Buprenorphine: Characteristics of binding sites in the rat central nervous system

Villiger, J.W.; Taylor, Kenneth M.

doi:10.1016/0024-3205(81)90529-4

Cited by 67 publications

(42 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Subsequent studies showed that buprenorphine can also bind to kappa and delta opioid receptors (Tables 1 and 2). The existing data show that buprenorphine displays a 10-fold lower affinity for the delta as compared to the mu and kappa opioid receptors (Table 1) [see also, 31,71,83,84,98,99]. Moreover, recent data demonstrate that buprenorphine, at low doses, blocks epsilon receptors as well [62].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Buprenorphine: A Unique Drug with Complex Pharmacology

Lutfy

Cowan²

2004

275

232

View full text Add to dashboard Cite

Buprenorphine, an opioid with mixed agonist-antagonist activity at classical opioid receptors, has been approved recently for the treatment of opioid dependency. Buprenorphine is also used as an analgesic. The buprenorphine dose-response curve is sometimes submaximal, or even bell-shaped, in nociceptive assays, depending upon the nature and intensity of the noxious stimulus. Moreover, buprenorphine, when administered with full agonists, such as morphine, antagonizes the action of these drugs. Partial agonism at the mu opioid receptor and, in some cases, antagonism at the kappa or delta opioid receptor have been considered as possible underlying mechanisms for the ceiling effect and bell-shaped dose-response curve of buprenorphine. While ceiling effects can be explained by partial agonist activity of buprenorphine, the bell-shaped dose-response curve cannot be a consequence of this property of the drug. Recently, buprenorphine has been shown to activate the opioid receptor-like (ORL-1; also known as NOP) receptor. Supraspinal activation of the ORL-1 receptor counteracts the antinociceptive and rewarding actions of morphine, raising the possibility that these actions of buprenorphine can also be altered by its ability to concomitantly activate the ORL-1 receptor. The use of molecular biological techniques has advanced our knowledge regarding the role of opioid receptors in modulation of pain and reward. In particular, generation of opioid receptor knockout mice has proven useful in this regard. Indeed, using knockout mice, we have recently shown that the antinociceptive effect of buprenorphine mediated primarily by the mu opioid receptor is attenuated by the ability of the drug to activate the ORL-1 receptor. Thus, the goal of this review is to provide evidence demonstrating that the ORL-1 receptor plays a functional role not only in the antinociceptive effect of buprenorphine but also in other actions of the drug as well.

show abstract

Section: Introductionmentioning

confidence: 99%

“…Moreover, recent data demonstrate that buprenorphine, at low doses, blocks epsilon receptors as well [62]. Overall, the body of literature suggests that buprenorphine is an opioid with unique and complex pharmacology, i.e., it can act as an agonist and/or antagonist at different classes of opioid receptors [31,71,79,83,84,98,99].…”

Section: Introductionmentioning

confidence: 99%

Buprenorphine: A Unique Drug with Complex Pharmacology

Lutfy

Cowan²

2004

275

232

View full text Add to dashboard Cite

show abstract

“…Unlike many opioid agonists, its use is associated with limited physical dependence and minimal withdrawal symptoms Oasinski et al 1978;Fudala et al 1990). Buprenorphine competes with selec tive ligands for binding to mu, delta, and kappa opioid receptors (Hambrook and Rance 1976; Dum and Herz 1981;Villiger and Taylor 1981;Sadee et al 1982). Preclin ical studies have characterized the in vivo pharmaco logical activity of buprenorphine as that of a partial mu agonist (Martin et al 1976;Cowan et al 1977) and a kappa antagonist (Leander 1988;Negus and Dykstra 1988).…”

mentioning

confidence: 99%

Buprenorphine Reduces Cerebral Glucose Metabolism in Polydrug Abusers

Walsh

Gilson

Jasinski

et al. 1994

Neuropsychopharmacol

View full text Add to dashboard Cite

Buprenorphine is a mixed opioid agonist-antagonist, which acts as a partial mu agonist and a kappa antagonist. The present study evaluated the acute effects of buprenorphine on cerebral glucose metabolism (CMRglc) in six human substance abusers using a double-blind, placebo-controlled, counterbalanced, crossover design. Each subject participated in two positron emission tomographic (PET) studies, 1 week apart, following the injection of buprenorphine (1 mg, intramuscularly) and placebo. Buprenorphine significantly reduced CMRglc and the regional cerebral KEY WORDS: Opioid; Buprenorphine; Glucose metabolism; Drug abuse; Human brain imaging Buprenorphine, a semi-synthetic opioid drug derived from thebaine, is currently marketed in the United States as an analgesic, and is approximately 25 to 50 times as potent as morphine (Cowan et al. 1977). In hu man subjects, it produces effects that are typical of opi oid agonists (Heel et al. 1979). These include analge-

show abstract

“…For pharmacological efficacy, buprenorphine presents 60% to 65% with respect to MOR (partial agonist). [16][17][18][19][20][21][22] These results confirm that the analgesic activity of buprenorphine is mainly mediated by MOR; its partial agonist action reflects the potential existence of a ceiling effect that, in clinical practice, has been estimated to be about 15 to 25 mg daily, 23 a dosage that may not be compatible with the doses usually prescribed in clinical practice.…”

Section: Synthetic Profile Of Buprenorphinementioning

confidence: 74%