Tropisetron and its targets in Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder. Despite this, there are no drugs for preventing the onset of AD. Preclinical studies suggest that the interaction between amyloid-β peptides (Aβ) and the α7 nicotinic acetylcholine receptor (α7 nAChR) plays a key role in AD pathology, and that α7 nAChR agonists could act as potential therapeutic drugs for AD. A recent study demonstrated that tropisetron, a potent α7 nAChR agonist and serotonin 5-hydroxytryptamine₃ receptor antagonist, also bound to the ectodomain of amyloid precursor protein. Furthermore, tropisetron promoted greater improvements in memory than current AD therapeutic drugs, such as memantine and donepezil. Positron emission tomography studies detected Aβ deposition and inflammation in the brains of subjects with amnestic mild cognitive impairment (MCI) before the onset of AD. Given the role of α7 nAChR in Aβ deposition and inflammation, tropisetron represents an attractive potential therapeutic drug to delay or prevent MCI and AD. Additionally as this drug is used internationally to treat chemotherapy-induced emesis, its safety record is already known.

Keywords:

• 5-hydroxytryptamine 3 receptor
• Alzheimer’s disease
• encenicline
• inflammation
• mild cognitive impairment
• tropisetron
• α7 nicotinic receptor
• β-amyloid

Declaration of interest

The study was supported by a Grant-in-Aid from the Minister of Education, Culture, Sports, Science, and Technology of Japan. K Hashimoto holds a patent for the use of tropisetron in neuropsychiatric diseases, including schizophrenia and Alzheimer’s disease. In addition, K Hashimoto has served as a scientific consultant to Astellas, Dainippon-Sumitomo and Taisho, and he has also received research support from Abbvie, Dainippon-Sumitomo, Otsuka, and Taisho. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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