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linopirdine
- Development stage
- Discontinued
- Lead developer
- DuPont
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
Linopirdine is a synthetic small molecule belonging to the indole and pyridine chemical classes. It was developed as a putative cognition-enhancing agent, primarily investigated for the treatment of Alzheimer's disease. Linopirdine acts mainly by blocking neuronal M-type potassium currents (M-currents) mediated by KCNQ2/KCNQ3 (Kv7.2/Kv7.3) voltage-gated potassium channels, leading to increased acetylcholine release in the brain and enhanced neurotransmitter release including dopamine, serotonin (5-HT), GABA, and glutamate[1][2][3][4]. This mechanism was hypothesized to improve learning and memory function. Linopirdine also acts as an agonist of the TRPV1 channel at low concentrations, sensitizing these channels to heat[3]. Despite promising preclinical results, clinical trials in Alzheimer's disease did not demonstrate clinically meaningful cognitive improvement compared with placebo[6][8], leading to discontinuation of its development.
- Brand names
- Aviva
- Other names
- linopirine
02
Targets
Glycine receptorTRPV1 (Transient receptor potential cation channel subfamily V member 1)KCNQ1 (Potassium voltage-gated channel subfamily KQT member 1)KCNQ2 (Potassium voltage-gated channel subfamily KQT member 2)KCNQ4 (Potassium channel subfamily KQT member 4)
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