In vivo evaluation of (+)-MR200 as a new selective sigma ligand modulating MOP, DOP and KOP supraspinal analgesia

Marrazzo, Agostino; Parenti, Carmela; Scavo, Valentina; Ronsisvalle, Simone; Scoto, G.M.; Ronsisvalle, Giuseppe

doi:10.1016/j.lfs.2005.10.005

Cited by 39 publications

(38 citation statements)

References 24 publications

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“…A dose as low as 2 mg/kg naloxone methiodide was enough to completely abolish the opioid antinociception induced by all m agonists tested, not only in WT mice treated locally with a s 1 antagonist (in which its effects are clearly peripherally mediated), but also in s 1 -KO mice or WT mice treated systemically with the s 1 antagonists. This does not argue against the widely reported potentiation of opioid antinociception by central s 1 receptor inhibition (King et al, 1997;Pan et al, 1998;Pasternak, 2002, 2007;Marrazzo et al, 2006) but indicates that, when both opioid agonism and s 1 inhibition are induced systemically, the increase in antinociception occurs mainly at the peripheral level. In support of the peripheral location of these modulatory effects of s 1 receptors, we found much higher levels of these receptors in the DRG than in several areas of the central nervous system that play a key role in opioid antinociception.…”

Section: Modulation Of Peripheral M-opioidmentioning

confidence: 57%

“…However, s 1 inhibition is able to enhance opioid signaling (Kim et al, 2010) and to potentiate the antinociceptive effect of systemic opioids Pasternak, 1993, 1994;Marrazzo et al, 2011;Sánchez-Fernández et al, 2013;Vidal-Torres et al, 2013). Opioid antinociception can be potentiated by central s 1 inhibition (King et al, 1997;Pan et al, 1998;Pasternak, 2002, 2007;Marrazzo et al, 2006), and we recently reported that the local peripheral coadministration of s 1 antagonists and morphine also resulted in markedly enhanced antinociception (Sánchez-Fernández et al, 2013). However, it is unknown whether peripheral mechanisms are involved in the antinociception induced by systemic opioids when s 1 receptors are inhibited.…”

Section: Introductionmentioning

confidence: 99%

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Modulation of Peripheralμ-Opioid Analgesia byσ₁Receptors

Sánchez-Fernández

Montilla-García

González‐Cano

et al. 2013

J Pharmacol Exp Ther

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We evaluated the effects of s 1 -receptor inhibition on m-opioidinduced mechanical antinociception and constipation. s 1 -Knockout mice exhibited marked mechanical antinociception in response to several m-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 m-opioid agonist loperamide. Likewise, systemic (subcutaneous) or local (intraplantar) treatment of wild-type mice with the selective A peripheral role for s 1 receptors was also supported by their higher density (Western blot results) in peripheral nervous tissue (dorsal root ganglia) than in several central areas involved in opioid antinociception (dorsal spinal cord, basolateral amygdala, periaqueductal gray, and rostroventral medulla). In contrast to its effects on nociception, s 1 -receptor inhibition did not alter fentanyl-or loperamide-induced constipation, a peripherally mediated nonanalgesic opioid effect. Therefore, s 1 -receptor inhibition may be used as a systemic or local adjuvant to enhance peripheral m-opioid analgesia without affecting opioidinduced constipation.

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Section: Modulation Of Peripheral M-opioidmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Modulation of Peripheralμ-Opioid Analgesia byσ₁Receptors

Sánchez-Fernández

Montilla-García

González‐Cano

et al. 2013

J Pharmacol Exp Ther

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“…Nociception was evaluated by the radiant heat tail-flick test (Marrazzo et al, 2006). Briefly, this consisted of irradiation of the lower third of the tail with an infrared source (Ugo Basile, Comerio, Italy).…”

