Update on the development of lurasidone as a treatment for patients with acute schizophrenia Full Text
Drug Design, Development and Therapy, 05/23/2012
Yasui–Furukori N – Lurasidone treatment produced improvements in Montgomery–Asberg Depression Rating Scale scores at 6 weeks that were significantly greater than placebo.
- Lurasidone is a novel benzisothiazole antipsychotic drug for the treatment of schizophrenia.
- Of the antipsychotic drugs, lurasidone has the highest affinity for the 5-hydroxytryptamine (5-HT)7 receptor.
- Lurasidone also has high affinities for the dopamine D2, 5HT2A, 5-HT1A and α2C adrenergic receptors.
- Moreover, lurasidone has low affinities for the α1 adrenergic, histamine H1 and muscarinic M1 receptors.
- The involvement of 5-HT7 receptors in cognitive processes has been suggested by both pharmacological and molecular investigations.
- Chronic treatment with lurasidone increases neurotrophin BDNF mRNA levels in both the hippocampus (ventral and dorsal) and prefrontal cortex under basal conditions or in response to an acute swim stress.
- Lurasidone may potentiate N-methyl-D-aspartate receptor (NMDAR) function through antagonistic action on 5-HT7 receptors without a direct affinity for NMDARs.
- These results suggest that lurasidone treatment may be a novel approach for the prevention of the development of cognitive impairment in individuals who are at risk for schizophrenia or related disorders involving cognitive impairment.
- In clinical trials, treatment with lurasidone was associated with significantly greater endpoint improvement versus placebo on the Positive and Negative Syndrome Scale total score after 6 weeks among subjects receiving 80 or 160 mg.
- The most frequent side effects of lurasidone were akathisia, nausea, parkinsonism, dizziness and somnolence.
- Once-daily treatment with lurasidone at 160 mg was superior to placebo based on the composite cognitive functioning measure.