Acadia Pharmaceuticals Inc, a biopharmaceutical company, reported results from a clinical study that assessed the ability of ACP-103, Acadia's proprietary 5-HT2A inverse agonist, to reduce the side effects associated with antipsychotic drug treatment with haloperidol. Results of the clinical study showed that ACP-103 reduced both the motor disturbances and hyperprolactinemia, a condition of elevated prolactin secretion, caused by haloperidol treatment.

According to a company release, the double-blind, placebo-controlled clinical study, conducted in Sweden, involved 18 healthy volunteers. All subjects were administered a single 7.5 mg dose of haloperidol and 11 of these subjects developed measurable akathisia. In addition, the haloperidol treatment induced about a three-fold increase in prolactin secretion.

Results of the study indicated that a single treatment with ACP-103 reduced akathisia symptoms in most subjects and, importantly, that four of the subjects had complete disappearance of haloperidol-induced akathisia as measured on the Barnes Subjective-Distress Rating Scale.

Researchers observed that maximal reductions appeared at the time of peak plasma levels of ACP-103 following a single 100 mg dose that produced plasma levels approximately equivalent to those achieved at steady state following chronic once daily administration of a 20 mg dose of ACP-103. In addition, ACP-103 reduced haloperidol-induced increases in prolactin secretion by 33 per cent. This reduction is highly statistically significant (p<0.001, paired t-test). The pharmacokinetics of haloperidol and ACP-103 were not affected by their co-administration, indicating a lack of drug-drug interactions between these two drugs. No serious adverse events were reported in this study.

Acadia is developing ACP-103 as a novel therapy for schizophrenia to be used in combination with currently available antipsychotic drugs including haloperidol, Zyprexa, Risperdal and Seroquel. These antipsychotics cause a variety of unfavourable side effects, including hyperprolactinemia, which can adversely affect menstrual and sexual function, and akathisia, an extremely distressful motor disturbance characterized by feelings of inner restlessness and an urge to move. ACP-103, when combined with existing antipsychotic drugs, may reduce the side effects associated with these drugs and expand their range of efficacy.

"We are delighted that the results of this clinical study suggest that the adjunctive use of ACP-103 has the ability to reduce the side effects associated with antipsychotic drug treatment," Mark R Brann, Acadia's president and CSO said adding, "This is the first of a series of studies in our Phase II program that will examine the ability of ACP-103 to work in combination with existing antipsychotic drugs for more optimal drug therapy. ACADIA has discovered that most antipsychotic drugs, including haloperidol and the market leaders Zyprexa, Risperdal and Seroquel, lack sufficient activity at 5-HT2A receptors. By adding ACP-103 on top of these antipsychotic drugs, we believe that one can optimize activity at 5-HT2A receptors relative to activity at D2 receptors to improve the efficacy and reduce the side effects of this important class of drugs."

Akathisia and hyperprolactinemia are troubling side effects of most existing antipyschotic drugs. Akathisia can lead to high levels of discomfort and ultimately is a major contributor to patient noncompliance. Patients with schizophrenia displaying hyperprolactinemia may be at high risk of developing osteoporosis and other side effects including decreased libido and the development of breast tissue in men.