scholarly journals EFFECTS OF NEW PIPERIDINE DERIVATIVES WITH SUBSTITUTIONS IN THE 1ST AND 4TH POSITIONS IN NALOXONE SENSITIVE ANALGESY

2021 ◽  
Vol 19 (5) ◽  
pp. 501-505
Author(s):  
A. A. Vasilyuk ◽  
◽  
V. I. Kozlovsky ◽  
G. S. Akhmetova ◽  
V. K. Yu ◽  
...  
Keyword(s):  
Pain Relief ◽  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Analgesic Effect ◽  
Chemical Stimulation ◽  
Analgesic Action ◽  
Preliminary Administration ◽  
Chemical Irritation

Background. Despite the wide arsenal of painkillers, pain relief is an urgent interdisciplinary problem that requires a search for new solutions. Purpose of the study. To establish the role of opioid receptors in the mechanism of the analgesic action of the piperidine derivatives AGV-22 and AGV-23. Material and methods. The studies were carried out on 96 white mice of both sexes weighing 30-40 g. The analgesic effect of the compounds was tested on models of thermal and chemical irritation with preliminary administration of the opioid receptor antagonist naloxone. Results. The pain reactions of mice with models of thermal and chemical stimulation in the AGV-22 / AGV-23 + naloxone and AGV-22 / AGV-23 groups were comparable. Conclusions. The mechanism of the analgesic action of the piperidine derivatives AGV-22 and AGV-23 is not associated with the activation of opioid receptors.

kappa-Opioid antagonist improves cellular bioenergetics and recovery after traumatic brain injury

1991 ◽  
Vol 261 (6) ◽  
pp. R1527-R1532 ◽  
Author(s):  
R. Vink ◽  
P. S. Portoghese ◽  
A. I. Faden
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Neurological Outcome ◽  
Kappa Opioid Receptors ◽  
Kappa Opioid ◽  
Opioid Receptor Antagonist ◽  
Cellular Bioenergetics

Treatment with opioid receptor antagonists improves outcome after experimental brain trauma, although the mechanisms underlying the protective actions of these compounds remain speculative. We have proposed that endogenous opioids contribute to the pathophysiology of traumatic brain injury through actions at kappa-opioid receptors, possibly by affecting cellular bioenergetic state. In the present study, the effects of the kappa-selective opioid-receptor antagonist nor-binaltorphimine (nor-BNI) were examined after fluid percussion brain injury in rats. Metabolic changes were evaluated by 31P magnetic resonance spectroscopy; the same animals were subsequently followed over 2 wk to evaluate neurological recovery. Nor-BNI, administered intravenously as a 10 or 20 mg/kg bolus at 30 min after injury, significantly improved neurological outcome at 2 wk posttrauma compared with controls. Animals treated with nor-BNI showed significantly greater recovery of intracellular free magnesium concentrations and cytosolic phosphorylation potentials during the first 4 h after injury compared with saline-treated controls. The improvement in cytosolic phosphorylation potential was significantly correlated to neurological outcome. These data support the hypothesis that kappa-opioid receptors mediate pathophysiological changes after traumatic brain injury and that the beneficial effects of opioid-receptor antagonist may result from improvement of posttraumatic cellular bioenergetics.

Morphine initiates migrating myoelectric complexes by acting on peripheral opioid receptors

1985 ◽  
Vol 249 (5) ◽  
pp. G557-G562 ◽  
Author(s):  
G. L. Telford ◽  
M. Hoshmonai ◽  
A. J. Moses ◽  
J. H. Szurszewski
Keyword(s):  
Opioid Receptor ◽  
Opioid Receptors ◽  
Silver Chloride ◽  
Phase Iii ◽  
Opioid Receptor Antagonists ◽  
Peripheral Opioid Receptors ◽  
Silver Silver ◽  
Silver Silver Chloride ◽  
Higher Doses

The role of peripheral and central opioid receptors in morphine-induced migrating myoelectric complexes (MMECs) was studied in conscious dogs implanted with silver-silver chloride electrodes. In normal fasted dogs morphine (100-200 micrograms/kg iv) initiated phase III of the MMEC in the duodenum. Once initiated the MMEC propagated distally. This effect of morphine was blocked by the opioid receptor antagonists naloxone (2 mg/kg iv) and N,N-diallylnormorphinium bromide (4 mg/kg iv). Higher doses of morphine (300-600 micrograms/kg iv) initiated phase III activity in fed dogs as early as 20 min after feeding, while lower doses (150 micrograms/kg iv) initiated phase III activity routinely when administered 100 min after feeding. In dogs with bilateral vagotomies and bilateral thoracolumbar sympathetic chain ganglionectomies, morphine (150 micrograms/kg iv) initiated phase III activity in the duodenum, which then migrated distally. This study demonstrates that morphine initiates phase III of the MMEC by acting through peripheral opioid receptors.

