Tropisetron and its targets in Alzheimer's disease.

Expert opinion on therapeutic targets

PubMedID: 25399811

Hashimoto K. Tropisetron and its targets in Alzheimer's disease. Expert Opin Ther Targets. 2014;1-5.
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-ß peptides (Aß) and the a7 nicotinic acetylcholine receptor (a7 nAChR) plays a key role in AD pathology, and that a7 nAChR agonists could act as potential therapeutic drugs for AD. A recent study demonstrated that tropisetron, a potent a7 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 Aß deposition and inflammation in the brains of subjects with amnestic mild cognitive impairment (MCI) before the onset of AD. Given the role of a7 nAChR in Aß 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.