Biasing μ Opioid Receptors with G Protein Inhibitors to Improve Opioid Analgesics

Opioid Analgesics

Intensive research on the neurobiology of pain over the past two decades has revealed many receptors, ion channels and enzymes with potential as novel targets for development of a new generation of analgesic agents. However, despite large investment in preclinical and clinical development of small molecules and biologics as potential novel pain therapeutics, very few have reached the clinic. He...

Opioid and Nonopioid Analgesics

Pharmacological Profiles of Oligomerized μ-Opioid Receptors

Opioids are widely prescribed pain relievers with multiple side effects and potential complications. They produce analgesia via G-protein-protein coupled receptors: μ-, δ-, κ-opioid and opioid receptor-like 1 receptors. Bivalent ligands targeted to the oligomerized opioid receptors might be the key to developing analgesics without undesired side effects and obtaining effective treatment for opi...

Chronic treatment with the opioid antagonist naltrexone favours the coupling of spinal cord μ-opioid receptors to Gαz protein subunits.

Sustained administration of opioid antagonists to rodents results in an enhanced antinociceptive response to agonists. We investigated the changes in spinal μ-opioid receptor signalling underlying this phenomenon. Rats received naltrexone (120 μg/h; 7 days) via osmotic minipumps. The antinociceptive response to the μ-agonist sufentanil was tested 24 h after naltrexone withdrawal. In spinal cord...

Non-opioid analgesics

C describe the concept of multimodal analgesia and give examples Abstract Opium is the natural substance to which modern narcotics owe their existence. First discovered in the 1500s, opium was the most potent analgesic compound in use, held in high regard, hence its Latin name laudanum (to praise). Subsequent studies into the effects of opium led to the discovery of the opioid receptors, and th...