Protection of cardiac myocytes via δ1-opioid receptors, protein kinase C, and mitochondrial KATP channels

2001 ◽  
Vol 280 (1) ◽  
pp. H377-H383 ◽  
Author(s):  
Joon Huh ◽  
Garrett J. Gross ◽  
Hiroshi Nagase ◽  
Bruce T. Liang
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Receptor Antagonist ◽  
Cardiac Myocytes ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Inhibitory Effect ◽  
Cardioprotective Effect ◽  
Opioid Receptor Antagonist ◽  
Kinase C

The objective of the present study was to investigate the role of δ1-opioid receptors in mediating cardioprotection in isolated chick cardiac myocytes and to investigate whether protein kinase C and mitochondrial ATP-sensitive K+(KATP) channels act downstream of the δ1-opioid receptor in mediating this beneficial effect. A 5-min preexposure to the selective δ1-opioid receptor agonist (−)-TAN-67 (1 μM) resulted in less myocyte injury during the subsequent prolonged ischemia compared with untreated myocytes. 7-Benzylidenenaltrexone, a selective δ1-opioid receptor antagonist, completely blocked the cardioprotective effect of (−)-TAN-67. Naltriben methanesulfonate, a selective δ2-opioid receptor antagonist, had only a slight inhibitory effect on (−)-TAN-67-mediated cardioprotection. Nor-binaltorphimine dihydrochloride, a κ-opioid receptor antagonist, did not affect (−)-TAN-67-mediated cardioprotection. The protein kinase C inhibitor chelerythrine and the KATP channel inhibitors glibenclamide, a nonselective KATP antagonist, and 5-hydroxydecanoic acid, a mitochondrial selective KATPantagonist, reversed the cardioprotective effect of (−)-TAN-67. These results suggest that the δ1-opioid receptor is present on cardiac myocytes and mediates a potent cardioprotective effect via protein kinase C and the mitochondrial KATP channel.

scholarly journals Interferon-β suppresses inflammatory pain through activating µ-opioid receptor

2021 ◽  
Vol 17 ◽  
pp. 174480692110452
Author(s):  
Chien Cheng Liu ◽  
I Cheng Lu ◽  
Li Kai Wang ◽  
Jen Yin Chen ◽  
Yu Yu Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Western Blot ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Inflammatory Pain ◽  
Analgesic Effect ◽  
Intrathecal Injection ◽  
Type I ◽  
Withdrawal Threshold ◽  
Withdrawal Latency

Interferons (IFNs) are cytokines secreted by infected cells that can interfere with viral replication. Besides activating antiviral defenses, type I IFNs also exhibit diverse biological functions. IFN-β has been shown to have a protective effect against neurotoxic and inflammatory insults on neurons. Therefore, we aimed to investigate the possible role of IFN-β in reducing mechanical allodynia caused by Complete Freund’s Adjuvant (CFA) injection in rats. We assessed the antinociceptive effect of intrathecal IFN-β in naïve rats and the rats with CFA–induced inflammatory pain. After the behavioral test, the spinal cords of the rats were harvested for western blot and immunohistochemical double staining. We found that intrathecal administration of IFN-β in naïve rats can significantly increase the paw withdrawal threshold and paw withdrawal latency. Further, the intrathecal injection of a neutralizing IFN-β antibody can reduce the paw withdrawal threshold and paw withdrawal latency, suggesting that IFN-β is produced in the spinal cord in normal conditions and serves as a tonic inhibitor of pain. In addition, intrathecal injection of IFN-β at dosages from 1000 U to 10000 U demonstrates a significant transient dose-dependent inhibition of CFA-induced inflammatory pain. This analgesic effect is reversed by intrathecal naloxone, suggesting that IFN-β produces an analgesic effect through central opioid receptor-mediated signaling. Increased expression of phospho-µ-opioid receptors after IFN-β injection was observed on western blot, and immunohistochemical staining showed that µ-opioids co-localized with IFN-α/βR in the dorsal horn of the spinal cord. The findings of this study demonstrate that the analgesic effect of IFN-β is through µ-opioid receptors activation in spial cord.

scholarly journals GRKs as Key Modulators of Opioid Receptor Function

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2400
Author(s):  
Laura Lemel ◽  
J Robert Lane ◽  
Meritxell Canals
Keyword(s):  
Opioid Receptor ◽  
Opioid Receptors ◽  
Opioid Analgesics ◽  
Mu Opioid ◽  
Protein Receptor ◽  
The Family ◽  
Receptor Kinases ◽  
Induced Tolerance ◽  
Shed Light

