Tropisetron and its targets in Alzheimer's disease.
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.
Chiba University Center for Forensic Mental Health, Division of Clinical Neuroscience , 1-8-1 Inohana, Chiba 260-8670 , Japan +81 43 226 2517 ; +81 43 226 2561 ; hashimoto@faculty.chiba-u.jp.
Kenji
K
Hashimoto
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D006801:Humans; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000378:metabolism; D018722:Nicotinic Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D011812:Quinuclidines / Q000627:therapeutic use; D012702:Serotonin Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D013876:Thiophenes / Q000627:therapeutic use; D000077526:Tropisetron; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists*
C573817:7-chloro-N-quinuclidin-3-yl-benzo(b)thiophene-2-carboxamide; D007211:Indoles; D018722:Nicotinic Agonists; D011812:Quinuclidines; D012702:Serotonin Antagonists; D013876:Thiophenes; D064569:alpha7 Nicotinic Acetylcholine Receptor; D000077526:Tropisetron
5-hydroxytryptamine 3 receptor; Alzheimer’s disease; encenicline; inflammation; mild cognitive impairment; tropisetron; α7 nicotinic receptor; β-amyloid