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)

The putative cognition enhancer linopirdine (3,3-bis(4-pyrindinylmethyl)-1-phenylindolin-2-one, CAS 105431-72-9) is supposed to act by enhancing the release of neurotransmitters, especially acetylcholine. The present study assessed the effects of a single administration of this compound on the central nervous system in eight different rat and mouse models (CNS general pharmacology). In each test performed, linopirdine was administered subcutaneously in doses of 3, 10, and 30 mg/kg. The compound did not affect traction ability and nociceptive responsiveness nor did it induce catalepsy. Linopirdine impaired motor coordination in the balance rod test. The compound showed a distinct proconvulsive action in the pentylenetetrazole threshold dose test and induced in the highest dose tested (30 mg/kg) lethal seizures in some mice. It increased the duration of hexobarbital-induced anaesthesia in mice. Rats treated with linopirdine showed ptosis, salivation, slight sedation, paw beating and slight hypothermia. These results support the hypothesis that linopirdine acts by elevating the release of different neurotransmitters such as acetylcholine and dopamine. The compound has a low potential to produce side effects at pharmacodynamic active doses.
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PMID:General pharmacology of the putative cognition enhancer linopirdine. 777 41

The general pharmacological properties of a novel cognition-enhancing agent, nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide, DM-9384, CAS 77191-36-7) were investigated, and the following results were obtained. 1. Central nervous system: Nefiracetam showed depressant activities (such as ataxia) on general behavior (mice), and inhibited spontaneous locomotor activity, rota-rod and traction performances (mice) and polysynaptic potential of the spinal reflex (rats), and potentiated pentobarbital anesthesia (mice). The drug inhibited electroshock-induced seizure at relatively low doses, but did not affect chemoshock-induced seizure (mice). Nefiracetam failed to show analgesic activity in the tail pinch test, but inhibited the acetic acid-induced writhing syndrome (mice). An inhibitory pattern in the electroencephalogram was observed (cats). Nefiracetam had little or no effect on body temperature (rats). 2. Respiratory and cardiovascular systems: Nefiracetam induced transient decreases in blood pressure, left ventricular pressure and LV dp/dt max at higher doses (dogs). 3. Autonomic nervous system: Nefiracetam had no influence on pupil size (rabbits). The drug induced no significant effect on the pressor response to norepinephrine or depressor response to acetylcholine, but inhibited the contractile response of the nictitating membrane to preganglionic cervical sympathetic nerve stimulation at the highest dose (dogs). 4. Gastrointestinal system: Nefiracetam inhibited gastrointestinal propulsion (mice), gastric emptying rate and gastric secretion (rats) at higher doses. Nefiracetam produced no apparent damage in the gastric mucosa, and had no effect on bile secretion (rats). 5. Isolated smooth muscle: Nefiracetam had no effect on the resting tonus of isolated ileum, whereas it inhibited the contractile response to acetylcholine, histamine, serotonin, nicotine and BaCl2 at higher concentrations (guinea pigs). Nefiracetam had no effect on the resting tonus or the serotonin-induced contraction of stomach fundus (rats). The drug had no effect on the resting tonus or the norepinephrine-induced contraction of vas deferens, but tended to inhibit the contraction induced by nerve stimulation (guinea pigs). Nefiracetam had little or no effect on the resting tonus or oxytocin-induced contraction of virgin uterus, or on spontaneous contraction of pregnant uterus (rats). Nefiracetam did not affect the resting tonus of trachea, whereas it inhibited isoproterenol-induced relaxation at the highest concentration (guinea pigs). Nefiracetam had no chronotropic effect in isolated atria, but showed a slight negative inotropic effect at the highest concentration (guinea pigs). 6. Miscellaneous: Nefiracetam slightly decreased urinary volume, whereas it did not affect urinary electrolyte excretion (rats).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:General pharmacological profile of the new cognition-enhancing agent nefiracetam. 801 90

The pharmacological effects of the novel fluoroquinolone 7-(1R,4R-2,5-diazebicyclo[2.2.1]heptan-2-yl)-1-(1,1-dimethyl )ethyl-6-fluoro - 4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (BMY-40062, CAS 116143-32-9) on central nervous system were investigated in mice and rats, in comparison in some cases with those of reference quinolones. BMY-40062 showed no effect on general behavior, spontaneous activity, body temperature and neuromuscular coordination in rats at the doses of 1000 and 250 mg/kg. None of the quinolones tested including BMY-40062 modified the seizures induced by bicuculline, a specific GABA A antagonist. BMY-40062 and ciprofloxacin did not consistently influence the pentetrazol-induced convulsions. On the contrary, pefloxacin exhibited a marked convulsivant activity. In the fenbufen (non-steroidal anti-inflammatory drug)-induced seizure model, BMY-40062 showed no effect. Enoxacin, norfloxacin followed by ciprofloxacin elicited a convulsivant effect in presence of fenbufen. Under these experimental conditions, BMY-40062 had no effect on the central nervous system compared to the other tested quinolones in rodents.
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PMID:Pharmacological properties of a new fluoroquinolone on the central nervous system in rodents. 844 50

