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12. Effects of clonazepam on picrotoxin-induced convulsions
- Creator:
- Kubová, M., Bohuslav, T., and Mareš, P.
- Type:
- article, model:article, and TEXT
- Subject:
- epileptic seizures, GABAergic system, clonazepam, and picrotoxin convusions
- Language:
- English
- Description:
- The convulsant effects of four doses of picrotoxin (PX) - 2, 3, 4, and 6 mg/kg s.c. - were evaluated in the first part of the study. The 4- mg/kg dose, which elicited minimal seizures in all animals, generalized tonic-clonic (major) seizures in 75 % of rats and fatal outcome in 69 % of rats, was chosen for the second part, i.e. for testing the anticonvulsant action of clonazepam (Rivotril1* Roche, 0.1 or 1 mg/kg i.p.). Clonazepam exhibited a dose-dependent action against PX-induccd seizures, being more efficient against major than against minimal seizures.
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
13. Effects of MK-801 (dizocilpine) and ketamine on strychnine-induced convulsions in rats: comparison with benzodiazepines and standard anticonvulsants
- Creator:
- Kubová, H. and Mareš, P.
- Type:
- article, model:article, and TEXT
- Subject:
- motor seizures, strychnine, rats, NMDA antagonists, and antiepileptic drugs
- Language:
- English
- Description:
- The effects of two non-competitive NMDA antagonists - MK-801 and ketamine - were studied in a model of generalized seizures elicited by s.c. injection of strychnine (2 or 3 mg/kg) in adult rats. The animals were observed in isolation for 30 min after strychnine administration. Pretreatment with MK-801 (0.5 or 2 mg/kg i.p.) suppressed the tonic, but not the clonic phase of generalized seizures following both doses of strychnine. A similar action of ketamine (20 or 40 mg/kg i.p.) was indicated but it did not attain statistical significance. Strychnine-induced lethality was not changed significantly. A comparison with antiepileptic drugs demonstrated that only phénobarbital (10-80 mg/kg i.p.) was clearly effective against strychnine-induced seizures; carbamazepine (25 or 50 mg/kg i.p.) and partly phenytoin (30 or 60 mg/kg i.p.) were able to suppress the incidence of the tonic phase. Primidone (40 or 80 mg/kg i.p.) as well as the benzodiazepines bretazenil (0.1 or 1 mg/kg i.p.) and midazolam (two lower doses of 0.5 and 1 mg/kg i.p.) were without significant effect. The 2 mg/kg dose of midazolam was partly effective. Only phénobarbital, carbamazepine and the highest dose of midazolam prevented strychnine-induced lethality.
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
14. Excitatory Aminoacids and Epileptic Seizures in Immature Brain
- Creator:
- Mareš, P., Folbergrová, J., and Kubová, H.
- Type:
- article, model:article, and TEXT
- Subject:
- Pharmacology, NMDA receptors, nonNMDA receptors, Glutamate metabotropic receptors, Convulsions, Ontogeny, and Rat
- Language:
- English
- Description:
- Data on convulsant and anticonvulsant action of drugs influencing ex citatory amino acid receptors in developing rats are reviewed. Agonists of NMDA type of receptors NMDA and homocysteic acid, elicited an age-related seizure pattern – flexion, emprosthotonic seizures – in the first three postnatal weeks of rats. Generalized clonic-tonic seizures appeared only after a longer latency. Kainic acid administration resulted in epileptic automatisms and later in minimal, clonic seizures followed by generalized tonic-clonic seizures. A decrease of sensitivity to convulsant action with age is a general rule for all agonists tested. Different anticonvulsant action of NMDA and nonNMDA antagonists was demonstrated in a model of generalized tonic-clonic seizures induced by pentetrazol, whereas their action against epileptic afterdischarges elicited by electrical stimulation of cerebral cortex was similar. Again, higher efficacy in younger animals was a rule. As far as metabotropic glutamate receptors are concerned, agonists of groups II and III were shown to protect against convulsant action of homocysteic acid in immature rats and an antagonist of group I receptors MPEP suppressed the tonic phase of generalized tonic-clonic seizures induced by pentetrazol more efficiently in younger than in more mature rat pups. Unfortunately, a higher sensitivity to the action of antagonists of ionotropic glutamate receptors was demonstrated also for unwanted side effects (motor functions were compromized). In contrast, glutamate metabotropic receptor antagonist MPEP did not exhibit any serious side effects in rat pups.
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
15. Foreword
- Creator:
- Fenton, A. A. and Mareš, P.
- Type:
- article, model:article, and TEXT
- Language:
- English
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
16. Hippocampal afterdischarges in rats. I. Effects of antiepileptics
- Creator:
- Velíšek, L. and Mareš, P.
