Peptidic delta opioid receptor agonists produce antidepressant-like effects in the forced swim test and regulate BDNF mRNA expression in rats

Torregrossa, Mary M.; Jutkiewicz, Emily M.; Mosberg, Henry I.; Balboni, Gianfranco; Watson, Stanley J.; Woods, James H.

doi:10.1016/j.brainres.2005.11.005

Cited by 87 publications

(66 citation statements)

References 31 publications

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“…After repeated administration, antidepressants evoke changes in neurotrophic factor expression and provoke associated neurogenesis (Nibuya et al, 1995;Dranovsky and Hen, 2006). Although there is somewhat mixed evidence whether ␦-opioid receptor agonists may be enhancing monoaminergic transmission, there is evidence that ␦-opioid receptor agonists will evoke increases in brain-derived neurotrophic factor, indicating that there may be some overlap with standard antidepressants' actions (Torregrossa et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Preclinical Pharmacology of AZD2327: A Highly Selective Agonist of the δ-Opioid Receptor

Hudzik

Maciag²,

Smith³

et al. 2011

J Pharmacol Exp Ther

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In the present article, we summarize the preclinical pharmacology of 4-{(R)-(3-aminophenyl)[4-(4-fluorobenzyl)-piperazin-1-yl]methyl}-N,N-diethylbenzamide (AZD2327), a highly potent and selective agonist of the ␦-opioid receptor. AZD2327 binds with sub-nanomolar affinity to the human opioid receptor (K i ϭ 0.49 and 0.75 nM at the C27 and F27 isoforms, respectively) and is highly selective (Ͼ1000-fold) over the human -and -opioid receptor subtypes as well as Ͼ130 other receptors and channels. In functional assays, AZD2327 shows full agonism at human ␦-opioid receptors ([ 35 S]GTP␥ EC 50 ϭ 24 and 9.2 nM at C27 and F27 isoforms, respectively) and also at the rat and mouse ␦-opioid receptors. AZD2327 is active in a wide range of models predictive of anxiolytic activity, including a modified Geller-Seifter conflict test and social interaction test, as well as in antidepressant models, including learned helplessness. In animals implanted with microdialysis probes and then given an acute stressor by pairing electric shock delivery with a flashing light, there is an increase in norepinephrine release into the prefrontal cortex associated with this acute anxiety state. Both the benzodiazepine anxiolytic standard diazepam and AZD2327 blocked this norepinephrine release equally well, and there was no evidence of tolerance to these effects of AZD2327. Overall, these data support the role of the ␦-opioid receptor in the regulation of mood, and data suggest that AZD2327 may possess unique antidepressant and anxiolytic activities that could make a novel contribution to the pharmacotherapy of psychiatric disorders.

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Section: Discussionmentioning

confidence: 99%

Preclinical Pharmacology of AZD2327: A Highly Selective Agonist of the δ-Opioid Receptor

Hudzik

Maciag²,

Smith³

et al. 2011

J Pharmacol Exp Ther

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“…97 The list includes more than a dozen agonists, from a variety of chemical structural classes. 69,[98][99][100][101][102][103][104][105][106][107][108][109][110][111][112][113][114][115] Interestingly, at least one study suggests that the antidepressant activity of the tricyclic antidepressant imipramine might be mediated by DOR. 116 Concomitantly, it has been suggested that the effects of tricyclic antidepressants on neuropathic pain require DOR stimulation, at least in mice.…”

Section: Other Therapeutic Potentialmentioning

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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“…A variety of manipulations increase BDNF production in brain but most of these (e.g., seizures, chronic treatment with antidepressants or cannabinoids) (Isackson et al, 1991;Castren, 2003;Butovsky et al, 2005;Torregrossa et al, 2005) would not be suitable for treating age-related losses of synaptic plasticity. BDNF levels are also higher in rats and mice with elevated levels of voluntary exercise (wheel running) relative to non-running, age-matched controls (Cotman and Berchtold, 2002;Farmer et al, 2004) but it is not clear that this provides a route for increasing the neurotrophin in subjects living in normal environments where locomotor activity is commonplace.…”

Section: Modulatorsmentioning

confidence: 99%

Synaptic plasticity in early aging

Lynch

Rex

Gall

2006

Ageing Research Reviews

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Studies of how aging affects brain plasticity have largely focused on old animals. However, deterioration of memory begins well in advance of old age in animals, including humans; the present review is concerned with the possibility that changes in synaptic plasticity, as found in the long-term potentiation (LTP) effect, are responsible for this. Recent results indicate that impairments to LTP are in fact present by early middle age in rats but only in certain dendritic domains. The search for the origins of these early aging effects necessarily involves ongoing analyses of how LTP is induced, expressed, and stabilized. Such work points to the conclusion that cellular mechanisms responsible for LTP are redundant and modulated both positively and negatively by factors released during induction of potentiation. Tests for causes of the localized failure of LTP during early aging suggest that the problem lies in excessive activity of a negative modulator. The view of LTP as having redundant and modulated substrates also suggests a number of approaches for reversing age-related losses. Particular attention will be given to the idea that induction of brain-derived neurotrophic factor, an extremely potent positive modulator, can be used to provide long periods of normal plasticity with very brief pharmacological interventions. The review concludes with a consideration of how the selective, regional deficits in LTP found in early middle age might be related to the global phenomenon of brain aging. #

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Peptidic delta opioid receptor agonists produce antidepressant-like effects in the forced swim test and regulate BDNF mRNA expression in rats

Cited by 87 publications

References 31 publications

Preclinical Pharmacology of AZD2327: A Highly Selective Agonist of the δ-Opioid Receptor

Preclinical Pharmacology of AZD2327: A Highly Selective Agonist of the δ-Opioid Receptor

Delta opioid agonists: a concise update on potential therapeutic applications

Synaptic plasticity in early aging

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