Journal of clinical psychopharmacology
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J Clin Psychopharmacol · Apr 2011
Randomized Controlled Trial Multicenter Study Comparative Study Controlled Clinical TrialA double-blind, randomized, placebo-controlled study of the dopamine D₃ receptor antagonist ABT-925 in patients with acute schizophrenia.
There is substantial preclinical and clinical evidence to suggest a potential role for the dopamine D₃ receptor in the treatment of schizophrenia. ABT-925 is a selective dopamine D₃ receptor antagonist with an approximately 100-fold higher in vitro affinity for dopamine D₃ versus D₂ receptors. This double-blind, randomized, placebo-controlled, escalating-dose, parallel-group study assessed the efficacy and safety of ABT-925 in the treatment of patients with acute exacerbation of schizophrenia. ⋯ Pharmacokinetic parameter estimates increased with dose in a linear fashion. ABT-925 50 mg QD and 150 mg QD were generally well tolerated, with adverse event profiles similar to that of placebo. Findings from a concurrent positron emission tomography study among healthy volunteers suggest that the ABT-925 doses used in this study may not have been sufficient to adequately occupy D₃ receptors, thereby underscoring the importance of pharmacodynamic markers, such as PET, in determining appropriate compound doses before embarking on studies in a target population.