Experimental assessment of ladasten and GB-115 effects on the antinociceptive tolerance to morphine
Abstract
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.
Keywords
ладастен,
ГБ-115,
толерантность к морфину,
анальгезия,
крысы,
ladasten,
GB-115,
tolerance to morphine,
antinociception,
rats
About the Authors
M. A. Konstantinopolsky
FSBI «Zakusov Institute of Pharmacology»
Russian Federation
Russian Federation
I. V. Chernyakova
FSBI «Zakusov Institute of Pharmacology»
Russian Federation
Russian Federation
L. G. Kolik
FSBI «Zakusov Institute of Pharmacology»
Russian Federation
Russian Federation
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Review
For citations:
Konstantinopolsky M.A., Chernyakova I.V., Kolik L.G. Experimental assessment of ladasten and GB-115 effects on the antinociceptive tolerance to morphine. Pharmacokinetics and Pharmacodynamics. 2016;(2):40-45. (In Russ.)
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