scholarly journals Biphalin—A Potent Opioid Agonist—As a Panacea for Opioid System-Dependent Pathophysiological Diseases?

2021 ◽  
Vol 22 (21) ◽  
pp. 11347
Author(s):  
Patrycja Redkiewicz ◽  
Jolanta Dyniewicz ◽  
Aleksandra Misicka
Keyword(s):  
Opioid Receptors ◽  
Biological Effects ◽  
Antinociceptive Effect ◽  
Opioid System ◽  
Opioid Agonist ◽  
Physiological Functions ◽  
Animal Pain ◽  
Neuronal Tissues ◽  
The Central Nervous System ◽  
Analgesic Peptide

Biphalin, one of the opioid agonists, is a dimeric analog of enkephalin with a high affinity for opioid receptors. Opioid receptors are widespread in the central nervous system and in peripheral neuronal and non-neuronal tissues. Hence, these receptors and their agonists, which play an important role in pain blocking, may also be involved in the regulation of other physiological functions. Biphalin was designed and synthesized in 1982 by Lipkowski as an analgesic peptide. Extensive further research in various laboratories on the antinociceptive effects of biphalin has shown its excellent properties. It has been demonstrated that biphalin exhibits an analgesic effect in acute, neuropathic, and chronic animal pain models, and is 1000 times more potent than morphine when administered intrathecally. In the course of the broad conducted research devoted primarily to the antinociceptive effect of this compound, it has been found that biphalin may also potentially participate in the regulation of other opioid system-dependent functions. Nearly 40 years of research on the properties of biphalin have shown that it may play a beneficial role as an antiviral, antiproliferative, anti-inflammatory, and neuroprotective agent, and may also affect many physiological functions. This integral review analyzes the literature on the multidirectional biological effects of biphalin and its potential in the treatment of many opioid system-dependent pathophysiological diseases.

scholarly journals Heparin sensitization of fentanyl initiated mu-receptors

2021 ◽  
pp. 20-32
Author(s):  
А.Е. Khomutov ◽  
◽  
А.V. Deryugina ◽  
А.S. Lizunova ◽  
Z.V. Bobrova ◽  
...  
Keyword(s):  
Opioid Receptors ◽  
Anticoagulant Activity ◽  
Antinociceptive Effect ◽  
Regulatory Peptides ◽  
Tail Flick ◽  
Mu Opioid Receptors ◽  
Opioid Agonist ◽  
Hypotensive Action ◽  
Tail Flick Test ◽  
Mu Opioid

Heparin is an anticoagulant widely used in clinical practice. In addition to anticoagulant activity, heparin has a cytostatic, bacteriostatic, antilipemic, radioprotective effect, and exhibits antiallergic and hypotensive action. Heparin modulates cardiotropic, neurotropic, antihypoxic, anti-ischemic properties of regulatory peptides and pharmacological agents used in pain relief and anesthesia. At the same time, there is very little information about the antinociceptive effect of heparin. The aim of this work is to study the effect of heparin in combination with the opioid agonist fentanyl on mu-opioid receptors at the spinal and supraspinal levels. In experiments on laboratory rats, it was established that heparin, when pre-administered and combined with fentanyl, increases the latency in the tail flick test and the paw licking test. Naloxone, an opioid receptor antagonist, reduces antinociceptive efficacy of the studied compounds. Protamine sulfate also reduces the level of heparin sensitization of opioid receptors. Thus, the obtained data allow us to speak about the sensitizing effect of heparin on initiated by an agonist mu-opioid receptors at the spinal and supraspinal levels.

scholarly journals Renal effects of opioid exposure: Considerations for therapeutic use

2006 ◽  
Vol 2 (4) ◽  
pp. 236 ◽  
Author(s):  
Kalpna Gupta, PhD ◽  
Marc L. Weber, MD
Keyword(s):  
Kidney Function ◽  
Opioid Receptors ◽  
Renal Physiology ◽  
Acute Effects ◽  
Opioid Agonist ◽  
Collapsing Glomerulopathy ◽  
Renal Changes ◽  
The Central Nervous System ◽  
Salt And Water Balance ◽  
Peripheral Opioid Receptors

