-like) actions appear to be involved in antinociceptive, but not anticonvulsant, effects. The relatively acute time course of antimanic efficacy may be related to the above-mentioned mechanisms or to other effects related to systems postulated to be altered in the manic syndrome. These effects might include carbamazepine's ability to increase acetylcholine in the striatum, decrease probenecid-induced levels of CSF homovanillic acid (HVA) in man and dopamine turnover in animals, decrease CSF norepinephrine in manic patients, inhibit adenylate cyclase activity (in response to norepinephrine, dopamine, adenosine, or ouabain), decrease GABA turnover, or act as a vasopressin agonist. Efficacy in depression may be related to actions in man that take time or chronic drug administration to develop, such as increases in plasma tryptophan, decreases in CSF somatostatin, decreases in thyroid indices, and increases in urinary free cortisol excretion and, in animals, increases in substance P sensitivity and increases in brain adenosine receptors. The ability of carbamazepine to block the development of lidocaine- and cocaine-induced seizures also requires chronic administration, suggesting that these seizure models may provide a unique perspective for understanding mechanisms of time-dependent effects.
 ...
PMID:Time course of clinical effects of carbamazepine: implications for mechanisms of action. 328 May 60

The disposition of kynurenic acid (KYNA), a tryptophan metabolite and broad spectrum antagonist at excitatory amino acid receptors, was studied following the unilateral intrahippocampal injection of 3H-KYNA in the rat. KYNA was rapidly cleared from the injected hippocampus. Similar decay curves were observed in several brain regions ipsi- and contralateral to the injection site as well as in serum and renal tissue. The radioactivity retained in tissue or excreted in urine for the first two hours after a 3H-KYNA injection was identified as unmetabolized KYNA. Moreover, direct measurement in hippocampal slices failed to provide evidence for the presence of specific cellular uptake mechanisms for KYNA. The present results do not support a neurotransmitter function for KYNA in the rat brain. However, they do not rule out a role of KYNA in the pathogenesis of neurodegenerative and seizure disorders.
 ...
PMID:On the disposition of intrahippocampally injected kynurenic acid in the rat. 341 69

From day 1 to day 3, the protein intake of this neonate was restricted to 1 g/kg/d. It included a) essential amino acids (i.e. histidine, lysine, threonine, tryptophan), b) arginine (1,000 mg/d), c) alphaketoisovaleric 500 mg/d, alpha-ketoisocaproic (500 mg/d), alphaketobetamethylvaleric (500 mg/d), alphaketogammamethylthiobutyric (200 mg/d), betaphenylpyruvic (400 mg/d) acids. 250 mg/kg/d of sodium benzoate were given. Caloric and water intakes were 120 cal/kg/d and 120 ml/kg/d respectively. Afterwards, this procedure was modified according to clinical and biological data including serum ammonia and amino acid levels. Alpha-ketonic acid absorption and metabolism were studied on day 29. Both were fast. The detection of alloisoleucine, which is not metabolized was the consequence of the use of alphaketobetamethylvaleric acid. Until the age of 21 months, clinical and metabolic status was satisfactory. At this time, repeated seizures without metabolic failure were accompanied by psychomotor damages.
 ...
PMID:[Treatment of citrullinemia. Apropos of a case followed from birth. Importance of alpha-ketonic acids]. 344 58

The convulsive response to pentylenetetrazol was investigated in rats receiving different dietary tryptophan inputs. In the first experiment the animals were fed either a corn or a corn-supplemented diet. In the second one they received either a control diet supplemented with tryptophan, a low-protein/high-carbohydrate diet, or a low-protein/high-carbohydrate tryptophan-supplemented diet. The control groups for both experiments were fed a diet containing 22% milk protein. The corn diet facilitated seizures; the low-protein/high-carbohydrate/tryptophan diet prevented seizures. These results suggest that the brain serotonin levels determined by dietary tryptophan, or tryptophan by itself, could play a role in the convulsive response.
 ...
PMID:Does dietary tryptophan play a role in the control of convulsive activity? 345 94

Vitamin B-6 deficient rats exhibit changes in behavior, sensory function, and other nervous system abnormalities such as convulsive seizures and motor disturbances. Sensorimotor reactivity was evaluated quantitatively by measuring auditory and tactile startle responses in 12 week old female Long-Evans rats fed a diet devoid of added vitamin B-6 (DEF) or a control diet, either ad lib (AL-CON) or pair-fed to deficient rats (PF-CON). Deficiency was confirmed with a tryptophan-load test administered to a separate group of rats fed simultaneously according to the same protocol. At week 18, body weight and feed efficiency were different among groups (p less than 0.001), and were lowest in DEF. Amplitude of response to both acoustic and tactile stimuli was depressed in DEF compared to both control groups, which generally did not differ in response. This effect was seen most dramatically in responses to the acoustic stimulus (p = 0.034), and especially to the first presentation (p = 0.017). Latency to maximum response was not affected by diet. Possible mechanisms for this nervous system abnormality, not previously reported in vitamin B-6 deficiency, are discussed.
 ...
PMID:Attenuation of acoustic and tactile startle responses of vitamin B-6 deficient rats. 362 44

Increased concentrations of the endogenous tryptophan metabolite 3-hydroxykynurenine (3-HK) were measured in the brains of vitamin B6 deficient neonatal rats. Mean concentrations of 3-HK in B6 deficient cerebellum, corpus striatum, frontal cortex, and pons/medulla ranged from 9.7 to 18.6 and 102 to 142 nmol/g of wet tissue at 14 and 18 days of age, respectively. 3-HK was not significantly increased in control neonatal or adult rat brain, vitamin B6 deficient rat brain at 7 days of age, or in brains from adult rats deprived of vitamin B6 for 58 days. The administration of daily intraperitoneal injections of vitamin B6 from the 14th to the 18th day of age decreased the concentration of 3-HK to control levels. 3-HK has been shown by other investigators to produce seizures when injected into the cerebral ventricles of adult rodents. Thus, our studies show the accumulation in brain of a putative endogenous convulsant as the result of a nutritional deficiency.
 ...
PMID:Increased concentrations of 3-hydroxykynurenine in vitamin B6 deficient neonatal rat brain. 368 2


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