N-allylnormetazocine (NANM) disrupts prepulse inhibition (PPI) of acoustic startle in mice, a measure of sensorimotor gating. Racemic NANM and its (+)-isomer produced dose-dependent PPI disruption (3-30 mg/kg), while the (-)-isomer had no effect. Blocking kappa opioid or sigma-1 receptors did not prevent this disruption, and a selective kappa agonist also had no effect on PPI. The findings indicate that NANM's effects on sensorimotor gating are mediated through the PCP site of the NMDA receptor, not through kappa or sigma-1 receptors, consistent with evidence that sigma-1 receptors are not linked to hallucinogenic or psychotomimetic effects.
Methoxetamine (MXE), a ketamine analog sold online, produces behavioral effects in rats that closely resemble those of other dissociative anesthetics like phencyclidine (PCP) and ketamine. In Sprague-Dawley rats, MXE disrupted prepulse inhibition (PPI) of acoustic startle at doses of 3 and 10 mg/kg, with a potency ranking (PCP > MXE > S-(+)-ketamine > NANM > R-(-)-ketamine) that matches their affinities for the PCP binding site on NMDA receptors. In the behavioral pattern monitor, 10 mg/kg MXE caused locomotor hyperactivity, reduced rearing, increased path roughness, and perseverative locomotion—effects similar to those of PCP. These findings indicate MXE acts as a dissociative drug with abuse potential comparable to PCP and ketamine.