Various combinations of carbamazepine (CAS 298-46-4), felbamate (CAS 25451-15-4), and phenytoin (CAS 57-41-0) were evaluated in mice (i.p.) for anticonvulsant activity (maximal electroshock seizure test) and minimal neurotoxicity (rotarod test). The results obtained from these studies were analyzed using response surface methodologies (RSM). The outcomes of these analyses in regard to anticonvulsant activity suggest that, under these experimental study conditions, at 0.5 h post treatment there is a significant carbamazepine/phenytoin synergism even though none of the drugs has a significant dose-response by that time when given alone, and that at 1.0 h post treatment, the combination dose-response is additive. Thus, there appears to be an important dose/time relationship. In regard to the neurotoxic response, the results suggest a significant carbamazepine/phenytoin synergism at 0.25 h post treatment and an additive neurotoxic effect due to the combination of felbamate/carbamazepine/phenytoin at 0.5, 1.0 and 2.0 h post exposure.
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PMID:Analysis of anticonvulsant and neurotoxic responses to combination therapy with carbamazepine, felbamate and phenytoin by response-surface modeling. 857 14

Carbamazepine (CAS 298-46-4), an iminostilbene derivative and a structural congener of the tricyclic antidepressant drugs, has been used in the treatment of epileptic seizures since 1963. The bioavailability/bioequivalence of a carbamazepine sustained release formulation (Timonil retard) was compared with a reference formulation in an open 2-period crossover study in 21 healthy male volunteers (including 1 drop-out) after multiple dose administration. During a run-in phase of 6 days the daily dose was gradually increased from 100 to 400 mg. On days 9 to 15, either the test or the reference formulation was administered twice daily, followed by a switch of preparation for a further 7 days of treatment (days 16 to 22). On the pharmacokinetic profiling days 15 and 22 blood samples were drawn over a 24-h period. In addition, blood samples were withdrawn before morning administrations for determination of carbamazepine and carbamazepine-10,11-epoxide trough values. Plasma concentrations of carbamazepine and its metabolite carbamazepine-10,11-epoxide were determined using a specific and sensitive HPLC method with UV detection. The results showed that autoinduction of carbamazepine metabolism under the chosen dosage regimen was complete within 14 days after start of treatment and that the criteria for bioequivalence were met. The 90% confidence intervals of all ratios were included by a range of 80-125% (AUC0-12: 103-120; AUC12-24: 105-119; Cmax0-12: 104-118; Cmax12-24: 104-118). During the study, 12 subjects experienced a total of 24 adverse events with mild to moderate intensity. Due to a significant increase of liver enzyme activity in serum during the course of the study, one subject was excluded from further study participation. There were no serious adverse events. It was concluded that the test formulation is bioequivalent to the reference formulation with respect to rate and extent of absorption.
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PMID:Bioavailability study of two carbamazepine containing sustained release formulations after multiple oral dose administration. 989 26

2-Amino-5-(heteroarylmethylene)-1,3,4-oxadiazoles/thiadiazoles 7-10 were synthesized by cyclisation of 1-(heteroarylacetyl)semicarbazides/thiosemicarbazides 3-6. 5-(2'-Heteroarylmethylene-5'-aminomethylene-1',3,'4'- oxadiazol-2'-yl/thiadiazol-2'-yl)-2-oxo/thiobarbituric acids 11-18 were synthesized by condensation of compounds 7-10 at the 5th position of 2-oxo/thiobarbituric acids. The newly synthesized compounds showed anticonvulsant activity ranging from 50-90% (seizures protection). Compound 18 (5-(2'-phenothiazinylmethylene-5'-aminomethylene-1',3',4'-thiadiazol-2'- yl)-2-thiobarbituric acid) showed maximum activity being more potent than the reference drug phenytoin sodium (CAS 630-93-3).
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PMID:Synthesis of newer indolyl/phenothiazinyl substituted 2-oxo/thiobarbituric acid derivatives as potent anticonvulsant agents. 1285 56

