In vitro abuse liability and off-target safety

• In vitro functional screen

Pharmacokinetics

• Protein binding
• Pharmacokinetics

Side effect profile

• Modified Irwin functional observational battery
• Rotarod

Pain models

• Plantar incision
• L5/L6 spinal nerve ligation (SNL)
• Monosodium iodoacetate (MIA)
• Paclitaxel chemotherapy-induced peripheral neuropathy (CIPN)
• Oxaliplatin chemotherapy-induced peripheral neuropathy (CIPN)

Validated endpoints

• Hind paw mechanical allodynia behavior (von Frey filaments)
• Hind paw cold allodynia (acetone evaporation) test
• Guarding behavior
• Dynamic weight bearing

In vivo abuse liability

• Intravenous self-administration
• Conditioned place preference (CPP)