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Synthesis and Investigation of Mixed μ-Opioid and δ-Opioid Agonists as Possible Bivalent Ligands for Treatment of Pain
2017, Journal of Heterocyclic ChemistryA new potent analgesic agent with reduced liability to produce morphine tolerance
2015, Brain Research BulletinEndogenous opioid function mediates the association between laboratory-evoked pain sensitivity and morphine analgesic responses
2013, PainCitation Excerpt :Animal studies suggest that EO function does influence opioid analgesic responses, although direction of these effects appears inconsistent. Although several animal studies indicate possible cross-tolerance between EOs and opioid analgesic medications [22,36,48], others suggest synergistic effects, with direct application of EOs (e.g., β-endorphin) or manipulations that trigger release of EOs (e.g., forced swim, tail suspension, exercise) enhancing responsiveness to opioid analgesics [2,5,12,13,17,31,46,47,49,50]. Human positron emission tomography imaging findings are indirectly supportive as well, indicating that a placebo manipulation with EO enhancing effects [20] increases opioid analgesic responses [4].
Antinociceptive effects of two deltorphins analogs in the tail-immersion test in rats
2013, PeptidesCitation Excerpt :Porreca et al. [33] provided evidence that the DOR agonists, such as DADLE and DPDPE at the dose that did not produce significant analgesia when given alone, significantly potentiated morphine response in mice when co-administered i.c.v. with morphine. Similar potentiation of morphine analgesia was observed after co-administration a synthetic enkephalin analog, FK33824 and morphine, both compounds at the doses that given alone in mice exhibited little or no analgesic activity [25]. In our study in rats, DEL-6 was co-injected with morphine, and both compounds were delivered at non-analgesic doses.
Spinal interaction between the highly selective μ agonist DAMGO and several δ opioid receptor ligands in naive and morphine-tolerant mice
2013, Brain Research BulletinCitation Excerpt :In acute pain models significant tolerance develops to morphine within three days by systemic administration (He and Lee, 1998; Kornetsky and Bain, 1968; Riba et al., 2002; Willimas et al., 1969). One of the hypotheses might be the tolerance development by local interactions of the opioid receptors in the spinal cord (Larson et al., 1980; Vaught and Takemori, 1979) This phenomenon has been studied since 1979 and significant amount of data indicate the cooperation between μ and δ opioid receptors (Lee et al., 1980; Rothman and Westfall, 1983). The physical interaction – the formation of μδ heterodimers – was proven in 2000 (George et al., 2000).
Functional relevance of μ-δ opioid receptor heteromerization: A Role in novel signaling and implications for the treatment of addiction disorders: From a symposium on new concepts in mu-opioid pharmacology
2012, Drug and Alcohol DependenceCitation Excerpt :Consequently, this review will attempt to summarize what is presently known about the μ–δ heteromer, in addition to the latest emerging ideas implicating the μ–δ heteromer as a novel target for the treatment of chronic pain and addiction disorders. Pharmacological tools provided some of the earliest evidence supporting the existence of heteromers of the μ and δ receptors, when it was observed that endogenous δ-selective ligands, such as Leu-enkephalin, and exogenous synthetic analogues of Leu-enkephalin (FK33824) had the ability to synergistically enhance low levels of morphine-mediated analgesia in a dose dependent manner in vivo (Lee et al., 1980). Subsequent to these initial findings, additional research observed that pretreatment with the selective δ-antagonist naltrindole prior to acute- or multiple administrations of morphine sulfate resulted in a robust attenuation of tolerance to morphine (Abdelhamid et al., 1991).