Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:4432-31-9 (MES)
 1,294 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Six barbiturates with diverse time-action characteristics--thiopental, pentobarbital, butabarbital, phenobarbital, diphenylbarbiturate, and barbital--were evaluated for "anticonvulsant" and "neurotoxic" effects. For the former, the MES test, clonic seizures induced by pentylenetetrazol, 90 mg/kg, s.c., and maximal seizures produced by pentylenetetrazol, 200 mg/kg, s.c., were employed. For the latter, we used a rotorod technique. Time to peak activity in the MES test was employed as the time for other tests. Pentobarbital required at least neurotoxic doses to produce substantial "anticonvulsant" activity, its protective index ranging from 0.79 to 0.98 in the three tests. Among the drugs tested, phenobarbital and diphenylbarbiturate exhibited the most favorable protective indices, ranging from 2.71 to 3.41 for phenobarbital and from 3.85 to 5.0 for diphenylbarbiturate. Barbital, another drug with a prolonged duration of action, exhibited a range from 0.84 to 2.81. Although a prolonged duration of action is an important characteristic for antiepileptic activity, this property does not confer per se a favorable protective index.
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PMID:Differential selectivity of several barbiturates on experimental seizures and neurotoxicity in the mouse. 3 70

Diphenylpropylamine has antiextensor activity in the MES test and worsens clonic seizures produced by pentylenetetrazol. The drug also prevents tonic hindlimb extension produced by large doses of pentylenetetrazol. Diphenylpropylamine appears, therefore, to be a phenytoin-like compound. However, unlike most antiextensor agents, diphenylpropylamine has neuroexcitatory effects and antagonizes barbital-induced loss of the righting reflex.
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PMID:Antiextensor effects of 3,3-diphenyl-n-propylamine in the mouse. 63 51

delta9-Tetrahydrocannabinol (THC) was compared with diphenylhydantoin (DPH), phenobarbital (PB) and chlordiazepoxide (CDP) using two electroshock procedures to determine anticonvulsant activity in mice, i.e., electroshock seizure threshold (EST) and the reduced EST caused by hyponatremia (injection of isotonic glucose). Using doses of each drug which were ineffective against MES, only CDP (10.0 mg/kg) was able to raise the EST by 20%. The lowered EST due to hyponatremia was reveresed by al four drugs. In these tests latency to convulsions and lethality associated with electroshock were more sensitive to THC.
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PMID:Comparative activity of delta9-tetrahydrocannabinol, diphenylhydantoin, phenobarbital and chlordiazepoxide on electroshcok seizure threshold in mice. 92 4

Ralitoline, a thiazolidinone derivative chemically distinct from known antiepileptic drugs, possesses remarkable anticonvulsant properties as demonstrated in various animal models of epilepsy. The efficacy of this compound seems to be comparable or even better than that of conventional antiepileptics. In the present study, the activity of ralitoline was investigated in four seizure models in rodents in order to characterize the anticonvulsant profile of action further. In the maximal electroshock seizure test (mice), this compound showed marked anticonvulsant effects (ED50 2.8 mg/kg i.p.). The efficacy of clinically established anti-epileptics was significantly increased when ralitoline was given as co-medication. In the strychnine seizure test (mice), ralitoline (5 and 10 mg/kg) prolonged the latency of tonic seizures as well as the survival time. On the other hand, in the subcutaneous pentylenetetrazol seizure threshold test (mice), this drug revealed limited protective actions at higher doses and increased the effectiveness of ethosuximide. In unrestrained rats with chronically implanted electrodes, ralitoline (5 mg/kg) significantly reduced the duration of electrically-evoked hippocampal discharges and raised the focal stimulation threshold (10 mg/kg). In the rotorod ataxia test (mice), a TD50 value of 14.5 mg/kg i.p. was determined for ralitoline (protective index TD50/MES-ED50 5.2). With regard to the possible mode of action, whole-cell voltage-clamp experiments on cultured neonatal rat cardiomyocytes showed that ralitoline may act specifically on voltage-sensitive sodium channels. The compound inhibited the fast sodium inward current in a frequency- and voltage-dependent manner. In conclusion, the findings confirm the potent anticonvulsant effects of ralitoline, especially against generalized tonic-clonic and complex partial seizures. Moreover, in combination with antiepileptics, an additive synergism can be found at lower concentrations. Regarding the mode of action, this drug was capable of depressing the fast sodium inward current in cultured heart ventricular cells, suggesting that the local anesthetic properties may be important for the anticonvulsant activity of ralitoline.
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PMID:Anticonvulsant and sodium channel blocking effects of ralitoline in different screening models. 133 17

