- |||||||||| fentanyl citrate / Generic mfg.
Clinical, PK/PD data, Journal: Population pharmacokinetic model of subcutaneous fentanyl in older acute care patients. (Pubmed Central) - Dec 22, 2021
This is the first report of subcutaneous fentanyl population pharmacokinetic model to evaluate fentanyl pharmacokinetic in older patients. The between subject variability in clearance and subcutaneous absorption rate was relatively high, and some patients recorded high fentanyl concentrations in the context of their titration to effect.
- |||||||||| fentanyl citrate / Generic mfg., methamphetamine / Generic mfg., levamisole / Generic mfg.
Journal: Biosurveillance of Drug Overdoses and Substance Misuse Treated in Selected Emergency Departments in Minnesota, 2017-2020. (Pubmed Central) - Dec 22, 2021
This case study provides an example of how timely opioid overdose data can be effectively used to detect a spike in nonfatal opioid overdoses and inform a strategic, community-level response. ED surveillance for DOSM encounters, enhanced by toxicology testing, can provide local situational awareness on overdoses, prevent potential mischaracterization of the true drug overdose epidemic, and inform harm reduction and drug overdose prevention efforts.
- |||||||||| Instanyl (fentanyl) / Takeda
Clinical, Journal: Evidence-Based Guidelines for Prehospital Pain Management: Recommendations. (Pubmed Central) - Dec 21, 2021
The panel made a strong recommendation for the use of intranasal fentanyl over intravenous (IV) opioids for pediatric patients without intravenous access given the supporting evidence, its effectiveness, ease of administration, and acceptance by patients and providers...The panel made conditional recommendations for the use of either IV ketamine or IV opioids; for either IV NSAIDs or IV opioids; for either IV fentanyl or IV morphine; and for either IV ketamine or IV NSAIDs...Given the lack of a supporting evidence base, the panel was unable to make recommendations for the use of nitrous oxide versus IV opioids, or for IV ketamine in combination with IV opioids versus IV ketamine alone. Taken together, the recommendations emphasize that EMS medical directors and EMS clinicians have a variety of effective options for the management of moderate to severe pain in addition to opioids when designing patient care guidelines and caring for patients suffering from acute pain.
- |||||||||| fentanyl citrate / Generic mfg.
Differences in cognitive behaviors in a Barnes maze assay between female and male rats (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_8086;
Additionally, we intend to more directly investigate the impact of noradrenergic signaling on Barnes maze behavior following opioid administration using the noradrenergic neurotoxin N--N-ethyl-2-bromobenzylamine (DSP-4). Conceptually this will be examined during drug-withdrawal as it is often considered a stressor that leads to relapse behavior in addictions.; Grant Support: VA Merit Award I01-RX-002252-03; NIH R01-DA-042057 (Perrine)
- |||||||||| fentanyl citrate / Generic mfg., naltrexone / Generic mfg., methadone / Generic mfg.
Opioid Biosensors for Pharmacokinetics: Organelles to Whole Animals (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_7546;
Biosensors were directed to the PM, cytoplasm, ER, and Golgi using address sequences. Transfected HeLa cells and transduced primary neurons were imaged under perfusion across a range of [opioid].
- |||||||||| fentanyl citrate / Generic mfg.
Effects of repeated fentanyl treatment on the locomotor activity of adolescent and adult rats (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_7533;
In summary, our results suggest that both adolescent and adult rats showed a progressively enhanced locomotor response after repeated fentanyl exposure. Moreover, adolescent rats were more sensitive to fentanyl after a 10 day, as compared to a two day, abstinence period.; Grant Support: NIH Grant GM083883
- |||||||||| fentanyl citrate / Generic mfg.
Glucagon-like peptide-1 receptor agonist reduces cue- and drug-induced fentanyl seeking in rats (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_7530;
Here, treatment with the GLP-1 receptor agonist, liraglutide (0.3 mg/kg sc), was found to attenuate both cue-induced fentanyl seeking and drug-induced reinstatement of fentanyl seeking at the same efficacy as the currently approved opioid agonist, buprenorphine. Taken together, these data suggest that a known satiety signal, GLP-1, may serve as an effective non-opioid alternative for the treatment of OUD without the risk of opioid dependence or precipitated withdrawal.; Grant Support: NIH Grant DA009813; NIH Grant DA050325
- |||||||||| fentanyl citrate / Generic mfg.
