Receptor binding, analgesic and antitussive potency of tramadol and other selected opioids.

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Hennies HH, Friderichs E, Schneider J

Receptor binding, analgesic and antitussive potency of tramadol and other selected opioids.

Arzneimittelforschung. 1988 Jul;38(7):877-80.

PubMed ID

2849950 [ View in PubMed

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Abstract

The influence of replacing the phenolic hydroxyl by the methoxy group on opioid receptor binding, analgesic and antitussive action was investigated in the corresponding couples morphine-codeine, hydromorphone-hydrocodone and O-desmethyltramadol (L 235)-tramadol. Binding was studied on rat whole brain membranes (without cerebellum) with the radioligands dihydromorphine (mu-site), ethylketocyclazocine (k-site), D-Ala2-D-Leu5-enkephalin (delta-site) and naloxone (no selective binding). Analgesia (tail flick) and antitussive action (NH3-vapour induced cough) was investigated in rats and ED50 values 10 min after i.v. application were calculated to compare efficacy. All free hydroxyl compounds had higher opioid receptor affinities than the corresponding methoxy derivatives and were more active at the mu-site. The methoxy derivatives codeine and tramadol only had low affinities lacking selectivity towards mu-, kappa-, or delta-binding. Hydrocodone in contrast showed strong and mu-selective binding. The hydroxy compounds had higher analgesic activity than the methoxy congeners and analgesia appeared to correlate with mu-binding affinity. Codeine and hydrocodone were weaker antitussives than the corresponding hydroxy compounds, whereas no significant difference was found between O-desmethyltramadol and tramadol. Only in the tramadol group the methoxy substitution increased antitussive potency in relation to analgesic potency.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Hydrocodone	Mu-type opioid receptor	Protein	Humans	Yes	Agonist	Details
Hydromorphone	Delta-type opioid receptor	Protein	Humans	Yes	Partial agonist	Details