RESUMEN
A seizure-protecting effect of the delta-sleep-inducing peptide (DSIP) and its analogues was revealed. An intensive sorption of H3 tryptophan occurred under the effect of the DSIP and its analogues. The data obtained suggests that the serotoninergic system plays no important part in the seizure-protecting effect.
Asunto(s)
Anticonvulsivantes/farmacología , Péptido Inductor del Sueño Delta/análogos & derivados , Péptido Inductor del Sueño Delta/farmacología , Receptores de Serotonina/efectos de los fármacos , Animales , Anticonvulsivantes/administración & dosificación , Convulsivantes , Péptido Inductor del Sueño Delta/administración & dosificación , Evaluación Preclínica de Medicamentos , Epilepsia Generalizada/inducido químicamente , Epilepsia Generalizada/tratamiento farmacológico , Hipocampo/efectos de los fármacos , Hipocampo/fisiología , Ácido Kaínico , Masculino , Picrotoxina , Ratas , Ratas Wistar , Receptores de Serotonina/fisiología , Sustancia Negra/efectos de los fármacos , Sustancia Negra/fisiología , Tritio , Triptófano/metabolismoRESUMEN
The ED100 of the NMDA inducing clonic seizures (0.53 mcg) or tonic extension of forelimbs (5.02 mcg) increased their efficiency 2.3-fold and 4.46-fold, resp., due to the delta-sleep-inducing peptide administration in rats. The data obtained suggests a neuroprotective effect of the peptide on agonists of excitatory amino acid receptors action.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Péptido Inductor del Sueño Delta/uso terapéutico , Convulsiones/tratamiento farmacológico , Animales , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Agonistas de Aminoácidos Excitadores/administración & dosificación , Inyecciones Intraperitoneales , Inyecciones Intraventriculares , Microinyecciones , N-Metilaspartato/administración & dosificación , Ratas , Ratas Wistar , Convulsiones/inducido químicamenteRESUMEN
The effects of delta-sleep inducing peptide (DSIP) and its analogues (1-4) administered into substantia nigra pars reticulata on locomotor and seizure activity were estimated in experiments in rats. It was shown that intranigral microinjection of DSIP as well as DSIP-1-DSIP-4 caused decreasing of horizontal, vertical locomotor activity and attendance of central sectors of the "open field". Antiseizure effects, i.e. the first and clonic-tonic picrotoxin-induced convulsive latent period lengthening and their intensity decreasing, revealed DSIP, DSIP-2 and DSIP-3. Authors suppose that changes of DSIP structure lead to changes of effects expression on locomotor and seizure activity in conditions of their administration into substantia nigra reticulata. Obtained data concerning protective effects of studied peptides on experimental seizure syndrome allow to conclude that there is interaction between DSIP-induced hypokinesia and DSIP analogues anticonvulsive effectiveness in case of their intranigral administration which is likelihood is one of the component of nigral-dependent seizure-suppressive mechanism.
Asunto(s)
Anticonvulsivantes/farmacología , Péptido Inductor del Sueño Delta/análogos & derivados , Péptido Inductor del Sueño Delta/farmacología , Actividad Motora/efectos de los fármacos , Convulsiones/tratamiento farmacológico , Animales , Anticonvulsivantes/administración & dosificación , Péptido Inductor del Sueño Delta/administración & dosificación , Evaluación Preclínica de Medicamentos , Masculino , Microinyecciones , Actividad Motora/fisiología , Picrotoxina , Ratas , Ratas Wistar , Tiempo de Reacción/efectos de los fármacos , Tiempo de Reacción/fisiología , Convulsiones/inducido químicamente , Convulsiones/fisiopatología , Sustancia NegraAsunto(s)
Péptido Inductor del Sueño Delta/fisiología , Epilepsia/fisiopatología , Animales , Anticonvulsivantes/uso terapéutico , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Encéfalo/efectos de los fármacos , Encéfalo/fisiopatología , Péptido Inductor del Sueño Delta/farmacología , Péptido Inductor del Sueño Delta/uso terapéutico , Evaluación Preclínica de Medicamentos , Epilepsia/tratamiento farmacológico , Excitación Neurológica/efectos de los fármacos , Excitación Neurológica/fisiología , Convulsiones/tratamiento farmacológico , Convulsiones/fisiopatología , Estrés Psicológico/fisiopatologíaRESUMEN
The delta-sleep-inducing peptide (DSIP) suppressed seizure activity in the cat cortical strychnine-induced seizure foci. The DSIP delayed development of corazol kindling in rats, prevented seizure induced with bicucullin and other agents in mice. The DSIP effect was shown to be realised through the action upon reticular black substance. The DSIP seems to take part in endogenous control of the brain excitability.