The Effects of Escalated Fentanyl Intake on Decision-Making Dynamics (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_7492;
The results to date suggest that 6-hr fentanyl access had no effect on isomorphic choice; however, 6-hr fentanyl access systematically shifted allomorphic choice, producing increased sensitivity to changes in remifentanil dose during choice. Collectively, the current results suggest that OUD may be the result of relative valuation processes, not necessarily representative of a deficit in decision-making processes generally.; Grant Support: NIDA Grant 5R01DA047368-03
- |||||||||| fentanyl citrate / Generic mfg., methamphetamine / Generic mfg.
Rewarding and relapse effects of levamisole and fentanyl as adulterants in methamphetamine. (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_7447;
Present results suggest that LEV might increase METH effects and play a role in relapse.; Grant Support: Grant from Colombo Plan Secretariat given directly to CINVESTAV.; Scholarship (No. 489884) from Conacyt, Mexico.
- |||||||||| fentanyl citrate / Generic mfg., morphine sulphate / Generic mfg.
Chronic Opioid Administration Potentiates Striatopallidal and Striatonigral GABAergic Transmission (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_7391;
We also discovered that intravenous self-administration (IVSA) of fentanyl enhanced IPSCs from dSPNs to dopamine neurons in the substantia nigra pars compacta (SNc), suppressing dopaminergic activity. Together, these data suggest that chronic opioid use strengthes GABAergic projections from MOR+ dSPNs to both GPh neurons and SNc dopamine neurons, suppressing their activity; such suppression may contribute to the negative emotional states in opioid use disorder.; Grant Support: NIAAA R01AA027768 (J.W.); U01AA025932 (J.W.)
- |||||||||| fentanyl citrate / Generic mfg.
Opioid-induced respiratory depression involves opioid receptors at both central and peripheral sites (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_7264;
Taken together, these data suggest that fentanyl induces activation in nTS neurons. Furthermore, peripheral opioid receptors may play a larger role in driving fentanyl-induced respiratory depression than previously thought.; Grant Support: R33-DA041883; R01-DA041781; T32 DA007261; R01-DA042499
- |||||||||| pregabalin / Generic mfg., gabapentin / Generic mfg.
Discriminative stimulus effects of gabapentin in rats (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_7252;
Similarly, partial substitution observed with fentanyl also suggests some degree of similarity across the subjective effects of these compounds, potentially generated through a shared pharmacological mechanism of action. Overall, the demonstration that gabapentin produces discriminative stimulus effects in rats, which carry a degree of similarity to fentanyl, implies that positive subjective effects may account for increasing trends of gabapentin abuse.
- |||||||||| fentanyl citrate / Generic mfg.
Rescue and prolonged protection from fentanyl overdose with novel bioorthogonal covalent mu opioid receptor antagonists (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_7251;
Moreover, acute administration of TJ-171 to mice 21 minutes after exposure to fentanyl dose-dependently and swiftly reversed MOR agonist-induced respiratory depression and hyperlocomotion, maintaining that protection against additional doses of fentanyl 12 hours later. These results validate the development of selective bio-orthogonal covalent MOR antagonists against fentanyl overdose.
- |||||||||| fentanyl citrate / Generic mfg.
Evaluating Common Behavioral Factors Underlying Chronic Pain and Depression that Contribute to Opioid Abuse (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_7178;
These data show individual markers that may be key indicators of opioid abuse susceptibility. The combination of these behavioral features across painful and depressive-like states could help predict fentanyl consumption by highlighting individual phenotypic differences.; Grant Support: NIH Grant R00DA043572-03
- |||||||||| Byetta (exenatide) / AstraZeneca
Glucagon-like peptide-1 receptor agonism in the interpeduncular nucleus decreases opioid reinstatement (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_7016;
Oxycodone is one of the most commonly abused opioid analgesics, and over one half of all opioid overdose deaths are associated with synthetic opioids including fentanyl and its analogs...Our previous studies showed that systemic administration of the GLP-1R agonist Exendin-4 (Ex-4) decreased intravenous opioid self-administration and the reinstatement of opioid-seeking behavior, an animal model of relapse, in rats...Additionally, we found that GLP-1Rs are expressed on GABAergic neurons on the IPN, providing a potential mechanism for Ex-4's effect on opioid seeking. Overall, these results support a functional role of IPN GLP-1R activation in Ex-4's effect on opioid seeking and support the use of GLP-1R agonists as a potential treatment for opioid use disorders.; Grant Support: NIDA Grant DA037897; NIDA Grant DA045792
- |||||||||| fentanyl citrate / Generic mfg.
Elevated depressive- and anxiety-like behaviors with prolonged abstinence from intermittent fentanyl self-administration (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_6989;
Early data show that these behaviors are correlated to post-access fentanyl motivation, which was elevated at 30d of abstinence, and that fentanyl motivation predicts relapse behavior, such that the highest-motivated rats show greater relapse when re-exposed to the SA chamber. These results confirm that IntA induces an expansive addiction-like state including depressive- and anxiety-like behaviors, pointing to its value as a preclinical model of OUD; that a negative emotional state arises with abstinence from opioids; and that drug motivation assessed with BE can predict this state and relapse propensity.; Grant Support: R01 DA006214
- |||||||||| fentanyl citrate / Generic mfg.
Role of orexin-1 receptor signaling in demand for the opioid fentanyl in adult females (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_6988;
Further analysis will be performed to elucidate the role of estrous cycle in fentanyl seeking female rats. In conclusion, our study supports OxR1 antagonist as a potential pharmacotherapy for opioid addiction in women.; Grant Support: National Institute On Alcohol Abuse And Alcoholism of the National Institutes of Health under Award Number T32AA028254
- |||||||||| fentanyl citrate / Generic mfg.
Transcriptomic adaptations in emotional and sensory brain nuclei in perinatal fentanyl exposed rodents (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_6965;
We identified upstream transcriptional programs and hub genes that could mediate the lasting behavioral changes in fentanyl use. Collectively, our studies are identifying unique gene expression adaptations across multiple brain regions relevant for lasting behaviors observed in perinatal fentanyl exposed mice.; Grant Support: 5R21DA048554-02
- |||||||||| fentanyl citrate / Generic mfg., morphine sulphate / Generic mfg.
Interleukin-1 receptor-associated kinase 4 (IRAK4) in the nucleus accumbens regulates opioid-seeking behavior (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_6847;
In addition, inhibition of IRAK4 also reduced the cue-induced reinstatement of fentanyl-seeking. Our findings suggest an important role of IRAK4 in opioids relapse-like behaviors and provide novel evidence in the association between innate immunity and drug addiction.; Grant Support: NIDA Grant R21DA040777; NIDA Grant R01DA047967
- |||||||||| fentanyl citrate / Generic mfg.
Fentanyl self-administration by rats engages the central nucleus of the amygdala (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_6765;
To probe the role of specific CeA transmitters previously implicated in appetitive processes, we microinfused either the opioid receptor antagonist, naltrexone, the 5-HT 2 receptor agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI), or the dopamine receptor antagonist, flupenthixol, prior to self-administration sessions...None of these effects interacted with sex. Taken together, these results demonstrate that the CeA is engaged by fentanyl self-administration when subjects have been trained under conditions that do not typically induce strong dependence.; Grant Support: R01DA035943
- |||||||||| Olinvyk (oliceridine) / Trevena, Jiangsu NHWA Pharma
Evaluation of Oliceridine as a high selectivity, low potency μOR radioligand for molecular imaging (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_6761;
To characterize the addiction-relevant behavioral response towards Oliceridine in an enhanced uptake condition, we are employing transgenic P-glycoprotein 1 knock-out mice in a conditioned place preference paradigm. Our results serve to facilitate the utilization of Oliceridine as a radioligand when co-administered with a P-gp blocker, enabling trace doses to bind to brain μOR with minimal G-protein recruitment.; Grant Support: NIDA IRP
- |||||||||| fentanyl citrate / Generic mfg.
Epigenome editing of nucleus accumbens cell subtype transcripts regulated by fentanyl abstinence (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_6605;
We have transfected these vectors along with Cre into Neuro2A cells and demonstrate upregulation of MSN subtype fentanyl abstinence regulated hub genes. We are currently packaging these vectors into AAVs to target NAc MSN subtypes, using D1-Cre and A2A-Cre mice, during opioid exposure and abstinence to determine if upregulating hub genes can influence MSN subtype/fentanyl abstinence gene expression networks.; Grant Support: R21DA052101
- |||||||||| fentanyl citrate / Generic mfg.
Neural circuits regulating opioid-induced motor hyperactivity and respiratory depression (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_5692;
In conclusion, our data showed that MORs mediate the effects of fentanyl on breathing and behaviours. Although SST is highly expressed in brainstem neurons that generate breathing, such as in the preBötzinger Complex, SST-expressing cells do not mediate the effects of fentanyl on breathing and behaviours.; Grant Support: Research was funded by the Canadian Institutes of Health Research and AF was supported by an Ontario Graduate Scholarship
- |||||||||| fentanyl citrate / Generic mfg., methadone / Generic mfg.
