dextrorphan and Disease-Models--Animal

Interest in developing NMDA receptor antagonists with reduced side-effects for neurological and psychiatric disorders has been re-energized by the recent introduction of esketamine into clinical practice for treatment-resistant depression. Structural analogs of dextromethorphan bind with low affinity to the NMDA receptor ion channel, have functional effects in vivo, and generally display a lower propensity for side-effects than that of ketamine and other higher affinity antagonists. As such, the aim of the present study was to determine whether a series of N-substituted-3-alkoxy-substituted dextromethorphan analogs produce their anticonvulsant effects through NMDA receptor blockade. Compounds were studied against NMDA-induced seizures in rats. Compounds were administered intracerebroventricularly in order to mitigate confounds of drug metabolism that arise from systemic administration. Comparison of the anticonvulsant potencies to their affinities for NMDA, σ1, and σ2 binding sites were made in order to evaluate the contribution of these receptors to anticonvulsant efficacy. The potencies to block convulsions were positively associated with their affinities to bind to the NMDA receptor ion channel ([

Topics: Alcohols; Animals; Anticonvulsants; Binding Sites; Dextromethorphan; Dextrorphan; Disease Models, Animal; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Infusions, Intraventricular; Ligands; Male; N-Methylaspartate; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Receptors, sigma; Seizures; Sigma-1 Receptor; Treatment Outcome

Topics: Animals; Cardiopulmonary Bypass; Dextrorphan; Disease Models, Animal; Excitatory Amino Acids; Laminectomy; Sensitivity and Specificity; Spinal Cord Ischemia; Swine