Understanding the link between agonist-induced phosphorylation of the mu-opioid receptor (MOR) and the associated physiological effects is critical for the development of novel analgesic drugs and is particularly important for understanding the mechanisms responsible for opioid-induced tolerance and addiction. The family of G protein receptor kinases (GRKs) play a pivotal role in such processes, mediating phosphorylation of residues at the C-tail of opioid receptors. Numerous strategies, such as phosphosite specific antibodies and mass spectrometry have allowed the detection of phosphorylated residues and the use of mutant knock-in mice have shed light on the role of GRK regulation in opioid receptor physiology. Here we review our current understanding on the role of GRKs in the actions of opioid receptors, with a particular focus on the MOR, the target of most commonly used opioid analgesics such as morphine or fentanyl.

Synaptic Actions of Neuropeptide FF in the Rat Parabrachial Nucleus: Interactions With Opioid Receptors

2000 ◽  
Vol 84 (2) ◽  
pp. 744-751 ◽  
Author(s):  
Xihua Chen ◽  
Jeffrey A. Zidichouski ◽  
Kim H. Harris ◽  
Jack H. Jhamandas
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Distribution Curve ◽  
Parabrachial Nucleus ◽  
Synaptic Currents ◽  
Opioid Receptor Antagonist ◽  
Neuropeptide Ff ◽  
Δ Opioid Receptor ◽  
Synaptic Effects

The pontine parabrachial nucleus (PBN) receives both opioid and Neuropeptide FF (NPFF) projections from the lower brain stem and/or the spinal cord. Because of this anatomical convergence and previous evidence that NPFF displays both pro- and anti-opioid activities, this study examined the synaptic effects of NPFF in the PBN and the mechanisms underlying these effects using an in vitro brain slice preparation and the nystatin-perforated patch-clamp recording technique. Under voltage-clamp conditions, NPFF reversibly reduced the evoked excitatory postsynaptic currents (EPSCs) in a dose-dependent fashion. This effect was not accompanied by apparent changes in the holding current, the current-voltage relationship or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid–induced inward currents in the PBN cells. When a paired-pulse protocol was used, NPFF increased the ratio of these synaptic currents. Analysis of miniature EPSCs showed that NPFF caused a rightward shift in the frequency-distribution curve, whereas the amplitude-distribution curve remained unchanged. Collectively, these experiments indicate that NPFF reduces the evoked EPSCs through a presynaptic mechanism of action. The synaptic effects induced by NPFF (5 μM) could not be blocked by the specific μ-opioid receptor antagonist,d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2(1 μM), but application of δ-opioid receptor antagonist Tyr-Tic-Phe-Phe (5 μM) almost completely prevented effects of NPFF. Moreover, the δ-opioid receptor agonist, Deltorphin (1 μM), mimicked the effects as NPFF and also occluded NPFF's actions on synaptic currents. These results indicate that NPFF modulates excitatory synaptic transmission in the PBN through an interaction with presynaptic δ-opioid receptors. These observations provide a cellular basis for NPFF enhancement of the antinociceptive effects consequent to central activation of δ-opioid receptors.

The Analgesic Mechanism of Processed Aconiti Tuber: The Involvement of Descending Inhibitory System

1994 ◽  
Vol 22 (01) ◽  
pp. 83-94 ◽  
Author(s):  
Tomoko Isono ◽  
Tsutomu Oyama ◽  
Akitoshi Asami ◽  
Yasuyuki Suzuki ◽  
Yuki Hayakawa ◽  
...  
Keyword(s):  
Oral Administration ◽  
Cold Stress ◽  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Analgesic Effect ◽  
Intraperitoneal Administration ◽  
Inhibitory System ◽  
Antinociceptive Action ◽  
Opioid Receptor Antagonist ◽  
Rcs Rats

Tsumura-shuchi-bushi-matsu (TJ-3021) is a processed Aconiti tuber which has a potent antinociceptive action. The present study was undertaken to study the analgesic mechanism produced by TJ-3021. RCS (repeated cold stress) rats in hyperalgesia were markedly suppressed by oral administration of TJ-3021. Intrathecal and intraperitoneal administration of a selective α2-adrenoreceptor antagonist, idazoxan (IDA), reduced significantly the analgesic effect of TJ-3021 in RCS rats. Methysergide (METH), a 5-HT receptor antagonist, demonstrated a similar effect, while intraperitoneal administration of opioid receptor antagonist, naloxone, did not produce the effect. Both oral and intracisternal administration of mesaconitine (MA) which is one of the main potent alkaloids contained in TJ-3021 produced analgesic effect in non-RCS rats.

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