The effects of NC-1100 on the central nervous system were analyzed behaviorally and electroencephalographically in mice, rabbits and mongolian gerbils, using ifenprodil as a control material. NC-1100 showed potentiating effects on spontaneous locomotor activities and excitatory motor activities induced by methamphetamine, but did not affect the rotarod test, traction test, sleeping time induced by pentobarbital, analgesic test, anticonvulsant test (MES and pentetrazol test), body temperature and group toxicity induced by methamphetamine. Following i.v. injection of NC-1100 to rabbits with chronically implanted electrodes, electroencephalographic properties in spontaneous EEGs such as fast waves with low voltages in the neocortex became distinguished slightly. Seizure discharges produced by stimulation of the dorsal hippocampus were slightly inhibited, but arousal responses produced by stimulation of the midbrain reticular formation or the posterior hypothalamic area were not inhibited. Furthermore, the effects of NC-1100 on functional recovery after transient cerebral ischemia in gerbils were not distinct. Based on these results, NC-1100 was considered to be an agent that improves cerebral metabolism and selectively increases cerebrovascular blood flow with few central nervous actions.
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PMID:[Effects of 1-(3,4-dimethoxyphenyl)-2-(4-diphenylmethylpiperazinyl)ethanol dihydrochloride (NC-1100) on the central nervous system]. 181 67

The effect of intrathecal administration of antiepileptic drugs on electroshock-induced convulsions (maximal electroshock seizure, MES test) was investigated in an experimental study in rats. Drugs tested were phenobarbital sodium (50-800 micrograms), sodium valproate (50-6,400 micrograms) and midazolam (50-250 micrograms), delivered into the cerebrospinal fluid via a catheter placed in the upper cervical intrathecal space. Control animals were tested with saline. The animals were tested in the MES test 30 min after drug administration. Phenobarbital sodium showed a dose-related protective effect on the tonic phase of the convulsion, with a 50% effect at a dose of 200 micrograms. Sodium valproate showed a less protective effect, even when reaching doses that produced neurological symptoms. Midazolam protected at a high dose but produced a severe decrease in motor activity. The results indicate the feasibility to treat experimental convulsions by means of intrathecal injection of antiepileptic drugs.
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PMID:Intrathecal antiepileptic drugs in experimental epilepsy. 181 35

Ralitoline (RLT) is a new thiazolidinone derivative with potent anticonvulsant activity in different seizure models. During Phase I studies, RLT was well tolerated in human volunteers and showed linear pharmacokinetics in the dose range tested (up to 150 mg). Since RLT will soon be entering clinical Phase II studies, we were interested in obtaining predictive data for effective plasma concentrations in patients. For this purpose, the anticonvulsant potency of RLT was determined in four seizure models in mice, and plasma levels were measured at time of peak drug effect. The four models were the threshold for maximal (tonic extension) electroshock seizures (MES), the threshold for clonic seizures determined by i.v. infusion of pentylenetetrazol (PTZ), the traditional MES test with supramaximal (50 mA) stimulation, and generalized clonic seizures induced by s.c. administration of PTZ. Furthermore, median minimal "neurotoxic" doses (TD50s) were determined by the rotorod and chimney test for calculation of protective indices. All data obtained for RLT were compared with data obtained with standard antiepileptic drugs: phenobarbital, phenytoin, valproate, and diazepam. The onset of anticonvulsant action after i.p. injection of RLT was very rapid, and the peak drug effect was already obtained after 2 min. In the MES models, RLT was the most potent compound. "Active" plasma levels ranged from approximately 300 ng/ml in the MES threshold test to approximately 1,300 ng/ml in the MES test. RLT was also capable of increasing the PTZ threshold, whereas, possibly because of its short duration of action in mice, it was not very active in the s.c. PTZ seizure test.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ralitoline: a reevaluation of anticonvulsant profile and determination of "active" plasma concentrations in comparison with prototype antiepileptic drugs in mice. 186 13

