7 research outputs found
ΠΡΠΎΠ±Π°Π·ΠΎΠ» ΠΎΡΠ»Π°Π±Π»ΡΠ΅Ρ ΠΈΠ½Π΄ΡΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ ΡΡΠ°Π½ΠΎΠ»ΠΎΠΌ ΠΏΠΎΠ²Π΅Π΄Π΅Π½ΡΠ΅ΡΠΊΡΡ ΡΠ΅Π½ΡΠΈΠ±ΠΈΠ»ΠΈΠ·Π°ΡΠΈΡ Ρ ΠΌΡΡΠ΅ΠΉ DBA/2
Resume. Background. Adverse medical and social consequences of alcohol abuse determine the relevance of the search for new targets and methods of effective prevention and treatment of alcoholism. A significant limitation of the use of benzodiazepine anxiolytics in the treatment of alcohol disorders is their ability to potentiate the effects of ethanol. Earlier it was found that the original afobazol, effective in the treatment of anxiety disorders, in the range of anxiolytic doses does not affect the duration of alcoholic sleep and ethanol-induced muscle relaxation. The aim of the present work was to investigate the effects of afobazole on hyperlocomotion and expression of behavioral sensitization induced by ethanol. Methods. The effect of afobazole at the doses 1.0 and 10.0 mg/kg, i.p., on the ethanol-induced hyperlocomotion and behavioral sensitization was assessed in actometer OPTO-VARIMEX in male DBA/2 mice with increased sensitivity to the activating effect of ethanol. Results. Afobazole at a dose of 10.0 mg/kg, but not 1.0 mg/kg after acute administration prevented the development of ethanol-induced (2.0 g/kg, i.p.) hyperlocomotion, like naloxone 1.0 mg/kg, i.p., and antagonized ethanol-induced behavioral sensitization. Conclusion. Thus, the data obtained suggest that afobazole is capable of modeling the motivational effects of ethanol.ΠΠΊΡΡΠ°Π»ΡΠ½ΠΎΡΡΡ. ΠΠ΅Π±Π»Π°Π³ΠΎΠΏΡΠΈΡΡΠ½ΡΠ΅ ΠΌΠ΅Π΄ΠΈΡΠΈΠ½ΡΠΊΠΈΠ΅ ΠΈ ΡΠΎΡΠΈΠ°Π»ΡΠ½ΡΠ΅ ΠΏΠΎΡΠ»Π΅Π΄ΡΡΠ²ΠΈΡ Π·Π»ΠΎΡΠΏΠΎΡΡΠ΅Π±Π»Π΅Π½ΠΈΡ Π°Π»ΠΊΠΎΠ³ΠΎΠ»Π΅ΠΌ ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΡΡ Π°ΠΊΡΡΠ°Π»ΡΠ½ΠΎΡΡΡ ΠΏΠΎΠΈΡΠΊΠ° Π½ΠΎΠ²ΡΡ
ΡΡΠ΅Π΄ΡΡΠ² ΠΈ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠΉ ΠΏΡΠΎΡΠΈΠ»Π°ΠΊΡΠΈΠΊΠΈ ΠΈ Π»Π΅ΡΠ΅Π½ΠΈΡ Π°Π»ΠΊΠΎΠ³ΠΎΠ»ΠΈΠ·ΠΌΠ°. ΠΠ½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΡΠΌ ΠΎΠ³ΡΠ°Π½ΠΈΡΠ΅Π½ΠΈΠ΅ΠΌ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΡ Π±Π΅Π½Π·ΠΎΠ΄ΠΈΠ°Π·Π΅ΠΏΠΈΠ½ΠΎΠ²ΡΡ
Π°Π½ΠΊΡΠΈΠΎΠ»ΠΈΡΠΈΠΊΠΎΠ² Π² ΡΠ΅ΡΠ°ΠΏΠΈΠΈ Π°Π»ΠΊΠΎΠ³ΠΎΠ»ΡΠ½ΡΡ
ΡΠ°ΡΡΡΡΠΎΠΉΡΡΠ² ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΈΡ
ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΡ ΠΏΠΎΡΠ΅Π½ΡΠΈΡΠΎΠ²Π°ΡΡ ΡΡΡΠ΅ΠΊΡΡ ΡΡΠ°Π½ΠΎΠ»Π°. Π Π°Π½Π΅Π΅ ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ ΠΎΡΠΈΠ³ΠΈΠ½Π°Π»ΡΠ½ΡΠΉ ΠΎΡΠ΅ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΠΉ ΠΏΡΠ΅ΠΏΠ°ΡΠ°Ρ Π°ΡΠΎΠ±Π°Π·ΠΎΠ», ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΡΠΉ ΠΏΡΠΈ Π»Π΅ΡΠ΅Π½ΠΈΠΈ ΡΡΠ΅Π²ΠΎΠΆΠ½ΡΡ
ΡΠ°ΡΡΡΡΠΎΠΉΡΡΠ², Π² Π΄ΠΈΠ°ΠΏΠ°Π·ΠΎΠ½Π΅ Π°Π½ΠΊΡΠΈΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π΄ΠΎΠ· Π½Π΅ Π²Π»ΠΈΡΠ΅Ρ Π½Π° ΠΏΡΠΎΠ΄ΠΎΠ»ΠΆΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΡ Π°Π»ΠΊΠΎΠ³ΠΎΠ»ΡΠ½ΠΎΠ³ΠΎ Π½Π°ΡΠΊΠΎΠ·Π° ΠΈ Π²ΡΠ·ΡΠ²Π°Π΅ΠΌΡΡ ΡΡΠ°Π½ΠΎΠ»ΠΎΠΌ ΠΌΠΈΠΎΡΠ΅Π»Π°ΠΊΡΠ°ΡΠΈΡ. Π¦Π΅Π»Ρ. ΠΠ·ΡΡΠ΅Π½ΠΈΠ΅ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ Π°ΡΠΎΠ±Π°Π·ΠΎΠ»Π° Π½Π° Π³ΠΈΠΏΠ΅ΡΠ»ΠΎΠΊΠΎΠΌΠΎΡΠΎΡΠ½ΡΡ ΡΠ΅Π°ΠΊΡΠΈΡ ΠΈ ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΠ΅ ΠΏΠΎΠ²Π΅Π΄Π΅Π½ΡΠ΅ΡΠΊΠΎΠΉ ΡΠ΅Π½ΡΠΈΠ±ΠΈΠ»ΠΈΠ·Π°ΡΠΈΠΈ, ΠΈΠ½Π΄ΡΡΠΈΡΠΎΠ²Π°Π½Π½ΡΠ΅ ΡΡΠ°Π½ΠΎΠ»ΠΎΠΌ. ΠΠ΅ΡΠΎΠ΄Ρ. Π ΠΎΠΏΡΡΠ°Ρ
in vivo Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ Π°ΠΊΡΠΎΠΌΠ΅ΡΡΠ° OPTO-VARIMEX 4 ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΎ Π²Π»ΠΈΡΠ½ΠΈΠ΅ Π°ΡΠΎΠ±Π°Π·ΠΎΠ»Π° Π² Π΄ΠΎΠ·Π°Ρ
1,0 ΠΈ 10,0 ΠΌΠ³/ΠΊΠ³, Π²/Π±, Π½Π° ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΡΡ ΡΡΠ°Π½ΠΎΠ»ΠΎΠΌ Π² Π΄ΠΎΠ·Π΅ 2,0 Π³/ΠΊΠ³, Π²/Π±, ΡΡΠΈΠΌΡΠ»ΡΡΠΈΡ ΠΏΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ ΠΈ ΡΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½Π½ΡΡ ΠΏΠΎΠ²Π΅Π΄Π΅Π½ΡΠ΅ΡΠΊΡΡ ΡΠ΅Π½ΡΠΈΠ±ΠΈΠ»ΠΈΠ·Π°ΡΠΈΡ Ρ ΠΈΠ½Π±ΡΠ΅Π΄Π½ΡΡ
ΠΌΡΡΠ΅ΠΉ Π»ΠΈΠ½ΠΈΠΈ DBA/2, ΠΎΠ±Π»Π°Π΄Π°ΡΡΠΈΡ
ΠΏΠΎΠ²ΡΡΠ΅Π½Π½ΠΎΠΉ ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΡΡ ΠΊ Π°ΠΊΡΠΈΠ²ΠΈΡΡΡΡΠ΅ΠΌΡ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ ΡΡΠ°Π½ΠΎΠ»Π°. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΡΠΎΠ±Π°Π·ΠΎΠ» Π² Π΄ΠΎΠ·Π΅ 10,0 ΠΌΠ³/ΠΊΠ³, Π½ΠΎ Π½Π΅ 1,0 ΠΌΠ³/ΠΊΠ³ ΠΏΡΠΈ ΠΎΠ΄Π½ΠΎΠΊΡΠ°ΡΠ½ΠΎΠΌ Π²Π²Π΅Π΄Π΅Π½ΠΈΠΈ ΠΏΡΠ΅Π΄ΡΠΏΡΠ΅ΠΆΠ΄Π°Π» ΡΡΠ°Π½ΠΎΠ»-ΠΈΠ½Π΄ΡΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ Π³ΠΈΠΏΠ΅ΡΠ»ΠΎΠΊΠΎΠΌΠΎΡΠΎΡΠ½ΡΡ ΡΠ΅Π°ΠΊΡΠΈΡ, ΠΏΠΎΠ΄ΠΎΠ±Π½ΠΎ Π½Π°Π»ΠΎΠΊΡΠΎΠ½Ρ 1,0 ΠΌΠ³/ΠΊΠ³, Π²/Π±, ΠΈ ΠΏΡΠ΅ΠΏΡΡΡΡΠ²ΠΎΠ²Π°Π» ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΡ Π²ΡΠ·ΡΠ²Π°Π΅ΠΌΠΎΠΉ ΡΡΠ°Π½ΠΎΠ»ΠΎΠΌ ΠΏΠΎΠ²Π΅Π΄Π΅Π½ΡΠ΅ΡΠΊΠΎΠΉ ΡΠ΅Π½ΡΠΈΠ±ΠΈΠ»ΠΈΠ·Π°ΡΠΈΠΈ. ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠΎΠ»ΡΡΠ΅Π½Π½ΡΠ΅ Π΄Π°Π½Π½ΡΠ΅ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΡΡ ΠΏΡΠ΅Π΄ΠΏΠΎΠ»ΠΎΠΆΠΈΡΡ ΠΌΠΎΠ΄ΡΠ»ΠΈΡΡΡΡΠ΅Π΅ Π²Π»ΠΈΡΠ½ΠΈΠ΅ Π°ΡΠΎΠ±Π°Π·ΠΎΠ»Π° Π½Π° ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π°Π»ΠΊΠΎΠ³ΠΎΠ»ΡΠ½ΠΎΠΉ ΠΌΠΎΡΠΈΠ²Π°ΡΠΈΠΈ ΠΏΡΠΈ ΠΌΠΎΠ΄Π΅Π»ΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΠΎΠ³ΠΎ Π°Π»ΠΊΠΎΠ³ΠΎΠ»ΠΈΠ·ΠΌΠ°
Glyproline Pro-Ampakine with Neuroprotective Activity
Previously it was shown that neuropeptide cyclo-L-prolylglycine (CPG) is a positive modulator of AMPA receptors, which increases BDNF level in neuronal cell cultures. The spectrum of CPGβs pharmacological effects corresponds to that of BDNF. Dipeptide N-phenylacetyl-glycyl-L-proline ethyl ester (GZK-111) was designed and synthesized as a linear analog of CPG. The aim of the present work was to reveal the pharmacological profile of GZK-111. Dipeptide GZK-111 was shown to metabolize into CPG in vitro and increased cell survival by 28% at concentrations of 10-7β10-6 M in a Parkinsonβs disease cell model. In a model of cerebral ischemia, GZK-111, at a dose of 0.5 mg/kg, i.p., was found to have neuroprotective effects, reducing the cerebral infarct volume by 1.6 times. Similar to CPG, GZK-111, at the range 0.1β1.0 mg/kg, i.p., possessed a stereospecific antiamnesic activity. A significant anxiolytic effect was observed at a dose of 1.5 mg/kg. GZK-111, at the range 0.5β4.0 mg/kg, i.p., demonstrated analgesic activity. GZK-111, at a dose of 10 mg/kg/7 days, i.p., possessed antidepressant-like activity. So, the neuroprotective, nootropic, antihypoxic, anxiolytic, antidepressant-like, and analgesic effects of GZK-111 were revealed. Thus, GZK-111 can be considered as a pharmacologically active pro-ampakine with a BDNF-ergic mechanism of action
ΠΠ»ΠΈΡΠ½ΠΈΠ΅ ΡΠ΅Π»Π°Π½ΠΊΠ° Π½Π° ΠΌΠΎΡΡΠΈΠ½-ΠΈΠ½Π΄ΡΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ Π°Π½Π°Π»ΡΠ³Π΅Π·ΠΈΡ Π² ΠΎΠΏΡΡΠ°Ρ in vivo
