Behavioral pharmacology of buprenorphine, with a focus on preclinical models of reward and addiction.
BACKGROUND
Buprenorphine is a potent mu-receptor partial agonist and is widely used as an analgesic drug. It is also increasingly considered to be an alternative to methadone in the maintenance and eventual detoxification of heroin addicts, and also in the treatment of cocaine addiction. So far, buprenorphine has been available as a sublingual tablet and as a solution for IV injection. Recently, a new transdermal formulation of buprenorphine in slow-release matrix patches has been introduced (Transtec) for the treatment of intermediate to severe pain.


OBJECTIVE
The aim of this paper is to review, from a preclinical perspective, the current status of what is known about the behavioral pharmacology of buprenorphine, with a particular emphasis on the issues of reward, addiction, and dependence. It will also point to open questions that should be addressed in the future to improve our understanding of the effects and the mechanisms of action of this drug.


CONCLUSIONS
Since buprenorphine is a potent opioid drug, the issue of addiction and dependence in this context is an important one. Although there are still some gaps in the behavioral pharmacological characterization of buprenorphine, the general conclusion that can be drawn from the reviewed literature is that despite the high affinity of buprenorphine for the mu receptor it appears to be a remarkably safe drug, with a benign overall side effect profile and low addictive and dependence-inducing potential. This favorable side effect profile appears to be due, to a large extent, to the partial agonistic properties of the drug, in combination with its particular receptor kinetics (i.e. very slow dissociation from the mu receptor after binding).
Tzschentke
Thomas M
TM
Grünenthal GmbH, Biomedical Research, Department of Pharmacology, Postfach 500444, 52088 Aachen, Germany. thomas.tzschentke@grunenthal.de
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002047:Buprenorphine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects; D006801:Humans; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone; D012201:Reward; D012646:Self Administration; D019966:Substance-Related Disorders / Q000209:etiology*
D000701:Analgesics, Opioid; D009270:Naloxone; D002047:Buprenorphine