Systematic evaluation of whether in vitro methods can predict in vivo opioid analgesic efficacy, safety and tolerability (2006-2009)

Clinically available strong opioid analgesics such as morphine, produce many undesirable side-effects including respiratory depression and constipation. The aim of this is project is to use a more contemporary drug discovery approach that considers opioid receptor complexes as legitimate novel targets, in order to successfully identify novel opioid analgesics that have a higher margin of safety and tolerability than morphine. Specifically, we will use a panel of in vitro screening assays in conjunction with a targeted library of putative opioid ligands to identify novel opioids that produce potent pain relief with a markedly reduced propensity for producing respiratory depression and/or constipation compared with morphine.