Opioids: a two-faced Janus

Ahlbeck, Karsten

doi:10.1185/03007995.2010.545379

Cited by 58 publications

(43 citation statements)

References 79 publications

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“…1 Unfortunately, opioid-associated adverse effects, such as constipation, nausea, vomiting, somnolence (or mental clouding), urinary retention and pruritus, are relatively common. 2 In addition, the misuse, abuse and diversion of these medications lead to significant individual and societal burdens. 3 Therefore, there is a continuing quest for opioid analgesics that are as efficacious as existing ones, but have less adverse effect or abuse potential.…”

Section: What Is Known and Objectivementioning

confidence: 99%

Delta opioid agonists: a concise update on potential therapeutic applications

Peppin

Raffa

2015

J Clin Pharm Ther

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SUMMARYWhat is known and objective: The endogenous opioid system co-evolved with chemical defences, or at times symbiotic relationships, between plants and other autotrophs and heterotrophic predators -thus, it is not surprising that endogenous opioid ligands and exogenous mimetic ligands produce diverse physiological effects. Among the endogenous opioid peptides (endomorphins, enkephalins, dynorphins and nociception/orphanin FQ) derived from the precursors encoded by four genes (PNOC, PENK, PDYN and POMC) are the pentapeptides Met-enkephalin (Tyr-Gly-Gly-Phe-Met) and Leu-enkephalin (Tyr-Gly-Gly-PheLeu). The physiological effects of the enkephalins are mediated via 7-transmembrane G protein-coupled receptors, including delta opioid receptor (DOR). We present a concise update on the status of progress and opportunities of this approach. Methods: A literature search of the PUBMED database and a combination of keywords including delta opioid receptor, analgesia, mood and individual compounds identified therein, from industry and other source, and from www.clinicaltrials.com. Results and discussion: DOR agonist and antagonist ligands have been developed with ever increasing affinity and selectivity for DOR over other opioid receptor subtypes and studied for therapeutic utility, primarily for pain relief, but also for other clinical endpoints. What is new and conclusion: Selective DOR agonists have been designed with a large increase in therapeutic window for a variety of potential CNS applications including pain, depression, and learning and memory among others. WHAT IS KNOWN AND OBJECTIVE

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Section: What Is Known and Objectivementioning

confidence: 99%

Delta opioid agonists: a concise update on potential therapeutic applications

Peppin

Raffa

2015

J Clin Pharm Ther

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“…However, in addition to pain relief, use of opioids can produce severe adverse effects, such as sedation, respiratory depression, addiction, and alterations in affective state (euphoria or dysphoria, depending upon the opioid used; for reviews, see Benyamin et al, 2008, andAhlbeck, 2011). Because these adverse effects are due to activation of opioid receptors within the central nervous system (CNS), an attractive approach to treat pain, devoid of adverse CNS-mediated effects, is to target inhibitory opioid receptors expressed by peripheral sensory neurons that respond to noxious stimuli (nociceptors) with peripherally restricted opioids.…”

Section: Introductionmentioning

confidence: 99%

Dual Regulation ofδ-Opioid Receptor Function by Arachidonic Acid Metabolites in Rat Peripheral Sensory Neurons

Sullivan

Berg

Clarke

2015

J Pharmacol Exp Ther

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The regulation of opioid receptor system function in peripheral sensory neurons is not well understood. Opioid agonist efficacy to inhibit nociceptor function and to promote antinociception is generally weak under basal conditions and frequently no response occurs. However, in response to a cyclooxygenasedependent metabolite of arachidonic acid (AA) after exposure to inflammatory mediators, such as bradykinin (BK) or exogenous AA, peripheral opioid receptor systems become much more responsive to opioid agonists. In this study, we examined the time course for the induction and maintenance of functional competence of the d-opioid receptor (DOR) system in adult rat nociceptors in culture and in vivo. We found that the responsive state of DOR after pretreatment with BK or exogenous AA is transient (30-60 minutes) and persists for 15-30 minutes after a 15-minute exposure of nociceptors to BK or AA. Interestingly, whereas functional competence of the DOR system could be reinduced with a second application of BK 60 minutes after the first, responsiveness of the DOR system could not be reinduced after an initial exposure to AA. This nonresponsive state of DOR after exogenous AA was mediated by a lipoxygenase (LOX)-dependent metabolite of AA. Intraplantar carrageenan also produced transient DOR functional competence and responsiveness was also reinduced by inhibition of LOX. Thus, the DOR system expressed by peripheral sensory neurons is under dual regulation by cyclooxygenase-and LOX-dependent metabolites of AA.

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“…Following chronic administration of TAP, tolerance development took much longer compared with morphine (Ahlbeck, 2011).…”

Section: Tapentadolmentioning

confidence: 99%

Tramadol Vs Tapentadol: Anew Horizon in Pain Treatment?

Giorgi¹

2012

American Journal of Animal and Veterinary Sciences

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Problem statement: Acute and chronic pain is a common presenting sign in animal species and human beings. Approach: Classical opioids provide very effective pain relief, although they may be less effective in the treatment of chronic pain due to their limited therapeutic windows and the induced opioid receptor down regulation. Atypical opioids, such as tramadol and tapentadol, have a dual mechanism of action and have been designed to overcome these issues through an opiate-sparing effect. Results: Tramadol activates mu opioid receptors and in addition, inhibits serotonin and noradrenalin reuptake. These actions are the result of the different enantiomers and tend to be reliant on their metabolism. Indeed, the O-desmethyltramadol phase I metabolite, is 200-300 times more potent for mu opioid receptor activation than the parental compound. For these reasons, the drug's effectiveness can vary among subjects. In veterinary medicine its effectiveness, especially after oral administration, is still uncertain and controversial. Tapentadol is a novel, atypical opioid with a unique mechanism of action. It was launched on the European drug market at the end of 2011. It has been proposed as the first representative of a new pharmacological class of centrally acting analgesics, namely, the mu opioid receptor agonist, noradrenalin reuptake inhibitors. The first human studies describe this molecule as safe and effective (equianalgesic to morphine). The drug has great potential for veterinary use because it exists as a single enantiomer only, it does not require metabolic activation to be effective and adverse effects triggered by the serotonin reuptake inhibition action are negligible. Conclusion/Recommendations: For these reasons, TAP is a promising compound however at this stage, more investigation is required before it can be recommended for regular use in veterinary medicine, the possibility of undesirable effects is yet to be entirely excluded.

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Opioids: a two-faced Janus

Cited by 58 publications

References 79 publications

Delta opioid agonists: a concise update on potential therapeutic applications

Delta opioid agonists: a concise update on potential therapeutic applications

Dual Regulation ofδ-Opioid Receptor Function by Arachidonic Acid Metabolites in Rat Peripheral Sensory Neurons

Tramadol Vs Tapentadol: Anew Horizon in Pain Treatment?

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