Synergistic combinations of the dual enkephalinase inhibitor PL265 given orally with various analgesic compounds acting on different targets, in a murine model of cancer-induced bone pain

Protecting endogenous enkephalins from their degradation using dual enkephalinase inhibitors (DENKIs) has been shown to elicit antinociceptive responses in various rodent pain models. Antinociceptive effects of the new DENKI PL265 were evaluated in mice inoculated with B16-F10 melanoma cells into the tibia. The oral administration of PL265 (12.5-100 mg/kg) reduced thermal hyperalgesia and mechanical allodynia. […] Read full post »

Modulation of disulfide dual ENKephalinase inhibitors (DENKIs) activity by a transient N-protection for pain alleviation by oral route

The endogenous opioid system, essentially constituted by two opioid receptors which are stimulated by the natural internal effectors enkephalins (Met-enkephalin and Leu-enkephalin), is present at the different sites (peripheral, spinal, central) of the control of pain. We have demonstrated that the protection of the enkephalin inactivation by the two metallopeptidases (neprilysin and neutral amino-peptidase) increases […] Read full post »

Long-lasting oral analgesic effects of N-protected aminophosphinic dual ENKephalinase inhibitors (DENKIs) in peripherally controlled pain

The peripheral endogenous opioid system is critically involved in neuropathic and inflammatory pain generation as suggested by the modulation of opioid receptors expression and enkephalins (ENKs) release observed in these painful conditions. Accordingly, an innovative approach in the treatment of these nocifensive events is to increase and maintain high local concentrations of extracellular pain-evoked ENKs, […] Read full post »

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