Truncating intracellular C-termini encoded by exon 7 of mu opioid receptor gene, Oprm1, in C57BL/6J mice attenuates fentanyl and methadone tolerance and reward (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_4868;
Fentanyl and methadone-induced β-arrestin2 recruitment in mMOR-1O, a full length E7-associated 7TM variant, was investigated in Be(2)C cells using with a Nanobit-based β-arrestin2 recruitment assay. Together, these data further support the functional relevance of E7-associated splice variants in opioid pharmacology.; Grant Support: NIH NIDA grant DA007242; The Peter F. McManus Trust; NIH NIDA grant DA042888; NIH CA08748; The Mayday Foundation; Rutgers Brain Health Institute; Rutgers New Jersey Medical School
- |||||||||| KRM-81 / RespireRx, NS16085 / Saniona
Antinociceptive effects of α 2 /α 3 -selective GABA A receptor positive allosteric modulators on opioid-induced hyperalgesia (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_4387;
This study systematically examined the antinociceptive effects of α 2 /α 3 -selective GABA A receptor PAMs alone and in combination with acetaminophen in an OIH rat model wherein repeated treatment with the opioid fentanyl induces mechanical hyperalgesia...Duration of actions of α 2 /α 3 -selective GABA A receptor PAMs (KRM-II-81, NS16085, HZ-166) alone were studied, and combinations of KRM-II-81 and acetaminophen were also studied at fixed ratios (1:1, 1:3, 3:1)...Furthermore, KRM-II-81/acetaminophen combinations produced additive to supra-additive interactions depending on the drug mixture ratios. These findings support the idea that α 2 /α 3 -selective GABA A receptor PAMs could serve as novel analgesics for treating OIH, and may interact favorably with other non-opioid analgesics.; Grant Support: NIH Grant DA047967
- |||||||||| fentanyl citrate / Generic mfg., ketamine / Generic mfg.
Environmental enrichment restores the long-lasting sequelae of perinatal fentanyl exposure (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_4234;
These results demonstrate that the lasting somatosensory-related effects of fentanyl can be reversed with a non-invasive intervention introduced during early development. These findings can inform ongoing efforts to develop actionable steps toward mitigating the consequences of opioid abuse among pregt women.; Grant Support: NIH/NINDS T32-NS063391; NIH/NIDA K99-DA050575; NIH/NIGMS T32-GM008181; Maryland MPowering the State; NIH/NIMH F31-MH123066; NIH/NIGMS R25-GM055036; NIH/NIDA F31-DA051113; NIH/NIDA R01-DA038613
- |||||||||| fentanyl citrate / Generic mfg.
Mu opioid receptor occupancy by intravenous naloxone in rat brain (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_1589;
In recent years, the United States has seen a drastic rise in opioid overdose deaths that has been fueled by synthetic opioids (e.g. fentanyl, carfentanil) flooding the illicit drug market...Together, these results suggest that clinically relevant doses of intravenous NLX are effective for acute reversal of opioid overdose but may be insufficient in preventing renarcotization due to the abolishment of their MOR antagonism 60 minutes post-treatment which was faster at the lower 0.4 mg HED dose. Moving forward, it is necessary to establish a more reliable, long-lasting method for opioid overdose reversal.; Grant Support: NIAAA Grant Y1AA-3009
- |||||||||| fentanyl citrate / Generic mfg., morphine sulphate / Generic mfg.
Characterization and opioid sensitivity of nucleus accumbens interneurons expressing neuropeptide y (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_1374;
All electrophysiological experiments were done in both male and female mice of 6-12 weeks in age. These data indicate that while LTSIs only comprise about 1% of neurons in the NAc they have opioid sensitive synaptic transmission that can alter the overall function of NAc circuitry.; Grant Support: NIH Grant 1R01DA048946-01
- |||||||||| fentanyl citrate / Generic mfg.
Angiotensin-converting enzyme non-canonically constrains opioid-sensitive synaptic transmission in nucleus accumbens (Virtual Only) - Dec 20, 2021 - Abstract #Neuroscience2021Neuroscience_23;
The physiological impact of ACE inhibition on striatal circuits is reflected in behavioral assays that demonstrated reduced conditioned place preference caused by fentanyl but increased reciprocal social interaction following captopril administration in female and male mice. These results provide preclinical evidence for a class of cardiovascular medications that could be repositioned and redesigned toward brain diseases characterized by aberrant striatal pathophysiology.; Grant Support: NIH Grant DA052109; NIH Grant DA048946; NIH Grant CA77598; NIH Grant MH122094; NIH Grant DA049476; NIH Grant DA050120
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