Antidepressant‐like effects of BU10119, a novel buprenorphine analogue with mixed κ/μ receptor antagonist properties, in mice

Abstract

This article is part of a themed section on Emerging Areas of Opioid Pharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.14/issuetoc.

Targeting opioid receptor signaling in depression: do we need selective κ opioid receptor antagonists?

“…Clinical evidence is supportive of this hypothesis; Alkermes have combined buprenorphine with the MOP antagonist samidorphan in a single sublingual tablet (ALKS5461) and in a 1:1 combination that provides KOP receptor antagonism and antagonism or extremely low stimulation at MOP receptors. ALKS5461 has been shown to have potential in the treatment of major depressive disorder [72,73] confirming the pre-clinical findings with buprenorphine-naltrexone and BU10119 [58,62].…”

“…The combination dose of buprenorphine/naltrexone (both 1 mg/kg) produced no locomotor effects, was not rewarding nor aversive but did produce antidepressant and anxiolytic like responses in the forced swim and novelty-induced hypophagia tasks [58]. More recently, we have shown that a novel compound, BU10119, derived from buprenorphine, with a pharmacology resembling combination buprenorphine/naltrexone, also shows antidepressant-like responses [62]. BU10119 was also able to block stress-induced analgesia but not stress-induced increases in corticosterone [62].…”

“…BU10119 was also able to block stress-induced analgesia but not stress-induced increases in corticosterone [62]. Others have shown that stress-induced behaviours can be blocked by KOP antagonists, such as norBNI, even though corticosterone levels may or may not have been affected (see discussion in [62]). …”

“…More recently, we have shown that a novel compound, BU10119, derived from buprenorphine, with a pharmacology resembling combination buprenorphine/naltrexone, also shows antidepressant-like responses [62]. BU10119 was also able to block stress-induced analgesia but not stress-induced increases in corticosterone [62]. Others have shown that stress-induced behaviours can be blocked by KOP antagonists, such as norBNI, even though corticosterone levels may or may not have been affected (see discussion in [62]).…”

Coexistence of Chronic Pain and Depression: A Short Review with a Focus on the Antidepressant Effect of Tramadol and Buprenorphine

“…Clinical and pre-clinical studies have demonstrated the efficacy of buprenorphine and its novel analogues in the pharmacotherapy Review Danuta Szkutnik-Fiedler of depression [3,[71][72][73][74][75][76]. Ahmadi et al [73] suggest that a single high-dose of buprenorphine provides a safe, speedy and straightforward means of depression, especially in patients who are opioid dependent.…”