Β Β Background.Β The endogenous opioid system is involved in neuroadaptation produced by exogenous opioids. Synthesized on the basis of the regulatory peptide tuftsin, the anxiolytic selank inhibits the activity of enkephalin-degrading enzymes, increasing the level of leu-enkephalins in blood plasma.Β Β The aim of the workΒ was to evaluate the effect of selank (0,3 and 0,9 mg/kg, i. p.) on morphine-induced analgesia in animal models. Methods. The experiments were performed in inbred male mice C57Bl/6 (n = 77). The βhot plateβ test was used to evaluate the analgesic effect during thermal stimulation of nociceptors when mice were placed on a metal plate heated to 55 Β± 0,5 Β°C, followed by registration of the latent period of the reaction 30, 60, 90, and 120 minutes after the administration of morphine.Β Β Results.Β Morphine at a dose of 3,0 mg/kg, i. p., caused antinociception with the maximum possible effect (MBE) of 9 %, selank at a dose of 0,9 mg/kg, without antinociception per se, when pretreated with the morphine, increased the latent reaction time, causing antinociception of 29,9 % MBE.Β Β Conclusion.Β For the first time the data obtained on the synergistic effect of selank and morphine in attenuation of acute somatic pain.Β Β ΠΠΊΡΡΠ°Π»ΡΠ½ΠΎΡΡΡ. ΠΠ½Π΄ΠΎΠ³Π΅Π½Π½Π°Ρ ΠΎΠΏΠΈΠΎΠΈΠ΄Π½Π°Ρ ΡΠΈΡΡΠ΅ΠΌΠ° Π²ΠΎΠ²Π»Π΅ΡΠ΅Π½Π° Π² ΠΏΡΠΎΡΠ΅ΡΡΡ Π½Π΅ΠΉΡΠΎΠ°Π΄Π°ΠΏΡΠ°ΡΠΈΠΈ ΠΏΡΠΈ Π΄Π΅ΠΉΡΡΠ²ΠΈΠΈ ΡΠΊΠ·ΠΎΠ³Π΅Π½Π½ΡΡ
ΠΎΠΏΠΈΠΎΠΈΠ΄ΠΎΠ². Π‘ΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½Π½ΡΠΉ Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠ½ΠΎΠ³ΠΎ ΠΏΠ΅ΠΏΡΠΈΠ΄Π° ΡΠ°ΡΡΡΠΈΠ½Π° Π°Π½ΠΊΡΠΈΠΎΠ»ΠΈΡΠΈΠΊ ΡΠ΅Π»Π°Π½ΠΊ ΡΠ³Π½Π΅ΡΠ°Π΅Ρ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΡΠ½ΠΊΠ΅ΡΠ°Π»ΠΈΠ½-Π΄Π΅Π³ΡΠ°Π΄ΠΈΡΡΡΡΠΈΡ
ΡΠ΅ΡΠΌΠ΅Π½ΡΠΎΠ², ΠΏΠΎΠ²ΡΡΠ°Ρ ΡΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅ Π»Π΅ΠΉ-ΡΠ½ΠΊΠ΅ΡΠ°Π»ΠΈΠ½ΠΎΠ² Π² ΠΏΠ»Π°Π·ΠΌΠ΅ ΠΊΡΠΎΠ²ΠΈ.Β Β Π¦Π΅Π»Ρ ΡΠ°Π±ΠΎΡΡ. ΠΡΠ΅Π½ΠΈΡΡ Π²Π»ΠΈΡΠ½ΠΈΠ΅ ΡΠ΅Π»Π°Π½ΠΊΠ° (0,3 ΠΈ 0,9 ΠΌΠ³/ΠΊΠ³, Π²/Π±) Π½Π° ΠΌΠΎΡΡΠΈΠ½-ΠΈΠ½Π΄ΡΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ Π°Π½Π°Π»ΡΠ³Π΅Π·ΠΈΡ Π² ΠΎΠΏΡΡΠ°Ρ
in vivo.Β Β ΠΠ΅ΡΠΎΠ΄Ρ. ΠΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΡ Π²ΡΠΏΠΎΠ»Π½Π΅Π½Ρ Π½Π° ΠΈΠ½Π±ΡΠ΅Π΄Π½ΡΡ
ΠΌΡΡΠ°Ρ
-ΡΠ°ΠΌΡΠ°Ρ
