Positive Allosteric Modulation of Cannabinoid Receptor Type 1 Suppresses Pathological Pain Without Producing Tolerance or Dependence.

ABSTRACT:

Background

Activation of cannabinoid CB₁ receptors suppresses pathological pain but also produces unwanted central side effects. We hypothesized that a positive allosteric modulator of CB₁ signaling would suppress inflammatory and neuropathic pain without producing cannabimimetic effects or physical dependence. We also asked whether a CB₁ positive allosteric modulator would synergize with inhibitors of endocannabinoid deactivation and/or an orthosteric cannabinoid agonist.

Methods

GAT211, a novel CB₁ positive allosteric modulator, was evaluated for antinociceptive efficacy and tolerance in models of neuropathic and/or inflammatory pain. Cardinal signs of direct CB₁-receptor activation were evaluated together with the pro

SUBMITTER: Slivicki RA 

PROVIDER: S-EPMC5758437 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature