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New painkillers could thwart opioids‘ fatal flaw
Nov 16, 2017 … When people die from overdoses of opioids, whether prescription pain medications or street drugs, it is the suppression of breathing that almost always kills them. The drugs act on neuronal receptors to dull pain, but those in the brain stem also control breathing. When activated, they can signal respiration …
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SCIENCESHOTS
Tropical fish fiend for opioids, too
Aug 25, 2017 … After just 5 days, the trained fish were visiting the opioid-delivering platform almost 2000 times every 50 minutes, the team reports online today in Behavioral Brain Research . When no drug was present, they visited the platform only about 200 times. Fish normally avoid shallow water, where they’re more …
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Forecasting the opioid epidemic | Science
Nov 4, 2016 … Summary. Since 2000, almost half a million Americans have died from drug overdoses. This modern plague—largely driven by opioid addiction—degrades health, saps productivity, spawns crime, and devastates families, all at enormous societal cost. How did we get here, and what do we do now?
DOI: 10.1126/science.aal2943
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SCIENCEINSIDER
Expert panel to FDA: time to hold opioids to a new standard …
Jul 13, 2017 … To help bolster its campaign against an epidemic of opioid abuse that now kills about 90 people a day, the U.S. Food and Drug Administration (FDA) last year called for help from an independent advisory panel. The resulting report, released today by the National Academies of Sciences, Engineering, and …
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Plasma membrane localization of the μ-opioid receptor controls …
Spatiotemporal opioid receptor signaling. The μ-opioid receptor (MOR) is a GPCR that mediates the effects of endogenous opioids and opioid analgesics, such as morphine. Different MOR agonists produce different biological effects, in part by differentially regulating receptor phosphorylation and internalization. In cells …
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LATEST NEWS
Could pot help solve the U.S. opioid epidemic?
Nov 3, 2016 … Hints are emerging that cannabis could be an alternative to opioid painkillers.
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SCIENCEINSIDER
Can social media help prevent opioid abuse?
Jul 13, 2016 … Can a social media strategy that has helped gay men combat HIV now help curb the abuse of powerful opioid drugs? That’s the question a team of researchers at the University of California, Los Angeles (UCLA), is asking in a pilot study highlighted by White House officials last week. The Harnessing Online …
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Modeling the growth of opioid overdose deaths | Sciencehound
Jun 5, 2017 … In his recent editorial Forecasting the opioid epidemic, Don Burke discussed the rise in opioid addiction in the United States and pointed to the need for data.
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LATEST NEWS
Why painkillers sometimes make the pain worse
Nov 3, 2016 … Mark Hutchinson could read the anguish on the participants’ faces in seconds. As a graduate student at the University of Adelaide in Australia in the late 1990s, he helped with studies in which people taking methadone to treat opioid addiction tested their pain tolerance by dunking a forearm in ice water.
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Quantitative Encoding of the Effect of a Partial Agonist on Individual …
Here, we addressed this question by focusing on morphine, a partial agonist drug for μ-type opioid peptide receptors (MORs), and by combining quantitative mass spectrometry with cell biological analysis to investigate the reduced efficacy of morphine, compared to that of a peptide full agonist, in promoting receptor …
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Biased agonists of the kappa opioid receptor suppress pain and itch …
Nov 29, 2016 … Itch relief from biased agonists. Activating the kappa opioid receptor (KOR) can relieve itching that is not caused by allergic reactions. However, compounds that activate this receptor also cause unwanted side effects, such as dysphoria and sedation. KOR activation can trigger multiple downstream …
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REPORT
Complete biosynthesis of opioids in yeast | Science
Toward opioids without poppy fields. Producing opioids without having to depend on field-grown poppies would be of great benefit. Synthetic production could potentially produce more-effective drugs with fewer side effects. Now, Galanie et al. have engineered yeast to produce the opioid compounds thebaine and …
DOI: 10.1126/science.aac9373
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REPORT
Placebo and Opioid Analgesia– Imaging a Shared Neuronal Network
It has been suggested that placebo analgesia involves both higher order cognitive networks and endogenous opioid systems. The rostral anterior cingulate cortex (rACC) and the brainstem are implicated in opioidanalgesia, suggesting a similar role for these structures in placebo analgesia. Using positron emission …
DOI: 10.1126/science.1067176
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LATEST NEWS
Why taking morphine, oxycodone can sometimes make pain worse …
May 30, 2016 … There’s an unfortunate irony for people who rely on morphine, oxycodone, and other opioid painkillers: The drug that’s supposed to offer you relief can actually make you more sensitive to pain over time. That effect, known as hyperalgesia, could render these medications gradually less effective for chronic …
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RESEARCH ARTICLE
Alcohol Consumption Induces Endogenous Opioid Release in the …
Jan 11, 2012 … Studies in animals suggest that release of endogenous opioids by ethanol promotes further consumption. To examine this issue in humans and to determine where in the brain endogenous opioids act to promote alcohol consumption, we measured displacement of a radiolabeled μ opioid receptor agonist, …
DOI: 10.1126/scitranslmed.3002902
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Hope For Nonaddictive Opioid Painkillers | In the Pipeline
Mar 13, 2017 … No one needs to be told about the opioid painkiller problem in this country. There are legal, commerical, regulatory, and ethical ways to look at it, but from a pharmacological standpoint, the whole thing would be a lot easier to deal with if there were any highly effective non-addictive painkillers. But that’s …
