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

• Main Authors: M. A. Konstantinopolsky (Author), I. V. Chernyakova (Author), L. G. Kolik (Author)
• Format: Book
• Published: LLC "Publisher OKI", 2016-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2587-7836; 2686-8830
• Keywords: ладастен; гб-115; толерантность к морфину; анальгезия; крысы; ladasten; gb-115; tolerance to morphine; antinociception; rats; Pharmacy and materia medica; RS1-441
• Source: Фармакокинетика и Фармакодинамика, Vol 0, Iss 2, Pp 40-45 (2016)

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.