- Type:
- article, model:article, and TEXT
- Subject:
- Rat, Hippocampus, Epileptic afterdischarge, Antiepileptics, and wet dog shakes
- Language:
- English
- Description:
- Hippocampal afterdischarges (ADs) are considered to be a model of complex partial seizures. To study the pharmacology of these ADs, stimulation electrodes were implanted into the dorsal hippocampus of 33 male Wistar rats. Stimulation (15-s series of monophasic rectangular pulses with a duration of 1 ms and frequency of 8 Hz) was applied four times with interstimulation intervals of 15 min. Drugs (carbamazepine 50 and 100 mg/kg; clonazepam 0.2 and 0.5 mg/kg; ethosuximide 125 and 250 mg/kg; phenobarbital 40 and 80 mg/kg) as well as solvent and isotonic saline were injected intraperitoneally 2 min after the cessation of the first AD. Duration of AD, of the latent period between AD and recurrent AD and duration of recurrent AD and the number of wet dog shakes were measured. ADs were markedly shortened by both doses of clonazepam and phenobarbital and by the higher dose of carbamazepine. The action of ethosuximide was negligible. Wet dog shakes were influenced in the same way as AD duration. Recurrent ADs were more sensitive to antiepileptics than ADs and wet dog shakes.
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
17. Influence of carbamazepine and phenytoin on spontaneous activity of cerebellar neurons
- Creator:
- Buřitová, J., Hrabětová, S., Hrabě, J., Mareš, P., and Pavlík, V.
- Type:
- article, model:article, and TEXT
- Subject:
- rat, cerebellar neurones, carbamazepine, and phenytoin
- Language:
- English
- Description:
- Action of carbamazepine (50 mg/kg i.p.) and phenytoin (60 mg/kg i.p.) on the activity of cerebellar neurones was studied in rats under urethane anaesthesia. Carbamazepine markedly decreased the firing frequency of all ten neurones recorded continually before and after drug administration. The same conclusion was reached when a group of 53 cells recorded before drug administration was compared with 48 neurones recorded after carbamazepine administration only. The effects of phenytoin were ambiguous - a decrease as well as an increase in frequency was recorded. The solvent used did not change cerebellar unit activity. Cerebellum cannot be considered as a possible target structure for phenytoin but it might be a target for carbamazepine action.
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
18. Influence of flunarizine on hippocampal epileptic afterdischarges in the rat
- Creator:
- Pohl, M. and Mareš, P.
- Type:
- article, model:article, and TEXT
- Subject:
- epileptic afterdischarges, hippocampus, rat, and flunarizine
- Language:
- English
- Description:
- Epileptic afterdischarges elicited by electrical stimulation of the dorsal hippocampus in freely moving rats were not significantly changed by flunarizine administration in comparison with control sessions in which the animals received the solvent only. On the other hand, flunarizine significantly reduced the number of wet dog shakes, the main automatisms accompanying limbic afterdischarges.
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
19. Influence of phénobarbital on ECoG phenomena induced by metrazol in rats during ontogenesis
- Creator:
- Staňková, L. and Mareš, P.
- Type:
- article, model:article, and TEXT
- Subject:
- EEG, pentylenetetrazol, phénobarbital, ontogenesis, and rat
- Language:
- English
- Description:
- Effect of phénobarbital (PhB, 20 and/or 40 mg/kg) on epileptic ECoG phenomena induced by metrazol was studied in acute experiments in rats aged 7, 12, 18, 25 and 90 days. Fractionated administration of metrazol (20 mg/kg i.p. each 300 s) was used to quantify the effects of PhB. First signs of metrazol action (sharp elements and/or rhythmic metrazol activity) were not reliably influenced by PhB. On the contrary, the latency of the first EEG seizures as well as of the first generalized EEG seizures was prolonged and thus a dose necessary for their elicitation was increased in all age groups. These differences reached statistical significance in 12-, 18- and 25-day-old rats. A lack of effect of PhB against the rhythmic metrazol activity supports the adequacy of this activity as a model of human absences. Differences between the development of antiepileptic and hypnotic effects of PhB (described earlier) suggest two different mechanisms of action.
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
20. Influence of phenytoin and valproate on thalamocortical evoked potentials and their paired-pulse potentiation
- Creator:
- Mareš, P., Pohl, M., and Koryntová, H.
- Type:
- article, model:article, and TEXT
- Subject:
- thalamocortical responses, potentiation, rat, phenytoin, and valproate
- Language:
- English
- Description:
- The action of phenytoin and valproate on thalamocortical responses was studied in adult rats. Single responses were not influenced by either drug. Paired-pulse potentiation of the initial components (first positive and first negative) observed with intervals from 50 to 200 ms under control conditions was abolished by phenytoin (60 mg/kg i.p.) but only moderately influenced by valproate (400 mg/kg i.p.). Paired-pulse potentiation of thalamocortical phenomena cannot be put into connection with the generation of the spike-and-wave rhythm.
- Rights:
- http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public
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