Effect of some histamine (HA) agonists and antagonists were assessed on electroshock (MES) convulsions in mice and rats. In mice, pretreatment with the HA precursor, l-histidine (100, 500 and 1000 mg/kg) precipitated seizures after a subthreshold (30 mA) stimulus. Both incidence (%) and tonic hind limb extensor phase (THE) were more than that in vehicle treated controls. The H1 blockers, pheniramine (25 mg/kg) and promethazine (25 mg/kg) both protected against (60 mA) MES and both incidence of convulsions and THE were reduced. A similar protective effect was not seen with either the H2 blocker, cimetidine (up to 200 mg/kg), or atropine (1 mg/kg). In rats, both the classical antihistamines blocked MES seizures, whereas, the H2-blocker, cimetidine, and atropine were, ineffective. Further, both H1 blockers were ineffective in antagonizing seizures induced by pentylenetetrazole, INH, caffeine or strychnine. These results are discussed in light of a possible HA-ergic regulation of experimental convulsions.
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PMID:Histaminergic mechanisms in experimental convulsions. 187 53

The pharmacological profile of PD117302 was studied in three rat models of experimental seizures. It was determined that PD117302 is a potent and efficacious anticonvulsant against NMDA (ED50 = 0.27 mg/kg, i.v.) and MES (ED50 = 16.3 mg/kg, s.c.), but not flurothyl, convulsions. Its anticonvulsant profile was dose- and time-dependent, stereospecific and sensitive to naloxone and the selective kappa opioid antagonist nor-binaltorphimine. Given these findings, we suggest that PD117302 acts via the kappa receptor to modulate seizure protection. Furthermore, in view of its marked ability to block NMDA excitotoxicity (including lethality) it seems possible that this drug, or related compounds, may have potential therapeutic utility as a neuroprotective agent.
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PMID:PD117302, a selective non-peptide opioid kappa agonist, protects against NMDA and maximal electroshock convulsions in rats. 216 36

A series of 4-(alkylimino)-5-hydroxy-7-alkyl-2,3-dihydro-4H-1-benzopyrans and -thiopyrans were synthesized and evaluated for anticonvulsant activity. Preliminary screening of these compounds revealed that 2,2-dimethyl-4-[(2-hydroxyalkyl)imino]-5-hydroxy-7-pentyl-2,3- dihydro-4H-1-benzopyrans 19 and 29, the 7-butyl analogue 34, and the corresponding 7-pentyl-4H-1-benzothiopyrans 38 and 39 had the most promising anticonvulsant activity. Synthesis of both enantiomers of 29 and 39 indicated that the R isomers 30 and 40 were the most active and showed very good protection against MES, pentylenetetrazole, and mercaptopropionic acid induced seizures after oral administration in mice. In the Irwin test these compounds showed a generalized depressant activity but at dosages higher than those showing anticonvulsant activity, whereas acute toxicity after oral administration was low (LD50 higher than 400 mg/kg).
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PMID:Synthesis and anticonvulsant and sedative-hypnotic activity of 4-(alkylimino)-2,3-dihydro-4H-1-benzopyrans and -benzothiopyrans. 221 38


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