The story of discovery of aripiprazole molecule?
Aripiprazole is an atypical antipsychotic medication that was discovered and developed by Otsuka Pharmaceutical Company, a Japanese pharmaceutical company, in the late 1980s and early 1990s.
The story of the discovery of the aripiprazole molecule began with the search for a new antipsychotic drug that would be effective in treating schizophrenia and other psychiatric disorders while minimizing the side effects associated with traditional antipsychotics, such as extrapyramidal symptoms and prolactin elevation.
The research team at Otsuka, led by Inji Tenmyo, focused on developing a compound that would act as a dopamine partial agonist, meaning it would modulate dopamine activity in the brain by acting as an agonist or an antagonist depending on the level of dopamine present.
After screening thousands of compounds, the team identified a promising lead compound, OPC-14597, which later became known as aripiprazole. Preclinical studies showed that aripiprazole exhibited a unique mechanism of action, acting as a partial agonist at dopamine D2 receptors and serotonin 5-HT1A receptors, while also having antagonistic effects at serotonin 5-HT2A receptors.
Clinical trials conducted in the 1990s demonstrated aripiprazole’s efficacy in treating schizophrenia and other psychiatric disorders, with a favorable side effect profile compared to traditional antipsychotics. Aripiprazole was found to be effective in reducing positive and negative symptoms of schizophrenia, with a lower risk of extrapyramidal symptoms, weight gain, and prolactin elevation.
In 2002, the U.S. Food and Drug Administration (FDA) approved aripiprazole for the treatment of schizophrenia, making it the first dopamine partial agonist antipsychotic available on the market. Since then, aripiprazole has been approved for additional indications, including bipolar disorder, major depressive disorder, and as an adjunctive treatment for depression.
The discovery of aripiprazole and its unique mechanism of action represented a significant advancement in the treatment of psychiatric disorders, offering a new therapeutic option with improved tolerability compared to older antipsychotic medications