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EDITORS’ CHOICE
Calcium Channels Brought Inside by Opioid-Like Receptor | Science …
Nociceptin is an endogenous pain-alleviating peptide that binds to the receptor ORL1, which is structurally similar to opioid receptors. ORL1 was recently found to interact directly with N-type calcium channels, resulting in tonic, agonist-independent inhibition. Altier et al. extend these observations and report that extended …
DOI: 10.1126/stke.3162006tw460
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Synergistic regulation of serotonin and opioid signaling contributes …
Jan 10, 2017 … The balance of pronociceptive (pain-promoting) serotonin signaling mediated by the 5-HT4 receptor and antinociceptive (pain-relieving) opioid signaling mediated by the mu opioid receptor (MOR) was altered. Mice lacking Nav1.7 had much more efficient signaling by the opioid arm, shifting the balance …
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ARTICLES
Opioid peptides endorphins in pituitary and brain | Science
Opioid peptides endorphins in pituitary and brain. See allHide authors and affiliations. Science 17 Sep 1976: Vol. 193, Issue 4258, pp. 1081-1086. DOI: 10.1126/science.959823. A Goldstein. Find this author on Google Scholar · Find this author on PubMed · Search for this author on this site · Article; Info & Metrics; eLetters …
DOI: 10.1126/science.959823
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REPORT
Induction of Synaptic Long-Term Potentiation After Opioid Withdrawal
Abstract. μ-Opioid receptor (MOR) agonists represent the gold standard for the treatment of severe pain but may paradoxically also enhance pain sensitivity, that is, lead to opioid-induced hyperalgesia (OIH). We show that abrupt withdrawal from MOR agonists induces long-term potentiation (LTP) at the first synapse in pain …
DOI: 10.1126/science.1171759
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Broad-Spectrum, Non-Opioid Analgesic Activity by Selective …
Development of analgesic agents for the treatment of severe pain requires the identification of compounds that are devoid of opioid receptor liabilities. A potent (inhibition constant = 37 picomolar) neuronal nicotinic acetylcholine receptor (nAChR) ligand called ABT-594 was developed that has antinociceptive properties …
DOI: 10.1126/science.279.5347.77
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REPORT
Regional Mu Opioid Receptor Regulation of Sensory and Affective …
The endogenous opioid system is involved in stress responses, in the regulation of the experience of pain, and in the action of analgesic opiate drugs. We examined the function of the opioid system and μ-opioidreceptors in the brains of healthy human subjects undergoing sustained pain. Sustained pain induced the …
DOI: 10.1126/science.1060952
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Increased Abundance of Opioid Receptor Heteromers After Chronic …
Abstract. The μ and δ types of opioid receptors form heteromers that exhibit pharmacological and functional properties distinct from those of homomeric receptors. To characterize these complexes in the brain, we generated antibodies that selectively recognize the μ-δ heteromer and blocked its in vitro signaling. With these …
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ASSOCIATION AFFAIRS
S&T Policy Forum examines evolving opioid epidemic | Science
Apr 28, 2017 … Summary. More young people are using heroin, and powerful drug additives are causing more overdoses. Science: 356 (6336). Science. Vol 356, Issue 6336 28 April 2017. Table of Contents · Print Table of Contents · Advertising (PDF) · Classified (PDF) · Masthead (PDF). Article Tools. Email. Thank you for …
DOI: 10.1126/science.356.6336.390-a
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Constitutive μ-Opioid Receptor Activity Leads to Long-Term …
The properties and functions of µ-opioid receptors have been studied intensively with respect to the binding of endogenous or exogenous ligands. However, much less is known about the constitutive, ligand-independent, activation of opioid receptors. Working in mice, Corder et al. (p. 1394) observed the prolonged …
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EDITORS’ CHOICE
Paradoxical Pain After Opioid Withdrawal | Science Signaling
Opioids are widely used by both pain patients and substance abusers. Withdrawal from opioids can be complicated by opioid-induced hyperalgesia, a paradoxical amplification of pain by opioids. Drdla et al. detected a novel cellular opioid action that may help to explain this paradoxical pain: the induction of synaptic …
DOI: 10.1126/scisignal.279ec240
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EDITORS’ CHOICE
A Painful Endogenous Opioid | Science Signaling
Dynorphin A1-17 is derived from proteolytic processing of prodynorphin and has high affinity for μ, δ, and κ opioid receptors. However, increased amounts of dynorphin A are found in models of chronic pain, and antibodies against dynorphin A alleviate, rather than potentiate, pain. Lai et al. show that a fragment of dynorphin …
DOI: 10.1126/stke.3642006tw407
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Podcast: The impact of legal pot on opioid abuse, and a very early …
Nov 3, 2016 … This week, news writer Greg Miller chats with us about how the legalization of marijuana in certain U.S. states is having an impact on the nation’s opioid problem. Plus, Sarah Crespi talks to Sascha Drewlo about a new method for profiling the DNA of fetuses very early on in pregnancy. [Image: …
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LATEST NEWS
Is a new class of painkillers on the horizon?
Feb 27, 2017 … Scientists are chasing a new lead on a class of drugs that may one day fight both pain and opioid addiction. It’s still early days, but researchers report that they’ve discovered a new small molecule that binds selectively to a long-targeted enzyme, halting its role in pain and addiction while not interfering with …
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Synthesizing the Opioid Peptides
Synthesizing the Opioid Peptides. The opioid peptides are synthesized as parts of large precursor molecules that may be split to yield different products in different cells. The biosynthesis of the opioid pep- tides illustrates what seemsto be a gen- eral trend in neurobiology. Likemany other peptides that act in the nervous.
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