Asunto(s)
Péptido Inductor del Sueño Delta/uso terapéutico , Convulsiones/tratamiento farmacológico , Animales , Química Encefálica/efectos de los fármacos , Gatos , Péptido Inductor del Sueño Delta/administración & dosificación , Péptido Inductor del Sueño Delta/análisis , Evaluación Preclínica de Medicamentos , Electroencefalografía/efectos de los fármacos , Excitación Neurológica/efectos de los fármacos , Excitación Neurológica/fisiología , Masculino , Mesencéfalo/química , Mesencéfalo/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Ratas , Ratas Wistar , Convulsiones/inducido químicamente , Convulsiones/metabolismo , Factores de TiempoRESUMEN
The antiepileptic action of neurotropin (Nippon Zoki Pharmaceutied Co. Ltd., Japan) was investigated in acute experiments on rats, mice and cats. The increasing of latent period of the first seizures which were picrotoxin-induced and enhancing of this type of seizures were observed correspondently in 1-24 hours and 8-9 days after intraventricular neurotropin injection. Intraperitoneal neurotropin injection (0.2-0.5 ml) to mice caused dosage-dependent antiseizure action on the model of generalized picrotoxin-induced seizures. +Anticonvulsant++ effect of neurotropin was observed during five days. The intraventricular neurotropin injection to cats led to strychnine (0.1%) induced cortical foci suppression.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Modelos Animales de Enfermedad , Epilepsia/tratamiento farmacológico , Polisacáridos/uso terapéutico , Animales , Anticonvulsivantes/administración & dosificación , Gatos , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Epilepsia/inducido químicamente , Ratones , Picrotoxina , Polisacáridos/administración & dosificación , Ratas , Ratas EndogámicasRESUMEN
Intraventricular injection of cerebrospinal fluid (CSF) obtained from cats with chronic electrical stimulation of cerebellar vermal cortex resulted in suppression of epileptic foci activity in cat brain cortex, an increase in time to first seizure, and weakening of generalized seizures in rats. The CSF obtained from cats after electroshock seizures induced less pronounced, although significant antiepileptic action in comparison with the CSF of cats with cerebellar stimulation on the model of generalized seizures in rats. The antiepileptic action of CSF obtained from cats with electrostimulation of cerebellar vermis and from electroshock cats is due to appearance of peptide factors in CSF.
Asunto(s)
Anticonvulsivantes , Cerebelo/fisiología , Líquido Cefalorraquídeo/fisiología , Epilepsia/prevención & control , Animales , Gatos , Líquido Cefalorraquídeo/análisis , Estimulación Eléctrica , Electrochoque , Epilepsia/etiología , Femenino , Inyecciones Intraventriculares , Masculino , Pentilenotetrazol/efectos adversos , Péptidos/análisis , Péptidos/farmacología , Ratas , Ratas Endogámicas , Factores de TiempoRESUMEN
The influence of delta-sleep inducing peptide (DSIP) upon seizures induced by corazol, bicuculline, picrotoxin, strychnine, thiosemicarbazide were investigated in experiments on F1(CBA X C57 BL/6) mice. It was shown that DSIP increased the latency of first seizure manifestation which were induced by corazol, bicuculline and picrotoxin and also resulted in a suppression of seizure severity of corazol and bicuculline induced seizures. Anticonvulsant action of DSIP was evident under the condition of the mild severity seizures development. The effect of DSIP was mostly pronounced in range of its doses from 10 to 100 mcg/kg. DSIP when combined with phenobarbital, carbamazepine, diphenylhydantoin or nicotinamide enhanced the antiepileptic effects of these anticonvulsant drugs.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Péptido Inductor del Sueño Delta/uso terapéutico , Niacinamida/uso terapéutico , Convulsiones/tratamiento farmacológico , Animales , Convulsivantes/farmacología , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Tiempo de Reacción/efectos de los fármacos , Convulsiones/inducido químicamenteRESUMEN
The experiments on rats have shown that bilateral administration of kainic acid (0.1-0.15 microgram) into the rostral parts of caudate nuclei led to the development of hypokinesia and rigidity. An increase in the electrical activity--the formation of the generator of pathologically increased excitement (GPIE) was noted in a zone of kainic acid injection. Rigidity and hypokinesia were attenuated and the GPIE activity was depressed after cyclodol (1-10 mg/kg) or L-DOPA (100-200 mg/kg) administration. Combined administration of cyclodol (2 mg/kg) and L-DOPA (50 mg/kg) induced potentiated antiparkinsonian effect. Dopamine microinjections into the GPIE area depressed its activity and abolished rigidity and hypokinesia. These data suggest that the Parkinson syndrome develops under the influence of GPIE induced by kainic acid administration into caudate nuclei.
