Buprenorphine &amp;ndash; an attractive opioid with underutilized potential in treatment of chronic pain

Khanna, Ish; Pillarisetti, Sivaram

doi:10.2147/jpr.s85951

Cited by 83 publications

(46 citation statements)

References 75 publications

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“…Therefore, production of cAMP (the endpoint of adenylyl cyclase regulation) is an amplified response relative to G-protein activation. In any case, if similar to reports for mu-OR partial agonists such as buprenorphine [39], the partial agonist activity of M6S at mu- and/or delta-ORs may provide several distinct advantages to treatment of chronic pain when compared to opioids exhibiting full agonism.…”

Section: Discussionsupporting

confidence: 66%

Antinociceptive effects of the 6- O -sulfate ester of morphine in normal and diabetic rats: Comparative role of mu- and delta-opioid receptors

Yadlapalli

Ford

Ketkar

et al. 2016

Pharmacological Research

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This study determined the antinociceptive effects of morphine and morphine-6-O-sulphate (M6S) in both normal and diabetic rats, and evaluated the comparative role of mu-opioid receptors (mu-ORs) and delta-opioid receptors (delta-ORs) in the antinociceptive action of these opioids. In vitro characterization of mu-OR and delta-OR-mediated signaling by M6S and morphine in stably transfected Chinese hamster ovary (CHO-K1) cells showed that M6S exhibited a 6-fold higher affinity for delta-ORs and modulated G-protein and adenylyl cyclase activity via delta-ORs more potently than morphine. Interestingly, while morphine acted as a full agonist at delta-ORs in both functional assays examined, M6S exhibited either partial or full agonist activity for modulation of G-protein or adenylyl cyclase activity, respectively. Molecular docking studies indicated that M6S but not morphine binds equally well at the ligand binding site of both mu- and delta-ORs. In vivo analgesic effects of M6S and morphine in both normal and streptozotocin-induced diabetic Sprague-Dawley rats utilizing the hot water tail flick latency test showed that M6S produced more potent antinociception than morphine in both normal rats and diabetic rats. This difference in potency was abrogated following antagonism of delta- but not mu- or kappa (kappa-ORs) opioid receptors. During 9 days of chronic treatment, tolerance developed to morphine-treated but not to M6S-treated rats. Rats that developed tolerance to morphine still remained responsive to M6S. Collectively, this study demonstrates that M6S is a potent and efficacious mu/delta opioid analgesic with a delayed tolerance profile when compared to morphine in both normal and diabetic rats. Perspective This study demonstrates that M6S acts at both mu- and delta-ORs, and adds to the growing evidence that the use of mixed mu/delta opioid agonists in pain treatment may have clinical benefit.

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Section: Discussionsupporting

confidence: 66%

Antinociceptive effects of the 6- O -sulfate ester of morphine in normal and diabetic rats: Comparative role of mu- and delta-opioid receptors

Yadlapalli

Ford

Ketkar

et al. 2016

Pharmacological Research

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“…In an effort to combat these adverse effects, the μ-opioid receptor antagonist methylnaltrexone might be used pre-emptively 163 . Alternatively, buprenorphine, a μ-opioid receptor partial agonist and a κ-opioid receptor and δ-opioid receptor antagonist, might offer analgesia with less frequent and less severe adverse gastrointestinal effects 164 . Finally, non-narcotic analgesics such as GABA analogues, serotonin–noradrenaline reuptake inhibitors and tri-cyclic anti depressants might have a role as adjuncts for neuropathic gastrointestinal pain 162 .…”

Section: Managementmentioning

confidence: 99%

Acute graft-versus-host disease of the gut: considerations for the gastroenterologist

Naymagon

Wong

et al. 2017

Nat Rev Gastroenterol Hepatol

118

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Haematopoietic stem cell transplantation (HSCT) is central to the management of many haematological disorders. A frequent complication of HSCT is acute graft-versus-host disease (GVHD), a condition in which immune cells from the donor attack healthy recipient tissues. The gastrointestinal system is among the most common sites affected by acute GVHD, and severe manifestations of acute GVHD of the gut portends a poor prognosis in patients after HSCT. Acute GVHD of the gastrointestinal tract presents both diagnostic and therapeutic challenges. Although the clinical manifestations are nonspecific and overlap with those of infection and drug toxicity, diagnosis is ultimately based on clinical criteria. As reliable serum biomarkers have not yet been validated outside of clinical trials, endoscopic and histopathological evaluation continue to be utilized in diagnosis. Once a diagnosis of gastrointestinal acute GVHD is established, therapy with systemic corticosteroids is typically initiated, and non-responders can be treated with a wide range of second-line therapies. In addition to treating the underlying disease, the management of complications including profuse diarrhoea, severe malnutrition and gastrointestinal bleeding is paramount. In this Review, we discuss strategies for the diagnosis and management of acute GVHD of the gastrointestinal tract as they pertain to the practising gastroenterologist.

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“…The T max is 2.5–3.0 hours with steady-state concentrations reached prior to the sixth dose, and it has a half-life of 27.6 hours 47. The half-life for sublingual and transdermal buprenorphine formulations ranges from 20 hours to 73 hours 48. The mean plasma elimination half-life of BBUP is 27.6±11.2 hours 49.…”

Section: Pharmacokineticsmentioning

confidence: 99%

Management of moderate to severe chronic low back pain with buprenorphine buccal film using novel bioerodible mucoadhesive technology

Pergolizzi¹,

Raffa²,

Fleischer³

et al. 2016

JPR

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With a global prevalence of ~9%–12%, low back pain (LBP) is a serious public health issue, associated with high costs for treatment and lost productivity. Chronic LBP (cLBP) involves central sensitization, a neuropathic pain component, and may induce maladaptive coping strategies and depression. Treating cLBP is challenging, and current treatment options are not fully satisfactory. A new BioErodible MucoAdhesive (BEMA®) delivery system for buprenorphine has been developed to treat cLBP. The buccal buprenorphine (BBUP) film developed for this product (Belbuca™) allows for rapid delivery and titration over a greater range of doses than was previously available with transdermal buprenorphine systems. In clinical studies, BBUP was shown to effectively reduce pain associated with cLBP at 12 weeks with good tolerability. The most frequently reported side effects with the use of BBUP were nausea, constipation, and vomiting. There was no significant effect on the QT interval vs placebo. Chronic pain patients using other opioids can be successfully rotated to BBUP without risk of withdrawal symptoms or inadequate analgesia. The role of BBUP in managing cLBP remains to be determined, but it appears to be a promising new product in the analgesic arsenal in general.

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Buprenorphine – an attractive opioid with underutilized potential in treatment of chronic pain

Cited by 83 publications

References 75 publications

Antinociceptive effects of the 6- O -sulfate ester of morphine in normal and diabetic rats: Comparative role of mu- and delta-opioid receptors

Antinociceptive effects of the 6- O -sulfate ester of morphine in normal and diabetic rats: Comparative role of mu- and delta-opioid receptors

Acute graft-versus-host disease of the gut: considerations for the gastroenterologist

Management of moderate to severe chronic low back pain with buprenorphine buccal film using novel bioerodible mucoadhesive technology

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