In recent years, the discovery of peripheral opioid receptors has challenged the dogma of opioids interacting exclusively with the central nervous system. In this article, we describe the current understanding of the roles of opioids and opioid receptors in renal physiology and pathophysiology. The renal response to opioid exposure varies depending upon the specific opioid agonist, dose, and duration of exposure. The known acute effects of opioids on the kidney impact salt and water balance. The chronic effects of opioid exposure on kidney function are largely unknown, but collapsing glomerulopathy has been associated with chronic heroin abuse. Opioid exposure can lead to both physiological and architectural renal changes, and this may have important clinical implications. Since opioids are often used for pain management in patients with existing kidney disease, their role in kidney function warrants attention.

scholarly journals Clinical, behavioral and antinociceptive effects of crotalphine in horses

2015 ◽  
Vol 46 (4) ◽  
pp. 694-699
Author(s):  
Erica Cristina Bueno do Prado Guirro ◽  
João Henrique Perotta ◽  
Márcio de Paula ◽  
Yara Cury ◽  
Carlos Augusto Araújo Valadão
Keyword(s):  
Inflammatory Pain ◽  
Antinociceptive Effect ◽  
Behavioral Changes ◽  
Behavioral Effects ◽  
Phase Iii ◽  
Intact Skin ◽  
Kappa Opioid ◽  
Antinociceptive Effects ◽  
Analgesic Peptide ◽  
Scapular Region

ABSTRACT: Crotalphine is a novel analgesic peptide that acts on kappa opioid and delta receptors, causing powerful analgesia in rats submitted to inflammatory, neuropathic or oncologic models of pain. This study evaluated clinical, behavioral and antinociceptive effects caused by crotalphine in horses, employing 18 Arabian horses and it was divided in three phases. In Phase I, "clinical and behavioral effects", crotalphine did not change the latency to urinate and defecate; did not modify the values of cardiac or respiratory rates, intestinal motility and rectal temperature; and did not cause significant ataxia, head, eye and lip ptosis. In Phase II, "antinociceptive effect on intact skin at scapular or ischial region", crotalphine did not cause significant analgesia. In Phase III, "antinociceptive effect on incised skin at scapular or ischial region", crotalphine promoted effective antinociceptive effects for six hours and inhibited hyperalgesia state for three days in the ischial region of horses submitted to incisional model of inflammatory pain, but crotalphine did not evoke relevant analgesic effect on the scapular region. Concluding, intravenous injection of a single dose of crotalphine (3.8ngkg-1) did not cause important clinical or behavioral changes and promotes antinociceptive effect on incised ischial region for seven days in horses. Moreover, crotalphine did not evoke relevant anti nociceptive effect on the scapular region or in intact skin of horses.

Microglia extracellular vesicles: focus on molecular composition and biological function

2021 ◽  
Vol 49 (4) ◽  
pp. 1779-1790 ◽  
Author(s):  
Lorenzo Ceccarelli ◽  
Chiara Giacomelli ◽  
Laura Marchetti ◽  
Claudia Martini
Keyword(s):  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Biological Function ◽  
Biological Effects ◽  
Genetic Material ◽  
Cell Communication ◽  
Molecular Composition ◽  
Cargo Proteins ◽  
A Cell ◽  
The Central Nervous System

Extracellular vesicles (EVs) are a heterogeneous family of cell-derived lipid bounded vesicles comprising exosomes and microvesicles. They are potentially produced by all types of cells and are used as a cell-to-cell communication method that allows protein, lipid, and genetic material exchange. Microglia cells produce a large number of EVs both in resting and activated conditions, in the latter case changing their production and related biological effects. Several actions of microglia in the central nervous system are ascribed to EVs, but the molecular mechanisms by which each effect occurs are still largely unknown. Conflicting functions have been ascribed to microglia-derived EVs starting from the neuronal support and ending with the propagation of inflammation and neurodegeneration, confirming the crucial role of these organelles in tuning brain homeostasis. Despite the increasing number of studies reported on microglia-EVs, there is also a lot of fragmentation in the knowledge on the mechanism at the basis of their production and modification of their cargo. In this review, a collection of literature data about the surface and cargo proteins and lipids as well as the miRNA content of EVs produced by microglial cells has been reported. A special highlight was given to the works in which the EV molecular composition is linked to a precise biological function.

