Idalopirdine as a treatment for Alzheimer’s disease

Abstract

Introduction: Alzheimer’s disease (AD) is the most common cause of dementia in the elderly. Pharmacological treatment of AD involves acetylcholinesterase inhibitors (AChEIs) for mild-to-moderate AD and memantine for severe AD. These drugs provide mainly symptomatic short-term benefits without clearly counteracting the progression of the disease. Idalopirdine is an antagonist of the serotonin 6 (5-HT₆) receptor, which is expressed in areas of the CNS involved with memory. Given that there is evidence suggesting that the blockade of 5-HT₆ receptors induces acetylcholine release, it became reasonable to consider that 5-HT₆ antagonism could also be a promising approach for restoring acetylcholine levels in a deteriorated cholinergic system.

Areas covered: This review discusses the history leading to the discovery of idalopirdine, its pharmacokinetics and pharmacodynamics profile and safety issues, together with an overview of clinical trials carried out so far. A literature search was performed with PubMed using the keywords idalopirdine, AD and 5-HT₆ antagonists. The article is also based on information derived from the ClinicalTrials.gov site for clinical trials with idalopirdine.

Expert opinion: Idalopirdine is safe and well tolerated. It could be used as add-on therapy to potentiate the effect of available AChEIs in AD. Nevertheless, results from ongoing Phase III trials are needed to verify whether this drug has a significant clinical effect on cognition in association with AChEIs.

Keywords:

• Alzheimer’s disease
• antagonist
• clinical trial
• idalopirdine
• LuAE58054
• serotonin 6
• receptor

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents, received or pending, or royalties.