Modulation of Peripheral μ-Opioid Analgesia by σ1 Receptors

  title={Modulation of Peripheral $\mu$-Opioid Analgesia by $\sigma$1 Receptors},
  author={Cristina S{\'a}nchez-Fern{\'a}ndez and {\'A}ngeles Montilla-Garc{\'i}a and Rafael C. Gonz{\'a}lez-Cano and Francisco Rafael Nieto and Luc{\'i}a Romero and Antonia Artacho-Cord{\'o}n and Rosa Montes and Bego{\~n}a Fern{\'a}ndez-Pastor and Manuel Merlos and Jose M. Baeyens and Jos{\'e} Manuel Entrena and Enrique J. Cobos},
  journal={The Journal of Pharmacology and Experimental Therapeutics},
  pages={32 - 45}
We evaluated the effects of σ1-receptor inhibition on μ-opioid–induced mechanical antinociception and constipation. σ1-Knockout mice exhibited marked mechanical antinociception in response to several μ-opioid analgesics (fentanyl, oxycodone, morphine, buprenorphine, and tramadol) at systemic (subcutaneous) doses that were inactive in wild-type mice and even unmasked the antinociceptive effects of the peripheral μ-opioid agonist loperamide. Likewise, systemic (subcutaneous) or local… 
New Morphine Analogs Produce Peripheral Antinociception within a Certain Dose Range of Their Systemic Administration
Systemic administration of the novel compound 14-O-MeM6SU similar to M6SU in specific dose ranges shows peripheral antinociceptive effects in rat and mouse inflammatory pain models without central adverse effects, suggesting titration of systemic doses of opioid compounds with limited access to the brain might offer peripheral ant inociception of clinical importance.
Synthesis and Biological Evaluation of Novel σ1 Receptor Ligands for Treating Neuropathic Pain: 6-Hydroxypyridazinones.
By use of the 6-hydroxypyridazinone framework, a new series of potent σ1 receptor ligands associated with pharmacological antineuropathic pain activity was synthesized and is described in this
Supraspinal and Peripheral, but Not Intrathecal, σ1R Blockade by S1RA Enhances Morphine Antinociception
The site of action of σ1R for opioid modulation on acute thermal nociception is located at the peripheral and supraspinal levels, and the opioid-potentiating effect is independent of the spinal noradrenaline increase produced by S1RA.
Development of New Benzylpiperazine Derivatives as σ1 Receptor Ligands with in Vivo Antinociceptive and Anti-Allodynic Effects
A new series of benzylpiperazine-based σ1R antagonists has been designed, synthesized, and characterized for their affinities toward ρ1R and selectivity over the σ-2 receptor (σ2R).
Sigma-1 Receptor Antagonists: A New Class of Neuromodulatory Analgesics.
Sigma-1 antagonists (in the absence of opioids) have been shown to exert antinociceptive effects in preclinical models of neuropathic pain induced by nerve trauma or chemical injury, and more recently in inflammatory and ischemic pain.


Opioid antinociception in a rat model of visceral pain: systemic versus local drug administration.
It is suggested that opioid delta receptors may be present on bladder nociceptive afferents and may be activated for production of peripheral analgesia.
Potentiation of morphine-induced mechanical antinociception by σ1 receptor inhibition: Role of peripheral σ1 receptors
Antinociceptive profile of LP1, a non-peptide multitarget opioid ligand.
Analgesic effects of morphine and loperamide in the rat formalin test: interactions with NMDA receptor antagonists.
Morphine and ABT-594 (a nicotinic acetylcholine agonist) exert centrally mediated antinociception in the rat cyclophosphamide cystitis model of visceral pain.
Selective antagonism of opioid analgesia by a sigma system.
  • C. Chien, G. Pasternak
  • Biology, Psychology
    The Journal of pharmacology and experimental therapeutics
  • 1994
Sigma 1 systems functionally antagonize opioid analgesia without affecting morphine's effects on gastrointestinal transit or lethality, and the antiopioid sigma system is tonically active and is more active against kappa analgesia than mu.