Role of the NO-cGMP-K+ channels pathway in the peripheral antinociception induced by α-bisabolol

2021 ◽  
Author(s):  
Mario I Ortiz ◽  
Raquel Cariño-Cortés ◽  
Victor Manuel Muñoz Pérez ◽  
Andres Salas Casas ◽  
Gilberto Castañeda-Hernández
Keyword(s):  
Opioid Receptors ◽  
Formalin Test ◽  
Antinociceptive Effect ◽  
Dorsal Surface ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
K Channel ◽  
Formalin Injection ◽  
K Channels ◽  
The Right

The aim of this study was to examine if the peripheral antinociception of α-bisabolol involve the participation of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) synthesis followed by K+ channel opening in the formalin test. Wistar rats were injected in the dorsal surface of the right hind paw with formalin (1%). Rats received a subcutaneous injection into the dorsal surface of the paw of vehicles or increasing doses of α-bisabolol (100-300 µg/paw). To determine whether the peripheral antinociception induced by α-bisabolol was mediated by either the opioid receptors or the NO-cGMP-K+ channels pathway, the effect of pretreatment (10 min before formalin injection) with the appropriate vehicles, naloxone, naltrexone, L-NAME, ODQ, glibenclamide, glipizide, apamin, charybdotoxin, tetraethylammonium or 4-aminopyridine on the antinociceptive effects induced by local peripheral α-bisabolol (300 µg/paw) were assessed. α-bisabolol produced antinociception during both phases of the formalin test. α-bisabolol antinociception was blocked by L-NAME, ODQ, and all the K+ channels blockers. The peripheral antinociceptive effect produced by α-bisabolol was not blocked by the opioid receptor inhibitors. α-bisabolol was able to active the NO-cGMP-K+ channels pathway in order to produce its antinoceptive effect. The participation of opioid receptors in the peripheral local antinociception induced by α-bisabolol is excluded.

scholarly journals Morphine Antinociception Restored by Use of Methadone in the Morphine-Resistant Inflammatory Pain State

2020 ◽  
Vol 11 ◽  
Author(s):  
Chizuko Watanabe ◽  
Asami Komiyama ◽  
Masaru Yoshizumi ◽  
Shinobu Sakurada ◽  
Hirokazu Mizoguchi
Keyword(s):  
Opioid Receptors ◽  
Inflammatory Pain ◽  
Antinociceptive Effect ◽  
Thermal Hyperalgesia ◽  
Expression Level ◽  
Pain Model ◽  
Mk 801 ◽  
Antinociceptive Effects ◽  
Pain State ◽  
Intraperitoneal Treatment

The antinociceptive effect of methadone in the morphine-resistant inflammatory pain state was described in the paw-withdrawal test using the complete Freund’s adjuvant (CFA)-induced mouse inflammatory pain model. After intraplantar (i.pl.) injection of CFA, thermal hyperalgesia was observed in the ipsilateral paw. The antinociceptive effects of subcutaneous (s.c.) injection of morphine, fentanyl, and oxycodone against thermal hyperalgesia in the inflammatory pain state were reduced in the ipsilateral paw 7 days after CFA pretreatment. On the contrary, the antinociceptive effect of s.c. injection of methadone was maintained in the ipsilateral paw 7 days after CFA pretreatment. The suppressed morphine antinociception in the CFA model mice was bilaterally restored following s.c. treatment with methadone 20 min prior to or 3 days after CFA pretreatment. The suppressed morphine antinociception was also bilaterally restored by intraperitoneal treatment with MK-801 30 min prior to CFA pretreatment; however, the s.c. injection of morphine 30 min prior to CFA pretreatment failed to restore the suppressed morphine antinociception in the CFA model mice. The expression level of mRNA for µ-opioid receptors 7 days after i.pl. pretreatment was not significantly changed by i.pl. pretreatment with CFA or s.c. pretreatment with methadone. In conclusion, methadone is extremely effective against thermal hyperalgesia in the morphine-resistant inflammatory pain state, and restores suppressed morphine antinociception in the inflammatory pain state without altering the expression level of mRNA for µ-opioid receptors.

Stereostructure-activity relationship of opioid agonist and antagonist bivalent ligands. Evidence for bridging between vicinal opioid receptors

1985 ◽  
Vol 28 (9) ◽  
pp. 1140-1141 ◽  
Author(s):  
P. S. Portoghese ◽  
D. L. Larson ◽  
C. B. Yim ◽  
L. M. Sayre ◽  
G. Ronsisvalle ◽  
...  
Keyword(s):  
Opioid Receptors ◽  
Activity Relationship ◽  
Bivalent Ligands ◽  
Opioid Agonist ◽  
Agonist And Antagonist ◽  
Relationship Of
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