Experimental assessment of ladasten and GB-115 effects on the antinociceptive tolerance to morphine

The development of morphine-induced antinociceptive tolerance limits its therapeutic efficacy in pain management. Effects of non-benzodiazepine anxiolytics ladasten and GB-115 on the development of antinociceptive tolerance to morphine were studied in albino male rats. The tolerance was induced by d...

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Main Authors: M. A. Konstantinopolsky, I. V. Chernyakova, L. G. Kolik
Format: Article
Language:Russian
Published: LLC “Publisher OKI” 2016-03-01
Series:Фармакокинетика и Фармакодинамика
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Online Access:https://www.pharmacokinetica.ru/jour/article/view/173
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author M. A. Konstantinopolsky
I. V. Chernyakova
L. G. Kolik
author_facet M. A. Konstantinopolsky
I. V. Chernyakova
L. G. Kolik
author_sort M. A. Konstantinopolsky
collection DOAJ
description The development of morphine-induced antinociceptive tolerance limits its therapeutic efficacy in pain management. Effects of non-benzodiazepine anxiolytics ladasten and GB-115 on the development of antinociceptive tolerance to morphine were studied in albino male rats. The tolerance was induced by daily sub-chronic administration of morphine (2,0 mg/kg, i.p., twice daily for 5 days) and assessed in immersion tail-flick test on days 1 and 5. Concomitant sub-chronic administration of dipeptide anxiolytic GB-115 (0,1 mg/kg/5 days, i.p.), developed on the base of endogenous tetrapeptide cholecystokinin (CCK), followed by morphine (2,0 mg/kg), reversed the antinociceptive tolerance to morphine on day 5. GB-115 per se at the same anxiolytic dose demonstrated a short-term analgesic activity on days 1 and 5. In contrast, 2-aminoadamantane derivative Ladasten (50,0 mg/kg/5 days, i.p.) with psychostimulant and anxiolytic activity, failed to do so. Ladasten at dose employed in the study, did not exert any effects on pain threshold on days 1 and 5. Our results suggest that in this well-characterized model of acute somatic pain, the development of tolerance to the antinociceptive effect of systemic morphine can be prevented by co-administration with GB-115.
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2686-8830
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series Фармакокинетика и Фармакодинамика
spelling doaj-art-cd1ff9a31f954d18ac8b950b42be9c3b2025-08-20T03:42:31ZrusLLC “Publisher OKI”Фармакокинетика и Фармакодинамика2587-78362686-88302016-03-01024045172Experimental assessment of ladasten and GB-115 effects on the antinociceptive tolerance to morphineM. A. Konstantinopolsky0I. V. Chernyakova1L. G. Kolik2FSBI «Zakusov Institute of Pharmacology»FSBI «Zakusov Institute of Pharmacology»FSBI «Zakusov Institute of Pharmacology»The development of morphine-induced antinociceptive tolerance limits its therapeutic efficacy in pain management. Effects of non-benzodiazepine anxiolytics ladasten and GB-115 on the development of antinociceptive tolerance to morphine were studied in albino male rats. The tolerance was induced by daily sub-chronic administration of morphine (2,0 mg/kg, i.p., twice daily for 5 days) and assessed in immersion tail-flick test on days 1 and 5. Concomitant sub-chronic administration of dipeptide anxiolytic GB-115 (0,1 mg/kg/5 days, i.p.), developed on the base of endogenous tetrapeptide cholecystokinin (CCK), followed by morphine (2,0 mg/kg), reversed the antinociceptive tolerance to morphine on day 5. GB-115 per se at the same anxiolytic dose demonstrated a short-term analgesic activity on days 1 and 5. In contrast, 2-aminoadamantane derivative Ladasten (50,0 mg/kg/5 days, i.p.) with psychostimulant and anxiolytic activity, failed to do so. Ladasten at dose employed in the study, did not exert any effects on pain threshold on days 1 and 5. Our results suggest that in this well-characterized model of acute somatic pain, the development of tolerance to the antinociceptive effect of systemic morphine can be prevented by co-administration with GB-115.https://www.pharmacokinetica.ru/jour/article/view/173ладастенгб-115толерантность к морфинуанальгезиякрысыladastengb-115tolerance to morphineantinociceptionrats
spellingShingle M. A. Konstantinopolsky
I. V. Chernyakova
L. G. Kolik
Experimental assessment of ladasten and GB-115 effects on the antinociceptive tolerance to morphine
Фармакокинетика и Фармакодинамика
ладастен
гб-115
толерантность к морфину
анальгезия
крысы
ladasten
gb-115
tolerance to morphine
antinociception
rats
title Experimental assessment of ladasten and GB-115 effects on the antinociceptive tolerance to morphine
title_full Experimental assessment of ladasten and GB-115 effects on the antinociceptive tolerance to morphine
title_fullStr Experimental assessment of ladasten and GB-115 effects on the antinociceptive tolerance to morphine
title_full_unstemmed Experimental assessment of ladasten and GB-115 effects on the antinociceptive tolerance to morphine
title_short Experimental assessment of ladasten and GB-115 effects on the antinociceptive tolerance to morphine
title_sort experimental assessment of ladasten and gb 115 effects on the antinociceptive tolerance to morphine
topic ладастен
гб-115
толерантность к морфину
анальгезия
крысы
ladasten
gb-115
tolerance to morphine
antinociception
rats
url https://www.pharmacokinetica.ru/jour/article/view/173
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AT ivchernyakova experimentalassessmentofladastenandgb115effectsontheantinociceptivetolerancetomorphine
AT lgkolik experimentalassessmentofladastenandgb115effectsontheantinociceptivetolerancetomorphine