Asunto(s)
Modelos Animales de Enfermedad , Ácido Kaínico/farmacología , Enfermedad de Parkinson Secundaria/inducido químicamente , Animales , Núcleo Caudado , Evaluación Preclínica de Medicamentos , Electrodos Implantados , Electroencefalografía , Femenino , Inyecciones , Levodopa/uso terapéutico , Masculino , Enfermedad de Parkinson Secundaria/tratamiento farmacológico , Ratas , Factores de Tiempo , Trihexifenidilo/uso terapéuticoRESUMEN
Acute experiments on mice were made to investigate the anticonvulsant activity of diazepam and its combination with nicotinamide in experimental seizures induced by corazol, picrotoxin, bicucullin and thiosemicarbazide. It was shown that diazepam (0.2-1.6 mg/kg) produced a dose-dependent anticonvulsant effect in all models under study. Nicotinamide (250 mg/kg) substantially reduced the animals' lethality and seizure manifestations induced by picrotoxin and completely protected some of the animals from the bicucullin-induced seizures. Nicotinamide (250 mg/kg) potentiated the anticonvulsant effect of diazepam in all the experimental seizures under study. Micotinamide had a more pronounced effect in respect of the protection of the animals from tonic seizures as compared with clonic ones. The data suggest that the mechanisms of the anticonvulsant action of nicotinamide are mediated via the GABA-benzodiazepine receptor complex.
Asunto(s)
Diazepam/uso terapéutico , Niacinamida/uso terapéutico , Convulsiones/tratamiento farmacológico , Animales , Convulsivantes/toxicidad , Evaluación Preclínica de Medicamentos , Sinergismo Farmacológico , Quimioterapia Combinada , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Convulsiones/inducido químicamente , Factores de TiempoRESUMEN
It has been shown in experiments on mice and rats that daily administration of subthreshold doses of pentylenetetrazol led to a progressive increase in the sensitivity to the action of the epileptogen, augmentation of brain epileptization and development of the pharmacological kindling. Single administration of nicotinamide in doses of 250, 500 and 1000 mg/kg and alpha-tocopherol in a dose of 100 mg/kg exerted a pronounced antiepileptic effect under the conditions of over kindling. On combined use of nicotinamide and pyridoxal-5-phosphate, nicotinamide, pyridoxal-5-phosphate and alpha-tocopherol the antiepileptic action was more demonstrable. Daily administration of a complex of the drugs (nicotinamide, pyridoxal-5-phosphate, alpha-tocopherol) produced a substantial reduction in epileptic activity under the conditions of overt kindling. The possibility has been demonstrated of preventing the development of epileptic activity with nicotinamide under kindling.
Asunto(s)
Epilepsia/tratamiento farmacológico , Vitaminas/uso terapéutico , Animales , Evaluación Preclínica de Medicamentos , Quimioterapia Combinada , Epilepsia/prevención & control , Excitación Neurológica/efectos de los fármacos , Ratones , Niacinamida/uso terapéutico , Fosfato de Piridoxal/uso terapéutico , Ratas , Convulsiones/tratamiento farmacológico , Convulsiones/prevención & control , Vitamina E/uso terapéuticoRESUMEN
It was shown in acute experiments on mice that nicotinamide in doses of 250-500 mg/kg given intraperitoneally increased the latent period of corasole clonico-tonic convulsions without affecting their expressiveness and mortality. When given in a dose of 1000 mg/kg nicotinamide prevented clonico-tonic convulsions and mortality, and considerably raised the latent period of convulsions and the lifespan of the animals intoxicated with thiosemicarbazide and strychnine. The expressiveness of the nicotinamide effects depended on the time of its administration.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Niacinamida/uso terapéutico , Convulsiones/tratamiento farmacológico , Animales , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Ratones , Tiempo de Reacción/efectos de los fármacos , Convulsiones/inducido químicamente , Factores de Tiempo , Ácido gamma-Aminobutírico/uso terapéuticoRESUMEN
It was shown in experiments on cats that electrostimulation (ES) of the nucleus caudalis reticularis pontis under the destruction of the central grey matter suppressed discharges in a single epileptic focus, created with application of strychnine to the brain cortex and did not suppress the epileptic activity in the complex of foci, formed under the influence of a determinant focus after local application of strychnine to different zones of the neocortex. After increasing the number of foci in the complex the resistance of the latter to suppressive effects of ES of the nucleus caudalis increases too. The complex reduction owing to liquidation of its foci (local application of nembutal) facilitates the suppressive effects of ES of the nucleus caudalis. Under prolonged inhibition of the epileptic activity in the focus, the coagulation of the nucleus caudalis leads after its long-term ES to the recovery of the epileptic activity. The evidence obtained is discussed from the standpoint of the properties of the pathological system (epileptic complex) and the role of the "antisystem" in suppression of its activity.