Journal of clinical psychopharmacology
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J Clin Psychopharmacol · Aug 2012
Randomized Controlled TrialA Randomized, placebo-controlled, crossover pilot trial of the oral selective NR2B antagonist MK-0657 in patients with treatment-resistant major depressive disorder.
Converging lines of evidence suggest that the glutamatergic system may play an increasingly important role in the development of novel therapeutics for major depressive disorder (MDD), particularly agents associated with rapid antidepressant effects. Diverse glutamatergic modulators targeting N-methyl-D-aspartate receptors have shown efficacy in MDD, but their associated psychotomimetic effects presently preclude their use in larger samples. This small, randomized, double-blind, placebo-controlled, crossover pilot study evaluated the potential antidepressant efficacy and tolerability of an oral formulation of the selective N-methyl-D-aspartate NR2B antagonist MK-0657 in patients with treatment-resistant MDD (TRD). ⋯ No serious or dissociative adverse effects were observed in patients receiving this oral formulation of MK-0657. Despite the small sample size, this pilot study suggests that an oral formulation of the NR2B antagonist MK-0657 may have antidepressant properties in TRD patients. Further studies with larger sample sizes are necessary to confirm these preliminary findings.
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J Clin Psychopharmacol · Aug 2012
Randomized Controlled TrialHuman abuse potential and cognitive effects of taranabant, a cannabinoid 1 receptor inverse agonist: a randomized, double-blind, placebo- and active-controlled, crossover study in recreational polydrug users.
Taranabant is a cannabinoid 1 receptor inverse agonist that was in development for treatment of obesity. Because of central nervous system effects, the study was performed to assess the abuse potential and cognitive effects of taranabant in recreational polydrug users compared with phentermine, dronabinol, and placebo. ⋯ The phentermine and dronabinol results demonstrate the validity and sensitivity of the study. Taranabant did not consistently show stimulant/cannabis-like effects or abuse potential in recreational polydrug users, indicating that cannabinoid 1 receptor inverse agonists/antagonists are unlikely to be recreationally abused.