A new potent analgesic agent with reduced liability to produce morphine tolerance.

A new potent analgesic agent with reduced liability to produce morphine tolerance. Brain Res Bull. 2015 Jul 30; Authors: Kiraly K, Caputi FF, Hanuska A, Kató E, Balogh M, Köles L, Palmisano M, Riba P, Hosztafi S, Romualdi P, Candeletti S, Ferdinandy P, Fürst S, Al-Khrasani M Abstract The therapeutic use of opioids is limited by the development of tolerance to the analgesic effect and the cellular and molecular mechanisms underlying this phenomenon are still not completely understood. For this reason the search for new analgesic derivatives, endowed with lower tolerance, is always an active field. The newly synthesized 14- O -Methylmorphine-6-sulfate (14- O -MeM6SU) shows high efficacy in in vitro assays and a strong analgesic action in the rat tail flick test. The aim of present work was to investigate: the analgesic effect of 14- O -MeM6SU in mouse tail-flick test; the tolerance to analgesic effect of 14- O -MeM6SU compared to morphine in mice, the effects of test compounds on glutamatergic neurotransmission by measuring spontaneous excitatory postsynaptic currents (sEPSCs) of layer V pyramidal cells from rat prefrontal cortices; and the effect of acute and chronic 14- O -MeM6SU treatments on opioid receptor gene expression in SH-SY5Y neuroblastoma cells expressing μ-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors. 14- O -MeM6SU was 16 times more potent than morphine in analgesia and had long duration of actio...
Source: Brain Research Bulletin - Category: Neurology Authors: Tags: Brain Res Bull Source Type: research