Section: Nociceptive Testmentioning

confidence: 99%

A new sigma ligand, (±)-PPCC, antagonizes kappa opioid receptor-mediated antinociceptive effect

et al. 2008

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“…Sigma receptors have been reported to play an important role in the modulation of analgesia produced by µ-, δ-or κ-opioid receptor agonists (Mei and Pasternak, 2002;Marrazzo et al, 2006;Chien and Pasternak, 1994). (+)-Pentazocine antagonizes (−)-morphine-produced analgesia, which is reversed by sigma receptor antagonist haloperidol (Chien and Pasternak, 1993).…”

Section: Introductionmentioning

confidence: 99%

Stereoselective action of (+)-morphine over (−)-morphine in attenuating the (−)-morphine-produced antinociception via the naloxone-sensitive sigma receptor in the mouse

Hong

Tseng

2007

European Journal of Pharmacology

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We have previously demonstrated that (+)-morphine and (−)-morphine given spinally stereoselectively attenuate the spinally-administered (−)-morphine-produced tail-flick inhibition in the mouse. The phenomenon has been defined as antianalgesia (Wu et al., 2005). Present studies were then undertaken to determine if the systemic administration of (+)-morphine and (−)-morphine also stereoselectively attenuates the systemic (−)-morphine-produced tail-flick inhibition and the effects of (+)-morphine and (−)-morphine are mediated by the naloxone-sensitive sigma receptor activation in male CD-1 mice. Pretreatment with (+)-morphine at a dose of 0.01-10 ng/kg given subcutaneously dose-dependently attenuated the tail-flick inhibition produced by subcutaneouslyadministered (−)-morphine (5 mg/kg). Pretreatment with (−)-morphine (0.01-1.0 mg/kg) given subcutaneously also attenuates the (−)-morphine-produced tail-flick inhibition. The ED 50 values for (+)-morphine and (−)-morphine for inhibiting the (−)-morphine-produced tail-flick inhibition were estimated to be 30.6 pg/kg and 97.5 µg/kg, respectively. The attenuation of the (−)-morphineproduced tail-flick inhibition induced by (+)-morphine or (−)-morphine pretreatment was reversed by the pretreatment with (+)-naloxone or by the sigma receptor antagonist BD1047 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine dihydrobromide) given subcutaneously. Pretreatment with (+)-pentazocine, a selective sigma receptor agonist, (1-10 mg/ kg) given subcutaneously also attenuates (−)-morphine-produced tail-flick inhibition, which was restored by (+)-naloxone (4 mg/kg) or BD1047 (10 mg/kg) pretreated subcutaneously. It is concluded that (+)-morphine exhibits extremely high stereoselective action over (−)-morphine given systemically in attenuating the systemic (−)-morphine-produced antinociception and the antianalgesic effect of (+)-morphine and (−)-morphine is mediated by activation of the naloxonesensitive sigma receptor.

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In vivo evaluation of (+)-MR200 as a new selective sigma ligand modulating MOP, DOP and KOP supraspinal analgesia

Cited by 39 publications

References 24 publications

Modulation of Peripheralμ-Opioid Analgesia byσ₁Receptors

Modulation of Peripheralμ-Opioid Analgesia byσ₁Receptors

A new sigma ligand, (±)-PPCC, antagonizes kappa opioid receptor-mediated antinociceptive effect

Stereoselective action of (+)-morphine over (−)-morphine in attenuating the (−)-morphine-produced antinociception via the naloxone-sensitive sigma receptor in the mouse

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In vivo evaluation of (+)-MR200 as a new selective sigma ligand modulating MOP, DOP and KOP supraspinal analgesia

Cited by 39 publications

References 24 publications

Modulation of Peripheralμ-Opioid Analgesia byσ1Receptors

Modulation of Peripheralμ-Opioid Analgesia byσ1Receptors

A new sigma ligand, (±)-PPCC, antagonizes kappa opioid receptor-mediated antinociceptive effect

Stereoselective action of (+)-morphine over (−)-morphine in attenuating the (−)-morphine-produced antinociception via the naloxone-sensitive sigma receptor in the mouse

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Modulation of Peripheralμ-Opioid Analgesia byσ₁Receptors

Modulation of Peripheralμ-Opioid Analgesia byσ₁Receptors