The anticonvulsant activity of a homologous series of DL-dichlorophenyl alcohol amides is described. The compounds DL-2-hydroxy-2-(3',4'-dichlorophenyl) butyramide (4, CAS 620950-11-0), DL-3-hydroxy-3-(3',4'-dichlorophenyl) pentanamide (5, CAS 620950-15-4) and DL-4-hydroxy-4-(3',4'-dichlorophenyl) hexanamide (6, CAS 620950-17-6 ) were prepared and tested. Compounds 4, 5 and 6 exhibited a significant activity in seizures induced by pentetrazol. Incorporation of chlorine in the phenyl ring increased their potency. Compound 4 exhibited a slightly lower activity than the reference drug phenobarbital (CAS 50-06-6).
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PMID:Synthesis and pharmacological evaluation of some DL-dichlorophenyl alcohol amides anticonvulsants. 1564 66

Eighteen 1-phenyl-, 1-thiocarbamoyl- and 1-N-substitutedthiocarbamoyl-3-phenyl-5-heteroaryl-2-pyrazoline derivatives were synthesized and tested for their antidepressant and anticonvulsant activities. Their chemical structures were proved by spectral and microanalysis. The antidepressant activities of the compounds were investigated by the "forced swimming test". Results showed that compounds II-a, b, c, III-1b, 1c, 4a showed activities equivalent to or higher than pargyline hydrochloride (CAS 306-07-0) and tranylcypromine sulfate (CAS 13492-01-8) that were used as reference antidepressant drugs. Anticonvulsant activities of the compounds were determined by maximal electroshock seizure (MES), subcutaneous metrazol (ScMet.) and rotarod toxicity tests in mice according to the phase I tests of the Antiepileptic Drug Development programme. Compounds I-a, II-a, b, c, III-1b, 2a, 2c were found protective against MES and III-1b, 1c, 2a, 2c were found protective against ScMet.
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PMID:Synthesis of and pharmacological studies on the antidepressant and anticonvulsant activities of some 1,3,5-trisubstituted pyrazolines. 1614 9

The anticonvulsant activity of some DL-hydroxybenzenamides is described. The following compounds from this series were prepared and tested: DL-2-hydroxy-2-(3'-bromophenyl)butyramide (4, CAS 620950-12-1), DL-2-hydroxy-2-(4'-bromophenyl)butyramide (5, CAS 620950-13-2), DL-2-hydroxy-2-(3'-nitrophenyl)butyramide (6, CAS 620950-14-3), DL-2-hydroxy-2-phenyl hexanamide (7, CAS 63002-05-1), DL-2-hydroxy-2-(3',4'-dichlorophenyl)hexanamide (8, CAS 863976-06-1), DL-3-hydroxy-3-(4'-bromophenyl)pentanamide (9, CAS 620950-16-5), DL-3-hydroxy-3-phenyl-heptanamide (10, CAS 863976-08-3) and DL-4-hydroxy-4-(4'-bromophenyl)hexanamide (11,CAS 620950-18-7). Compounds 4, 5, 9 and 11 exhibited significant activity in seizures induced by pentylenetetrazol. Incorporation of bromine in the phenyl ring increased their potency. Compounds 4, 5, 9 and 11 exhibited a similar anticonvulsant activity as the reference drug phenobarbital (CAS 50-06-6).
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PMID:Synthesis of DL-hydroxybenzenamides as anticonvulsants. 1848 5

DL-2-Hydroxy-2-phenyl butyramide (1, CAS 52839-87-9), DL-3-hydroxy-3-phenyl pentanamide (2, CAS 131802-69-2) and DL-4-hydroxy-4-phenyl hexanamide (3, CAS 67880-30-2) are anticonvulsants. Searching for more active compounds, some DL-fluorobenzenamides were prepared and tested: DL-2-hydroxy-2-(3'-trifluoromethylphenyl)butyramide (4), DL-2-Hydroxy-2-4'-trifluoromethylphenyl) butyramide (5, CAS 620950-10-9), DL-2-hydroxy-2-[3',5'-bis(trifluoromethyl)phenyl]butyramide (6, CAS 620950-09-6), DL-3-hydroxy-3-(3'-trifluoromethylphenyl) pentanamide (7), DL-3-hydroxy-3-(4'-trifluoromethylphenyl)pentanamide (8), and DL-3-hydroxy-3-[3',5'-bis(trifluoromethyl)phenyl]pentanamide (9, CAS 863976-07-2). Compounds 4-9 exhibited anticonvulsant activity in seizures induced by pentylenetetrazol in mice. Incorporation of trifluoromethyl groups in the phenyl ring of 1, 2 and 3 increased their potency. Compounds 4, 6 and 9 exhibited a similar anticonvulsant activity as the reference drug phenobarbital (CAS 50-06-6).
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PMID:Synthesis of DL-fluorobenzenamides as anticonvulsants. 1854 Apr 76


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