RESUMEN
The effects of the novel proline-containing nootropic and neuroprotective dipeptide noopept (GVS-111, N-phenylacetyl-L-prolylglycine ethyl ester) were studied on NMRI mice upon olfactory bulbectomy, which had been previously shown to imitate the main morphological and biochemical signs of Alzheimer's disease (AD). The spatial memory was assessed using the Morris (water maze) test; the immunological status was characterized by ELISA with antibodies to prefibrillar beta-amyloid(25-35), S100b protein, and protofilaments of equine lysozyme, which are the molecular factors involved in the pathogenesis of AD. The control (sham-operated) animals during the Morris test preferred a sector where the safety platform was placed during the learning session. Bulbectomized animals treated with saline failed to recognize this sector, while bulbectomized animals treated with noopept (0.01 mg/kg for 21 days) restored this predominance, thus demonstrating the improvement of the spatial memory. These animals also demonstrated an increase in the level of antibodies to beta-amyloid(25-35)--the effect, which was more pronounced in the sham-operated than in bulbectomized mice. The latter demonstrated a profound decrease of immunological reactivity in a large number of tests. Noopept, stimulating the production of antibodies to beta-amyloid(25-35), can attenuate the well-known neurotoxic effects of beta-amyloid. The obtained data on the mnemotropic and immunostimulant effects noopept are indicative of good prospects for the clinical usage of this drug in the therapy of patients with neurodegenerative diseases.
Asunto(s)
Péptidos beta-Amiloides/inmunología , Anticuerpos/sangre , Dipéptidos/farmacología , Memoria/efectos de los fármacos , Fragmentos de Péptidos/inmunología , Conducta Espacial/efectos de los fármacos , Enfermedad de Alzheimer/tratamiento farmacológico , Animales , Dipéptidos/uso terapéutico , Modelos Animales de Enfermedad , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , RatonesRESUMEN
The effect of ladasten (50 mg/kg) on the activity of tyrosine hydrolase (TH) and DOPA-decarboxylase (DDC) gene expression and on the content of dopamine and L-DOPA in the striatum and hypothalamus in rat brain was studied depending on the duration of drug action. In the initial stage (first hours) of the drug action, the dopaminergic effects are related to an increase in the dopamine release. The observed accumulation of L-DOPA and dopamine is correlated with the transcription activity of genes studied. This leads to a conclusion that the pharmacological activity of ladasten is related to activation of de novo synthesis of TH and DDC. There is a certain difference in the ladasten action upon the TH and DDC gene expression of the key enzymes in hypothalamus and striatum of rat brain.
Asunto(s)
Adamantano/análogos & derivados , Adamantano/farmacología , Cuerpo Estriado/efectos de los fármacos , Dopamina/biosíntesis , Expresión Génica/efectos de los fármacos , Hipocampo/efectos de los fármacos , Animales , Animales no Consanguíneos , Cuerpo Estriado/química , Cuerpo Estriado/enzimología , Dopa-Decarboxilasa/análisis , Dopa-Decarboxilasa/genética , Dopamina/genética , Hipocampo/química , Hipocampo/enzimología , ARN Mensajero/análisis , ARN Mensajero/metabolismo , Ratas , Tirosina 3-Monooxigenasa/análisis , Tirosina 3-Monooxigenasa/genéticaRESUMEN
The effect of the new drug SM-346, a derivative of 2-mercaptobenzimidazole, on the behavior of inbred MR and MNRA rats, differing in the phenotype of the emotional-stress reaction in the open field test was studies. In the Vogel conflict test SM-346 in a dose of 1 mg/kg produced an anxiolytic effect in MR rats but had no effect on the behavior of MNRA rats. The obtained results allow the conclusion that SM-346 possesses a selective anxiolytic action.
Asunto(s)
Ansiolíticos/toxicidad , Antimetabolitos/toxicidad , Ansiedad/inducido químicamente , Conducta Animal/efectos de los fármacos , Bencimidazoles/toxicidad , Administración Oral , Animales , Ansiolíticos/administración & dosificación , Ansiolíticos/farmacología , Antimetabolitos/administración & dosificación , Antimetabolitos/metabolismo , Bencimidazoles/administración & dosificación , Bencimidazoles/uso terapéutico , Diazepam/administración & dosificación , Diazepam/farmacología , Masculino , Fenotipo , Ratas , Ratas Endogámicas , Estándares de Referencia , Especificidad de la Especie , Estrés Psicológico/fisiopatologíaRESUMEN
The method of chromosome aberration scoring in the bone marrow cells of C57BL/6 mice was used to study the influence of apo-carotene (AC) on the clastogenic effect of intraperitoneal injections of the following two mutagens: cyclophosphamide (CP) in a dose of 30 mg/kg and dioxidine (DN) in a dose of 300 mg/kg. AC was given per os as a food dye E160L (20% oil suspension) in doses of 0.5, 5, and 50 mg/kg (0.1, 1.0 and 10 mg/kg, respectively, on conversion to pure apo-carotene). The experiment was conducted in three variants: in simultaneous injection of the compounds for 24 h, injection of the mutagens for 24 h in 5-day treatment of the animals with AC, and in combined 5-day administration of AC and mutagens and killing of the animals 6 h after the last administration. In all variants a 10 mg/kg dose of AC reduced the clastogenic effect of CP and DN. Moreover, the clastogenic effect of CP was reduced in pretreatment of the animals with AC in a dose of 1 mg/kg, and that of DN when it was combined with AC in a dose of 0.1 mg/kg for 5 days and in pretreatment of the animals with AC in a dose of 1.0 mg/kg.
Asunto(s)
Médula Ósea/efectos de los fármacos , Carotenoides/farmacología , Aberraciones Cromosómicas/genética , Ciclofosfamida/toxicidad , Mutágenos/toxicidad , Quinoxalinas/toxicidad , Animales , Células de la Médula Ósea , Carotenoides/administración & dosificación , Ciclofosfamida/administración & dosificación , Interacciones Farmacológicas , Inyecciones Intraperitoneales , Masculino , Ratones , Ratones Endogámicos C57BL , Mutación/efectos de los fármacos , Mutación/genética , Quinoxalinas/administración & dosificaciónRESUMEN
Blood plasma content of cAMP and cGMP in C57BL/6, BALB/c mice and their reciprocal F1-hybrids has been studied at rest, upon exposure to stress induced in an open field technique and phenazepam injection at a dose of 0.05 and 0.1 mg/kg. Interstrain differences in baseline content and changes of nucleotide concentration in conditions of stress have been revealed. F1-hybrids inherit initial correlation between nucleotide content and the type of cAMP changes of C57BL/6 mice and cGMP changes of BALB/c mice. Phenazepam injection to C57BL/6 and BALB/c mice was shown to produce specific shifts in blood plasma cyclic nucleotide content.