In vitro abuse liability and off-target safety with human recombinant targets

• In vitro functional screen

Pharmacokinetics

• Pharmacokinetics
• Protein binding

Side effect profile

• Modified Irwin functional observational battery
• Rotarod

Pain models

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

Validated endpoints

• Cold allodynia behavior (acetone evaporation) test
• Dynamic weight bearing
• Facial mechanical allodynia behavior (von Frey filaments)
• Guarding behavior
• Mechanical allodynia behavior (von Frey filaments)

In vivo abuse liability

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