Reduction of haloperidol-induced side effects by ACP-103 in healthy volunteers

Background/Aims A novel serotonin 2A (5-HT2A) receptor inverse agonist, ACP-103, was tested to determine the potential of ACP-103 to inhibit central nervous system side effects produced by haloperidol. Methods Healthy male volunteers participated in a randomized, double blind, placebo-controlled, single dose crossover study. All subjects received a single dose of haloperidol (7.5 mg) in combination with either a single dose of placebo or a single dose of ACP-103 (100 mg). The washout period between treatment combinations was two weeks. Results Haloperidol caused measurable akathisia in 13 of 18 subjects and induced approximately a 3-fold increase in prolactin secretion. ACP-103 treatment caused a measurable and temporally consistent decrease in haloperidol-induced akathisia compared to placebo treated subjects as measured by the Barnes Akathisia Scale. ACP-103 significantly reduced haloperidol-induced hyperprolactinemia. The pharmacokinetics of haloperidol and ACP-103 were not affected by their co-administration. No serious adverse events were reported. Conclusions Data suggest that ACP-103, when co-administered with existing antipsychotic drugs, may reduce their side effects and expand their range of efficacy. ACP-103 is being developed as an adjunctive therapy for schizophrenia and as a therapy for treatment-induced dysfunction in Parkinson's disease. Clinical Pharmacology & Therapeutics (2005) 77, P98–P98; doi: 10.1016/j.clpt.2005.01.004