Buprenorphine: Demonstration of physical dependence liability

Dum, Jane; Bläsig, J; Herz, A.

doi:10.1016/0014-2999(81)90163-1

Cited by 58 publications

(38 citation statements)

References 9 publications

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“…This was evidenced by the decline in antinociceptive effect of buprenorphine after 39 h (Figure 1) and the total absence of antinociception at 72 h despite continued intake of buprenorphine. Dum et al (1981) made a similar observation, reporting that rats treated twice daily for four days with buprenorphine (0.5 mg/kg s.c.) lost the antinociceptive effect by the fifth day. As antinociception was assessed only on the fifth day (Dum et al 1981), there is no way of knowing if tolerance appeared earlier.…”

Section: Discussionmentioning

confidence: 62%

The antinociceptive efficacy of buprenorphine administered through the drinking water of rats

2007

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SummaryPostoperative pain management in laboratory animals is important for animal welfare and required under law in many countries. Frequent injection of analgesics to rodents after surgery is stressful for the animals and labour-intensive for animal care personnel. An alternative dosing scheme such as administration of analgesics in the drinking water would be desirable. However, the efficacy of a chronic oral analgesic treatment via this route has not yet been documented. This study investigated the antinociceptive efficacy of buprenorphine administered ad libitum via the drinking water of laboratory rats. The antinociceptive efficacy of buprenorphine in drinking water was compared with repeated subcutaneous injections. A comparison was also made between buprenorphine in drinking water and the combination of one single subcutaneous injection of buprenorphine followed by buprenorphine in drinking water. Antinociception was assessed by use of an analgesiometric model measuring the rats' latency time to withdrawal from a noxious heat stimulus applied to the plantar surface of the paw. Results revealed that buprenorphine in drinking water (0.056 mg/mL) induced significant increases in paw withdrawal latency times during a three-day period of administration with a maximal effect at 39 h after the start of buprenorphine administration. One single injection of buprenorphine (0.1 mg/kg s.c.) followed by buprenorphine in the drinking water (0.056 mg/mL) induced an earlier onset of antinociception than buprenorphine in drinking water alone. In contrast, buprenorphine (0.1 mg/kg s.c.) injected every 8 h over a period of three days did not result in significant increases in paw withdrawal latency times. In conclusion, our results suggest that one single subcutaneous injection of buprenorphine followed by buprenorphine in drinking water may be a viable treatment option for the relief of pain in laboratory rats, but at the doses used in this study in pain-free rats it was associated with a decrease in water intake and some behavioural changes.

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Section: Discussionmentioning

confidence: 62%

The antinociceptive efficacy of buprenorphine administered through the drinking water of rats

2007

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“…Despite the fact that buprenorphine is a potent analgesic, at higher doses the antinociceptive effect of the drug sometimes reaches a plateau without producing a maximal response, i.e., it produces a submaximal antinociceptive effect [12,18,51]. Partial agonism at the mu opioid receptor is thought to be the underlying mechanism for this action of buprenorphine [27,46].…”

Section: The Role Of Orl-1 Receptors In the Antinociceptive Effect Ofmentioning

confidence: 99%

“…Buprenorphine produces not only a submaximal antinociceptive effect [12,18,51], but also attenuates the action of morphine and other full agonists. In some cases, buprenorphine totally abolishes the action of full agonists [12,45].…”

Section: The Role Of Orl-1 Receptors In the Ability Of Buprenorphine mentioning

confidence: 99%

“…The underlying mechanism for this antagonism remains elusive. Previous studies have used the term "partial agonism" at mu opioid receptors [12,18] or antagonism at the kappa opioid receptor [45] to describe the antagonistic action of buprenorphine. Since intracerebroventricular OFQ/N administration blocks the antinociceptive effect of morphine and other opioid analgesics [for review, see 65], we hypothesized that buprenorphine also inhibits the action of morphine via activation of the ORL-1 receptor.…”

Section: The Role Of Orl-1 Receptors In the Ability Of Buprenorphine mentioning

confidence: 99%

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Buprenorphine: A Unique Drug with Complex Pharmacology

Lutfy

Cowan²

2004

281

232

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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.

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“…The results should help clarify the nature of the biochemical mechanism responsible for the decline in the agonist action of buprenorphine at high doses. Dum, Blasig & Herz, 1981). To test the withdrawal-precipitating potency of buprenorphine, experiments were also performed in animals made highly tolerantdependent on morphine.…”

Section: Introductionmentioning

confidence: 99%

In vivo RECEPTOR BINDING OF THE OPIATE PARTIAL AGONIST, BUPRENORPHINE, CORRELATED WITH ITS AGONISTIC AND ANTAGONISTIC ACTIONS

Dum

Herz

1981

British J Pharmacology

Self Cite

161

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1 In order to gain more insight into the mechanisms behind the actions of opiate partial agonists, an analysis of the dual agonist/antagonist properties of the partial agonist, buprenorphine, was made in conjunction with in vivo binding studies of the drug in the rat. 2 Buprenorphine revealed a bell-shaped dose-response curve for antinociception peaking at approx. 0.5 mg/kg subcutaneously. It antagonized morphine antinociception at doses which normally have agonistic effects and produced maximum antagonistic effects at doses above those having prominent agonistic activity. The withdrawal precipitating potency of buprenorphine as measured in highly morphine-dependent rats was present at doses above those having agonistic activity. The entire dose-response curve for buprenorphine was shifted symmetrically to the right by the opiate antagonist, naltrexone. 3 The dose-dependent occupation of receptors in vivo by buprenorphine seemed to be almost complete over the agonist dosage range; almost no further receptor occupation over the antagonist range was seen.4 The possibility is discussed that site-to-site receptor interactions leading to cooperativity of effect may be the best explanation of these results.

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Buprenorphine: Demonstration of physical dependence liability

Cited by 58 publications

References 9 publications

The antinociceptive efficacy of buprenorphine administered through the drinking water of rats

The antinociceptive efficacy of buprenorphine administered through the drinking water of rats

Buprenorphine: A Unique Drug with Complex Pharmacology

In vivo RECEPTOR BINDING OF THE OPIATE PARTIAL AGONIST, BUPRENORPHINE, CORRELATED WITH ITS AGONISTIC AND ANTAGONISTIC ACTIONS

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