Π»ΠΈΠ½ΠΈΠΈ Π‘57Bl/6 (n = 77). Π’Π΅ΡΡ Β«Π³ΠΎΡΡΡΠ°Ρ ΠΏΠ»Π°ΡΡΠΈΠ½Π°Β» ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π»ΠΈ Π΄Π»Ρ ΠΎΡΠ΅Π½ΠΊΠΈ Π°Π½Π°Π»ΡΠ³Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² ΠΏΡΠΈ ΡΠ΅ΡΠΌΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΡΠΈΠΌΡΠ»ΡΡΠΈΠΈ Π½ΠΎΡΠΈΡΠ΅ΠΏΡΠΎΡΠΎΠ² ΠΏΡΠΈ ΠΏΠΎΠΌΠ΅ΡΠ΅Π½ΠΈΠΈ ΠΌΡΡΠ΅ΠΉ Π½Π° Π½Π°Π³ΡΠ΅ΡΡΡ Π΄ΠΎ 55 Β± 0,5 Β°Π‘ ΠΌΠ΅ΡΠ°Π»Π»ΠΈΡΠ΅ΡΠΊΡΡ ΠΏΠ»Π°ΡΡΠΈΠ½Ρ Ρ ΠΏΠΎΡΠ»Π΅Π΄ΡΡΡΠ΅ΠΉ ΡΠ΅Π³ΠΈΡΡΡΠ°ΡΠΈΠ΅ΠΉ Π»Π°ΡΠ΅Π½ΡΠ½ΠΎΠ³ΠΎ ΠΏΠ΅ΡΠΈΠΎΠ΄Π° ΡΠ΅Π°ΠΊΡΠΈΠΈ ΡΠ΅ΡΠ΅Π· 30, 60, 90 ΠΈ 120 ΠΌΠΈΠ½ ΠΏΠΎΡΠ»Π΅ Π²Π²Π΅Π΄Π΅Π½ΠΈΡ ΠΌΠΎΡΡΠΈΠ½Π°.Β Β Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΠΎΡΡΠΈΠ½ Π² Π΄ΠΎΠ·Π΅ 3,0 ΠΌΠ³/ΠΊΠ³, Π²/Π±, Π²ΡΠ·ΡΠ²Π°Π» Π°Π½ΡΠΈΠ½ΠΎΡΠΈΡΠ΅ΠΏΡΠΈΡ Ρ ΠΌΠ°ΠΊΡΠΈΠΌΠ°Π»ΡΠ½ΠΎ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΡΠΌ ΡΡΡΠ΅ΠΊΡΠΎΠΌ (MΠΠ) 9 %, ΡΠ΅Π»Π°Π½ΠΊ Π² Π΄ΠΎΠ·Π΅ 0,9 ΠΌΠ³/ΠΊΠ³, Π½Π΅ ΠΎΠ±Π»Π°Π΄Π°Ρ Π°Π½ΡΠΈΠ½ΠΎΡΠΈΡΠ΅ΠΏΡΠΈΠ²Π½ΡΠΌΠΈ ΡΠ²ΠΎΠΉΡΡΠ²Π°ΠΌΠΈ per se, ΠΏΡΠΈ ΠΏΡΠ΅Π΄Π²Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎΠΌ Π²Π²Π΅Π΄Π΅Π½ΠΈΠΈ Ρ ΠΌΠΎΡΡΠΈΠ½ΠΎΠΌ ΡΠ²Π΅Π»ΠΈΡΠΈΠ²Π°Π» Π»Π°ΡΠ΅Π½ΡΠ½ΡΠΉ ΠΏΠ΅ΡΠΈΠΎΠ΄ ΡΠ΅Π°ΠΊΡΠΈΠΈ, Π²ΡΠ·ΡΠ²Π°Ρ Π°Π½ΡΠΈΠ½ΠΎΡΠΈΡΠ΅ΠΏΡΠΈΡ Ρ ΠΠΠ 29,9 %.Β Β ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠΏΠ΅ΡΠ²ΡΠ΅ ΠΏΠΎΠ»ΡΡΠ΅Π½Ρ Π΄Π°Π½Π½ΡΠ΅ ΠΎ ΡΠΈΠ½Π΅ΡΠ³ΠΈΡΠ΅ΡΠΊΠΎΠΌ ΡΡΡΠ΅ΠΊΡΠ΅ ΡΠ΅Π»Π°Π½ΠΊΠ° ΠΈ ΠΌΠΎΡΡΠΈΠ½Π° Π² ΠΎΡΠ»Π°Π±Π»Π΅Π½ΠΈΠΈ ΠΎΡΡΡΠΎΠΉ ΡΠΎΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ Π±ΠΎΠ»ΠΈ
ΠΠΈΠΏΠ΅ΠΏΡΠΈΠ΄Π½ΡΠΉ Π°Π½Π°Π»ΠΎΠ³ Ρ ΠΎΠ»Π΅ΡΠΈΡΡΠΎΠΊΠΈΠ½ΠΈΠ½Π°-4, ΠΎΡΠ»Π°Π±Π»ΡΠ΅Ρ ΡΡΠ΅Π²ΠΎΠΆΠ½ΡΡ ΡΠ΅Π°ΠΊΡΠΈΡ Ρ Β«Π²ΡΡΠΎΠΊΠΎΡΠΌΠΎΡΠΈΠΎΠ½Π°Π»ΡΠ½ΡΡ Β» ΠΌΡΡΠ΅ΠΉ BALB/Ρ ΠΈ ΠΏΡΠΈ ΠΌΠΎΠ΄Π΅Π»ΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ Π°Π»ΠΊΠΎΠ³ΠΎΠ»ΡΠ½ΠΎΠΉ Π°Π±ΡΡΠΈΠ½Π΅Π½ΡΠΈΠΈ Ρ ΠΊΡΡΡ: ΡΡΠ°Π²Π½Π΅Π½ΠΈΠ΅ Ρ ΡΠ΅Π½Π°Π·Π΅ΠΏΠ°ΠΌΠΎΠΌ
Anxiolytic effects of dipeptide endogenous cholecystokinin tetrapeptide analogue GB-115 at the dose range 0,25-2,0 mg/ kg after oral administration were studied in rodents with high emotionality. In βelevated plus-mazeβ test GB-115 anxiolytic activity comparable with phenazepam was shown in inbred βanxiousβ BALB/c mice and βagedβ rats with long-term 10% ethanol experience during ethanol withdrawal. GB-115 at the doses 0,5-2,0 mg/kg didnβt induce sedation, in contrast phenazepam significantly suppressed spontaneous locomotor activity in BALB/c mice in Optovarimex. The data obtained show potent anxiolytic properties GB-115 (tablet 0,001) lacking benzodiazepineβs side-effects in animal models with high emotionality.ΠΠ·ΡΡΠ΅Π½Ρ Π°Π½ΠΊΡΠΈΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠ²ΠΎΠΉΡΡΠ²Π° ΠΠ-115, Π΄ΠΈΠΏΠ΅ΠΏΡΠΈΠ΄Π½ΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΎΠ³Π° ΡΠ½Π΄ΠΎΠ³Π΅Π½Π½ΠΎΠ³ΠΎ ΡΠ΅ΡΡΠ°ΠΏΠ΅ΠΏΡΠΈΠ΄Π° Ρ
