Open-chain Opioids

Diphenylpropylamines: the opioid pharmacophore assembled on a flexible open chain rather than a rigid fused ring system. That is the structural point of the family — methadone, levomethadone, dextromoramide, dipipanone, piritramide and dextropropoxyphene look nothing like morphine and reach the same receptor.

What varies most here is time. Methadone's half-life is long and differs widely between individuals, so it accumulates over the first days of any new regime and a comfortable first dose says little about the third; that lag, rather than the peak, is what kills during induction. Methadone also prolongs the QT interval and antagonises NMDA receptors, so it is not simply a slow morphine. Dextropropoxyphene's metabolite is cardiotoxic in a way naloxone does not address, which is why the drug was withdrawn in many countries. Full μ agonists throughout, with respiratory depression additive with every depressant.