Buprenorphine: An Analgesic with an Expanding Role in the Treatment of Opioid Addiction

Abstract

Buprenorphine, a long-acting opioid with both agonist and antagonist properties, binds to ì-opioid (OP 3 ), ê-opioid (OP 2 ), ä-opioid (OP 1 ), and nociceptin (ORL-1) receptors. Its actions at these receptors have not been completely characterized, although buprenorphine is generally regarded as a ì-opioid receptor partial agonist and a ê-opioid receptor antagonist. Its pharmacology is further complicated by an active metabolite, norbuprenorphine. Although buprenorphine can be used as an analgesic agent, it is of greater importance in the treatment of opioid abuse. Because of its partial agonist activity at ì-opioid receptors and its long half-life, buprenorphine has proven to be an excellent alternative to methadone for either maintenance therapy or detoxification of the opioid addict. Although buprenorphine may ultimately prove to be superior to methadone in the maintenance of the pregnant addict, its effects on the developing fetus must be carefully evaluated.

The mu opioid receptor is involved in buprenorphine-induced locomotor stimulation and conditioned place preference

“…However, the central question remains to be asked is that what makes buprenorphine different from morphine then? One probable explanation is that buprenorphine acts as a high affinity partial agonist at the MOP (Cowan et al, 1977a,b;Lutfy et al, 2003;Martin et al, 1976; for review see Cowan, 2003;Lutfy and Cowan, 2004;Robinson, 2002;Tzschentke, 2002). The other possibility could be the slow dissociation rate of buprenorphine from the MOP (for reviews see Cowan, 2003;Lutfy and Cowan, 2004;Robinson, 2002;Tzschentke, 2002).…”

“…Repeated intermittent opioid administration leads to the development of locomotor sensitization, a response that is thought to play an important role in the development and maintenance of drug dependency (for reviews see Robinson andBerridge, 1993, 2000). Wildtype mice treated with buprenorphine once daily for 5 days and challenged with buprenorphine on day 11 exhibited locomotor sensitization.…”

“…The increase in accumbal dopamine is also important for the motor stimulatory action of morphine (Hnasko et al, 2005). The motor stimulatory action of morphine and other drugs of abuse is enhanced following their repeated intermittent administration, a phenomenon referred to as locomotor sensitization which is thought to play an important role in the development and maintenance of drug dependency, particularly craving (for review see Robinson andBerridge, 1993, 2000).…”

“…Although buprenorphine is described as a partial agonist at the MOP (Martin et al, 1976; for reviews see Cowan, 2003;Lutfy and Cowan, 2004;Ohlsen and Pilowsky, 2005;Robinson, 2002;Tzschentke, 2002), its mechanism of action is not fully understood For example, there is evidence showing its interaction with the kappa and delta opioid receptors as well as with the opioid receptor-like (ORL-1) receptor (Bloms-Funke et al, 2000;Hawkinson et al, 2000;Huang et al, 2001;Lutfy et al, 2003;Negus et al, 1989Negus et al, , 2002Sadee et al, 1982;Wnendt et al, 1999; for review see Lutfy and Cowan, 2004). Thus, buprenorphine represents an opioid with unique and complex pharmacology because it can simultaneously act as an agonist and/or antagonist at different classes of opioid receptors.…”

Behavioural outcomes of four-year-old children prenatally exposed to methadone or buprenorphine: a test of three risk models

“…Prenatal exposure to opioids such as methadone and buprenorphine causes neonatal abstinence syndrome (NAS) in approximately half of all prenatally-exposed infants (Jones et al, 2010). While both methadone and buprenorphine act by binding to opioid receptors in the central nervous system, methadone is a full mu-opioid agonist while buprenorphine is only a partial mu-opioid agonist (Robinson, 2002). Buprenorphine has been associated with less severe NAS from that observed with methadone; this may be due to lower placental transfer of buprenorphine compared to methadone (Nanovskaya, Deshmukh, Brooks, & Ahmed, 2002).…”