ΠΎΠ»Π΅ΡΠΈΡΡΠΎΠΊΠΈΠ½ΠΈΠ½Π° Ρ ΠΆΠΈΠ²ΠΎΡΠ½ΡΡ
Ρ ΠΏΠΎΠ²ΡΡΠ΅Π½Π½ΡΠΌ ΡΡΠΎΠ²Π½Π΅ΠΌ ΡΠΌΠΎΡΠΈΠΎΠ½Π°Π»ΡΠ½ΠΎΡΡΠΈ ΠΏΡΠΈ ΠΏΠ΅ΡΠΎΡΠ°Π»ΡΠ½ΠΎΠΌ Π²Π²Π΅Π΄Π΅Π½ΠΈΠΈ Π² Π΄ΠΈΠ°ΠΏΠ°Π·ΠΎΠ½Π΅ Π΄ΠΎΠ· 0,25-2,0 ΠΌΠ³/ΠΊΠ³. Π ΡΠ΅ΡΡΠ΅ ΠΠΠ Π°Π½ΠΊΡΠΈΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠ΅ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ ΠΠ-115, ΡΠΎΠΏΠΎΡΡΠ°Π²ΠΈΠΌΠΎΠ΅ Ρ ΡΠ΅Π½Π°Π·Π΅ΠΏΠ°ΠΌΠΎΠΌ, ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ Ρ ΠΈΠ½Π±ΡΠ΅Π΄Π½ΡΡ
ΠΌΡΡΠ΅ΠΉ BALB/c ΠΈ Ρ Β«ΡΡΠ°ΡΡΡ
Β» ΠΊΡΡΡ, ΠΏΠΎΡΡΠ΅Π±Π»ΡΠ²ΡΠΈΡ
10% ΡΠ°ΡΡΠ²ΠΎΡ ΡΡΠ°Π½ΠΎΠ»Π° Π² ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ 33 Π½Π΅Π΄Π΅Π»Ρ Π½Π° ΡΠΎΠ½Π΅ Π°Π»ΠΊΠΎΠ³ΠΎΠ»ΡΠ½ΠΎΠΉ Π΄Π΅ΠΏΡΠΈΠ²Π°ΡΠΈΠΈ. ΠΠ-115 Π² Π΄ΠΎΠ·Π°Ρ
0,5-2,0 ΠΌΠ³/ΠΊΠ³ Π½Π΅ Π²ΡΠ·ΡΠ²Π°Π» ΡΠ΅Π΄Π°ΡΠΈΠ²Π½ΠΎΠ³ΠΎ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ, Π² ΡΠΎ Π²ΡΠ΅ΠΌΡ ΠΊΠ°ΠΊ ΡΠ΅Π½Π°Π·Π΅ΠΏΠ°ΠΌ ΡΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈ Π·Π½Π°ΡΠΈΠΌΠΎ ΡΠ³Π½Π΅ΡΠ°Π» ΡΠΏΠΎΠ½ΡΠ°Π½Π½ΡΡ Π΄Π²ΠΈΠ³Π°ΡΠ΅Π»ΡΠ½ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΌΡΡΠ΅ΠΉ BALB/c Π² Π°ΠΊΡΠΎΠΌΠ΅ΡΡΠ΅. ΠΠΎΠ»ΡΡΠ΅Π½Π½ΡΠ΅ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ Π΄Π΅ΠΌΠΎΠ½ΡΡΡΠΈΡΡΡΡ Π½Π°Π»ΠΈΡΠΈΠ΅ Ρ ΠΠ-115 (ΡΠ°Π±Π»Π΅ΡΠΊΠ° 0,001) Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΡΡ
Π°Π½ΠΊΡΠΈΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ²ΠΎΠΉΡΡΠ², Π»ΠΈΡΡΠ½Π½ΡΡ
ΠΏΠΎΠ±ΠΎΡΠ½ΡΡ
ΡΡΡΠ΅ΠΊΡΠΎΠ², Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠ½ΡΡ
Π΄Π»Ρ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΡΡ
Π±Π΅Π½Π·ΠΎΠ΄ΠΈΠ°Π·Π΅ΠΏΠΈΠ½Π°, Π½Π° ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΡΡ
ΠΌΠΎΠ΄Π΅Π»ΡΡ
Ρ ΠΏΠΎΠ²ΡΡΠ΅Π½Π½ΡΠΌ ΡΡΠΎΠ²Π½Π΅ΠΌ ΡΡΠ΅Π²ΠΎΠΆΠ½ΠΎΡΡ
ΠΡΠ΅Π½ΠΊΠ° ΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠΉ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ Π½ΠΎΠ²ΠΎΠ³ΠΎ Π΄ΠΈΠΏΠ΅ΠΏΡΠΈΠ΄Π½ΠΎΠ³ΠΎ ΠΌΠΈΠΌΠ΅ΡΠΈΠΊΠ° 2-ΠΉ ΠΏΠ΅ΡΠ»ΠΈ BDNF ΠΏΡΠΈ ΡΠΎΠ²ΠΌΠ΅ΡΡΠ½ΠΎΠΌ Π²Π²Π΅Π΄Π΅Π½ΠΈΠΈ Ρ ΡΡΠ°Π½ΠΎΠ»ΠΎΠΌ
