Galimberti_2015_Expert.Opin.Investig.Drugs_24_981

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.