Evaluation of samidorphan, a μ-opioid antagonist, in a drug discrimination assay in rats.

Unlabelled: Preclinical Research & Development Background: Samidorphan, a μ-opioid receptor antagonist, is in clinical development for central nervous system related diseases. The discriminative stimulus effects of samidorphan were assessed in rats trained to discriminate the effects of a known morphinan of abuse, morphine, from that of saline.

Methods: Escalating doses of samidorphan were substituted for morphine and rats were allowed to respond on two levers for food reward.

Improvements in self-administration studies based on changes in skin button type and surgical technique.

Introduction: These studies, ranging in duration from 3 to 8months, evaluated the patency and longevity of the intravenous (IV) self-administration surgical model in male Sprague Dawley rats. Surgeries were categorized and assessed based on the number of catheter and/or skin button repairs required per animal across four separate self-administration studies. Design improvements in skin button types and changes in surgical procedures were chronologically tracked and assessed.

Withdrawal assessment following subchronic oral ketamine administration in Cynomolgus macaques.

Recently there is increased regulatory interest in the assessment of physical dependence and withdrawal as part of the safety assessment for novel therapeutic entities. Choosing appropriate and sensitive parameters to detect withdrawal syndromes, and relevant positive control comparator drugs that can be administered in the same manner as the test agent, are critical study design elements. Pilot studies to determine the effects of oral ketamine in cynomolgus monkeys during, and following cessation of treatment, were explored.