To assess the pharmacological safety of the dipeptide mimetic of the 2nd loop of BDNF (compound GTS-201) when co-administered with ethanol, its effect on the alteration in motor activity induced by ethanol during acute and subchronic administration in mice C57Bl/6 and DBA/2 was studied. It was found that GTS-201 at a dose of 5.0 mg / kg, i.p., without affecting spontaneous motor activity per se, after a preliminary acute administration prevented the development of a sedative reaction caused by ethanol (2.0 g/ kg, i.p.) in C57Bl/6 mice. After subchronic administration, GTS-201 is devoid of psychostimulant effect and impact on the formation of ethanol-induced behavioral sensitization in DBA/2 mice. The data obtained indicate the absence of a psychostimulant component and synergism in the pharmacological profile of GTS-201 when used with ethanol at low dose.ΠΠ»Ρ ΠΎΡΠ΅Π½ΠΊΠΈ ΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠΉ Π±Π΅Π·ΠΎΠΏΠ°ΡΠ½ΠΎΡΡΠΈ Π΄ΠΈΠΏΠ΅ΠΏΡΠΈΠ΄Π½ΠΎΠ³ΠΎ ΠΌΠΈΠΌΠ΅ΡΠΈΠΊΠ° 2-ΠΉ ΠΏΠ΅ΡΠ»ΠΈ BDNF (ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠ΅ ΠΠ’Π‘-201) ΠΏΡΠΈ ΡΠΎΠ²ΠΌΠ΅ΡΡΠ½ΠΎΠΌ Π²Π²Π΅Π΄Π΅Π½ΠΈΠΈ Ρ ΡΡΠ°Π½ΠΎΠ»ΠΎΠΌ ΠΈΠ·ΡΡΠ΅Π½ΠΎ Π΅Π³ΠΎ Π²Π»ΠΈΡΠ½ΠΈΠ΅ Π½Π° ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ Π΄Π²ΠΈΠ³Π°ΡΠ΅Π»ΡΠ½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ, Π²ΡΠ·ΡΠ²Π°Π΅ΠΌΠΎΠ΅ ΡΡΠ°Π½ΠΎΠ»ΠΎΠΌ ΠΏΡΠΈ ΠΎΡΡΡΠΎΠΌ ΠΈ ΡΡΠ±Ρ
ΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΌ Π²Π²Π΅Π΄Π΅Π½ΠΈΠΈ Ρ ΠΌΡΡΠ΅ΠΉ C57Bl/6 ΠΈ DBA/2. Π£ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ ΠΠ’Π‘-201 Π² Π΄ΠΎΠ·Π΅ 5,0 ΠΌΠ³/ΠΊΠ³, Π²/Π±, Π½Π΅ Π²Π»ΠΈΡΡ Π½Π° ΡΠΏΠΎΠ½ΡΠ°Π½Π½ΡΡ Π΄Π²ΠΈΠ³Π°ΡΠ΅Π»ΡΠ½ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ per se, ΠΏΡΠΈ ΠΏΡΠ΅Π΄Π²Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎΠΌ ΠΎΠ΄Π½ΠΎΠΊΡΠ°ΡΠ½ΠΎΠΌ Π²Π²Π΅Π΄Π΅Π½ΠΈΠΈ ΠΏΡΠ΅ΠΏΡΡΡΡΠ²ΠΎΠ²Π°Π» ΡΠ°Π·Π²ΠΈΡΠΈΡ ΡΠ΅Π΄Π°ΡΠΈΠ²Π½ΠΎΠΉ ΡΠ΅Π°ΠΊΡΠΈΠΈ, Π²ΡΠ·ΡΠ²Π°Π΅ΠΌΠΎΠΉ ΡΡΠ°Π½ΠΎΠ»ΠΎΠΌ (2,0 Π³/ΠΊΠ³, Π²/Π±) Ρ ΠΌΡΡΠ΅ΠΉ C57Bl/6. ΠΡΠΈ ΡΡΠ±Ρ
ΡΠΎΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΌ Π²Π²Π΅Π΄Π΅Π½ΠΈΠΈ ΠΠ’Π‘-201 Π»ΠΈΡΡΠ½ ΠΏΡΠΈΡ
ΠΎΡΡΠΈΠΌΡΠ»ΠΈΡΡΡΡΠ΅Π³ΠΎ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ ΠΈ Π²Π»ΠΈΡΠ½ΠΈΡ Π½Π° ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΏΠΎΠ²Π΅Π΄Π΅Π½ΡΠ΅ΡΠΊΠΎΠΉ ΡΠ΅Π½ΡΠΈΠ±ΠΈΠ»ΠΈΠ·Π°ΡΠΈΠΈ, ΠΈΠ½Π΄ΡΡΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ ΡΡΠ°Π½ΠΎΠ»ΠΎΠΌ, Ρ ΠΌΡΡΠ΅ΠΉ DBA/2. ΠΠΎΠ»ΡΡΠ΅Π½Π½ΡΠ΅ Π΄Π°Π½Π½ΡΠ΅ ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΡΡ ΠΎΠ± ΠΎΡΡΡΡΡΡΠ²ΠΈΠΈ Π² ΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠΌ ΠΏΡΠΎΡΠΈΠ»Π΅ ΠΠ’Π‘-201 ΠΏΡΠΈΡ
