Our lead investigational drug candidate intepirdine is in Phase 3 development for the treatment of patients with mild to moderate Alzheimer's disease who are also taking donepezil.*
Intepirdine is an orally administered, potent antagonist of the 5HT6 receptor. This receptor is expressed almost exclusively within the central nervous system, and blocking the 5HT6 receptor promotes the release of acetylcholine in the brain.i Patients with Alzheimer's disease have deficits in brain levels of this critical neurotransmitter, which is believed to be responsible for alertness, memory, thought, and judgment—key components of cognition and function that are impaired in Alzheimer's disease.ii
Mechanism of Action of Intepiridine With Cholinesterase Inhibitors
When 5HT6 receptor antagonists are used together with cholinesterase inhibitors, they increase the concentration of acetylcholine through a complementary mechanism without worsening the side effects commonly associated with cholinesterase inhibitors, such as nausea and vomiting.iii
Intepirdine directly increases the concentration of acetylcholine by promoting its release within the brain. Donepezil also increases acetylcholine, but does so nonselectively and indirectly by preventing its breakdown. In combination, intepirdine and donepezil work together to amplify acetylcholine levels in the brain.iii
* Intepirdine is not yet approved for any indication in any market.
- Ramirez MJ. 5-HT6 receptors and Alzheimer's disease. Alzheimer Res Ther. 2013;5(2):15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3706851/. Published April 22, 2013. Accessed August 16, 2017.
- English BA, Jones CK. Cholinergic neurotransmission. In: Robertson D, et al, eds. Primer on the Autonomic Nervous System. 3rd ed. San Diego, CA: Elsevier; 2012:71-74.
- Maher-Edwards G, Dixon R, Hunter J, et al. SB-742457 and donepezil in Alzheimer disease: a randomized, placebo-controlled study. Int J Geriatr Psychiatry. 2011;26(5):536-544.