This article evaluates the effects of σ1-receptor inhibition on μ-opioid-induced mechanical antinociception and constipation. σ1-Knockout mice exhibited marked mechanical antinociception in response to μ-opioid analgesics at systemic doses that were inactive in wild-type mice and even unmasked the antinociceptive effects of the peripheral μ-opioid agonist loperamide. Likewise, treatment of wild-type mice with selective σ1 antagonists potentiated antinociception. These effects were fully reversed by treatment with a σ1 agonist. In contrast to its effects on nociception, σ1-receptor inhibition did not alter fentanyl- or loperamide-induced constipation, a peripherally mediated nonanalgesic opioid effect. Therefore, σ1-receptor inhibition may be used as a systemic or local adjuvant to enhanced peripheral μ-opioid analgesia without affecting opioid-induced constipation.
See article at J Pharmacol Exp Ther 2014, 348:32–45.
- Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics