Mu opioid receptor-dependent and independent
components in effects of tramadol
by
Ide S, Minami M, Ishihara K, Uhl GR, Sora I, Ikeda K.
Division of Psychobiology, Tokyo Institute of Psychiatry,
2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan;
Laboratory of Neuropharmacology,
Faculty of Pharmaceutical Sciences,
Hiroshima International University,
Kure 737-0112, Japan.
Neuropharmacology. 2006 Sep;51(3):651-8.

ABSTRACT

Tramadol is thought to induce analgesia via both opioid and non-opioid pathways, although the precise mechanisms remain to be elucidated. In this study, we investigated the roles of the mu-opioid receptor (MOP) in analgesic and rewarding effects of tramadol by using MOP knockout (KO) mice. Tramadol-induced antinociception, assessed by hot-plate and tail-flick tests, was significantly reduced in heterozygous and homozygous MOP-KO mice when compared with that in wild-type mice. Interestingly, however, tramadol retained its ability to induce significant antinociception in homozygous MOP-KO mice. The tramadol-induced antinociception remaining in homozygous MOP-KO mice was not significantly affected by methysergide, a serotonin receptor antagonist, but was partially blocked by yohimbine, an adrenaline alpha2 receptor antagonist, and both naloxone, a non-selective opioid receptor antagonist, and yohimbine. In addition, antinociceptive effects of an active tramadol metabolite M1 were abolished or remarkably reduced in MOP-KO mice. On the other hand, neither wild-type nor homozygous MOP-KO mice showed significant place preference for tramadol in a conditioned place preference test, although there were slight tendencies toward preference in wild-type mice and avoidance in homozygous MOP-KO mice. These results strongly support the idea suggested in the previous pharmacological studies that MOP and the adrenaline alpha2 receptor mediate most of the analgesic properties of tramadol.

Rats like tramadol
Tramadol plus pindolol
Tramadol and analgesia
Tramadol: pharmacology
Tramadol as an antidepressant
Tramadol: risk/benefit analysis
Tramadol versus buprenorphine
Tramadol : morning or evening?
Methadone for tramadol addicts?
Tramadol, morphine and the stomach
Tramadol, noradrenaline and dopamine
Pharmacokinetics and pharmacodynamics
Tramadol, depression and Parkinson's disease

Refs
and further reading

HOME
HedWeb
Nootropics
cocaine.wiki
Future Opioids
BLTC Research
MDMA/Ecstasy
Superhapiness?
Utopian Surgery?
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World

The Good Drug Guide
The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family