Lurasidone is a new atypical
antipsychotic in the benzoisothiazoles class of chemicals. Like most second-generation
antipsychotics it is a full antagonist at
dopamine D(2) and
serotonin 5-HT(2A) receptors, and is a partial agonist at 5-HT(1A) receptors, a property shared by some but not all older agents. It has much greater affinity for 5-HT(7) subtype receptors than other atypical
antipsychotics. Pharmacokinetic studies showed that
lurasidone is reasonably rapidly absorbed, with bioavailability appearing to be increased by food.
Lurasidone undergoes extensive metabolism to a number of metabolites, some of which retain pharmacological activities. Metabolism is mainly by
CYP3A4, resulting in steady-state concentrations that vary between individuals and are potentially affected by strong inducers and inhibitors of this
enzyme. Short-term clinical trials have demonstrated the efficacy of
lurasidone in acute
schizophrenia, with doses of 40 and 80 mg/day giving significant improvements from baseline in the PANSS and BPRS scores. The most common adverse events are
nausea,
vomiting,
akathisia,
dizziness, and sedation, with minimal increases in the risk of developing
metabolic syndrome.
Lurasidone did not raise the risk of QTc interval prolongation, although additional studies are required. Long-term trials are also needed to assess the risk of new-onset diabetes. Ongoing trials in patients with
bipolar disorder are being completed but, again, efficacy and safety have been investigated only in a few short-term clinical trials.