PPL-103

PPL-103 is an investigational, mixed opioid receptor partial agonist being developed by Phoenix PharmaLabs as a potent, non‑addictive analgesic and potential therapy for opioid and cocaine addiction. It is a morphinan derivative (α-methyl-cyclopropylmethyl-morphinan) with high binding affinity at mu, kappa and delta opioid receptors and a balanced partial agonist profile characterized by low efficacy at the mu receptor and greater but still partial efficacy at kappa and delta receptors, which enables strong antinociception at roughly one‑tenth the morphine dose in animal models while markedly reducing euphoria, dysphoria, respiratory depression, physical dependence and constipation.[1][7][9][2][4] In preclinical studies, PPL-103 has not been self‑administered by rats, does not induce significant conditioned place preference or aversion, prevents withdrawal and relapse behaviors, and reduces cocaine self‑administration and reinstatement in rodent models of cocaine use disorder, supporting its dual development for acute pain and substance use disorders.[7][4][2][10][3] The compound is protected by a composition‑of‑matter patent and has been advanced with support from US Department of Defense and NIH/NIDA grants toward first‑in‑human studies as a “poly‑receptor” non‑addictive opioid for acute pain, with the company positioning it for future out‑licensing after early phase clinical proof of concept.[2][1][5][12][13]

Other names

α-methyl-cyclopropylmethyl-morphinan