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Updated: May 24, 2026

The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice
Published on: July 16, 2014
Low brain penetrant CB1 receptor agonists for the treatment of neuropathic pain
Julia M Adam1, John K Clark, Keneth Davies
1Department of Chemistry, Merck Research Laboratories, MSD, Newhouse, Lanarkshire, UK. julia1adam@gmail.com
Abstract:
Novel, low brain penetrant, orally bioavailable CB1 receptor agonists were designed starting from a mature lead series of potent brain penetrant CB1 receptor agonists. Increasing the calculated polar surface area was found to be a good strategy for reducing brain penetration whilst retaining drug-like properties. This in silico approach led to the discovery of LBP1, an orally bioavailable, low brain penetrant CB1 receptor agonist with robust activity in rodent models of neuropathic pain and a good preclinical therapeutic profile, which was selected for clinical development.
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