The Sound of Evolution
Propoxyphene
Mechanism of action:
Propoxyphene is an opioid and a diphenylpropylamine derivative. Propoxyphene has weak agonist activity at the mu-opioid receptor. Through coupling to Gi/o proteins, it inhibits adenylyl cyclase, lowers cAMP, inhibits presynaptic voltage-gated Ca2+ channels, blocks calcium influx, and reduces the release of pain-related neurotransmitters such as glutamate and substance P. At the same time, it activates postsynaptic K+ channels, promotes potassium efflux, and causes neuronal hyperpolarization. Propoxyphene also has significant cardiac electrophysiological toxicity, as it blocks cardiac sodium channels and leads to QRS prolongation and QT prolongation.
Reference(s):
1. Coda BA et al. (2003). Pharmacokinetics and bioavailability of single-dose intranasal hydromorphone hydrochloride in healthy volunteers. Anesth Analg.
2. Ulens C et al. (1999). Norpropoxyphene-induced cardiotoxicity is associated with changes in ion-selectivity and gating of HERG currents. Cardiovasc Res.
3. Tyers MB et al. (1980). A classification of opiate receptors that mediate antinociception in animals. Br J Pharmacol.