N-Ethylnorketamine has anesthetic and analgesic effects with abuse liability

Arylcyclohexylamines is an ever-growing class of new psychoactive substances, including an increasing number of ketamine analogs. N-Ethylnorketamine (NENK) is a new synthetic ketamine analog that has emerged as an abused drug, but little is known about the pharmacological profile of NENK. In this study, we investigated the anesthetic and analgesic activity, abuse liability of NENK compared with ketamine. The ED₅₀ values of anesthetic activity for NENK and ketamine were 96.9, 69.4 mg/kg, respectively. The ED₅₀ values of analgesic activity for NENK and ketamine were 45.9 and 23.6 mg/kg, respectively. NENK induced significant conditioned place preference at a minimum dose of 10.0 mg/kg in mice, an effect comparable to that of ketamine (3.0 mg/kg). Acute injections of NENK or ketamine at 30.0 mg/kg enhanced locomotor activity, and repeated treatments with this dose induced locomotor sensitization after withdrawal. Taken together, these results clearly demonstrated that NENK has lower anesthetic and analgesic activity compared to ketamine, but has significant abuse liability.