title: Idalopirdine as a treatment for Alzheimer's disease.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico , Milan , Italy +390255033847 ; +390255036580 ; daniela.galimberti@unimi.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D001596:Benzylamines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007211:Indoles / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011985:Receptors, Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D005466:Fluorocarbons
chemical_list: D001596:Benzylamines; D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C568612:(2-(6-fluoro-1H-indol-3-yl)-ethyl)-(3-(2,2,3,3-tetrafluoropropoxy)benzyl)amine; D005466:Fluorocarbons; C097216:serotonin 6 receptor
keywords: Alzheimer’s disease; LuAE58054; antagonist; clinical trial; idalopirdine; receptor; serotonin 6