ΠΎΡΡΠΈΠΌΡΠ»ΠΈΡΡΡΡΠ΅Π³ΠΎ ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΠ° ΠΈ ΡΠΈΠ½Π΅ΡΠ³ΠΈΠ·ΠΌΠ° ΠΏΡΠΈ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠΈ Ρ ΡΡΠ°Π½ΠΎΠ»ΠΎΠΌ Π² Π½ΠΈΠ·ΠΊΠΎΠΉ Π΄ΠΎΠ·Π΅
Π‘ΡΠ°Π²Π½ΠΈΡΠ΅Π»ΡΠ½ΠΎΠ΅ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ ΠΊΠ°ΡΠ΄ΠΈΠΎΠΏΡΠΎΡΠ΅ΠΊΡΠΎΡΠ½ΠΎΠ³ΠΎ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ ΡΡΠΈΠΌΠ΅ΡΠ°Π·ΠΈΠ΄ΠΈΠ½Π° ΠΈ ΡΠ°Π±ΠΎΠΌΠΎΡΠΈΠ·ΠΎΠ»Π° Π³ΠΈΠ΄ΡΠΎΡ Π»ΠΎΡΠΈΠ΄Π° Ρ ΠΊΡΡΡ ΡΠΎ ΡΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π²ΡΠ΅ΠΉΡΡ Π°Π»ΠΊΠΎΠ³ΠΎΠ»ΡΠ½ΠΎΠΉ ΠΊΠ°ΡΠ΄ΠΈΠΎΠΌΠΈΠΎΠΏΠ°ΡΠΈΠ΅ΠΉ Π² ΡΡΠ»ΠΎΠ²ΠΈΡΡ ΠΏΡΠΎΠ΄ΠΎΠ»ΠΆΠ°ΡΡΠ΅Π³ΠΎΡΡ ΠΏΠΎΡΡΠ΅Π±Π»Π΅Π½ΠΈΡ ΡΡΠ°Π½ΠΎΠ»Π°
In the previousLy deveLoped transLation modeL of aLcohoLic cardiomyopathy in white nonLinear rats was studied the cardioprotective effects of trimetazidine and fabomotizoLe hydrochLoride that were injected daiLy during the 25th - 28th weeks of continued consumption of 10% ethanoL It is shown that trimetazidine (30 mg/kg/day i.p.) and fabomotizoLe hydrochLoride (15 mg/kg / day i.p/) in the above conditions, significantLy reduced the remodeLing of the Left and right ventricLes of the heart and increased the heart contractiLe function.ΠΠ° ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°Π½Π½ΠΎΠΉ ΡΠ°Π½Π΅Π΅ ΡΡΠ°Π½ΡΠ»ΡΡΠΈΠΎΠ½Π½ΠΎΠΉ ΠΌΠΎΠ΄Π΅Π»ΠΈ Π°Π»ΠΊΠΎΠ³ΠΎΠ»ΡΠ½ΠΎΠΉ ΠΊΠ°ΡΠ΄ΠΈΠΌΠΈΠΎΠΏΠ°ΡΠΈΠΈ Ρ Π±Π΅Π»ΡΡ
Π±Π΅ΡΠΏΠΎΡΠΎΠ΄Π½ΡΡ
ΠΊΡΡΡ ΠΈΠ·ΡΡΠ°Π»ΠΈ ΠΊΠ°ΡΠ΄ΠΈΠΎΠΏΡΠΎΡΠ΅ΠΊΡΠΎΡΠ½ΡΠ΅ ΡΡΡΠ΅ΠΊΡΡ ΡΡΠΈΠΌΠ΅ΡΠ°Π·ΠΈΠ΄ΠΈΠ½Π° ΠΈ ΡΠ°Π±ΠΎΠΌΠΎΡΠΈΠ·ΠΎΠ»Π° Π³ΠΈΠ΄ΡΠΎΡ
Π»ΠΎΡΠΈΠ΄Π°, Π²Π²ΠΎΠ΄ΠΈΠΌΡΡ
Π΅ΠΆΠ΅Π΄Π½Π΅Π²Π½ΠΎ Π² ΠΏΠ΅ΡΠΈΠΎΠ΄ 25-28-ΠΉ Π½Π΅Π΄Π΅Π»Ρ ΠΏΡΠΎΠ΄ΠΎΠ»ΠΆΠ°ΡΡΠ΅Π³ΠΎΡΡ ΠΏΠΎΡΡΠ΅Π±Π»Π΅Π½ΠΈΡ 10% ΡΡΠΈΠ»ΠΎΠ²ΠΎΠ³ΠΎ ΡΠΏΠΈΡΡΠ°. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ ΡΡΠΈΠΌΠ΅ΡΠ°Π·ΠΈΠ΄ΠΈΠ½ (30 ΠΌΠ³/ΠΊΠ³/ΡΡΡ, Π²/Π±) ΠΈ ΡΠ°Π±ΠΎΠΌΠΎΡΠΈΠ·ΠΎΠ»Π° Π³ΠΈΠ΄ΡΠΎΡ
Π»ΠΎΡΠΈΠ΄ (15 ΠΌΠ³/ΠΊΠ³/ΡΡΡ, Π²/Π±) Π² ΡΠΊΠ°Π·Π°Π½Π½ΡΡ
Π²ΡΡΠ΅ ΡΡΠ»ΠΎΠ²ΠΈΡΡ
ΡΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈ Π·Π½Π°ΡΠΈΠΌΠΎ ΡΠΌΠ΅Π½ΡΡΠ°Π»ΠΈ ΡΠ΅ΠΌΠΎΠ΄Π΅Π»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π»Π΅Π²ΠΎΠ³ΠΎ ΠΈ ΠΏΡΠ°Π²ΠΎΠ³ΠΎ ΠΆΠ΅Π»ΡΠ΄ΠΎΡΠΊΠΎΠ² ΡΠ΅ΡΠ΄ΡΠ° ΠΈ ΡΠ²Π΅Π»ΠΈΡΠΈΠ²Π°Π»ΠΈ ΡΠΎΠΊΡΠ°ΡΠΈΡΠ΅Π»ΡΠ½ΡΡ ΡΡΠ½ΠΊΡΠΈΡ ΡΠ΅ΡΠ΄ΡΠ°