linopirdine
Sign in to saveLinopirdine is a putative cognition-enhancing drug with a novel mechanism of action. Linopirdine blocks the KCNQ2\3 heteromer M current with an IC50 of 2.4 micromolar disinhibiting acetylcholine release, and increasing hippocampal CA3-schaffer collateral mediated glutamate release onto CA1 pyramidal neurons. In a murine model linopirdine is able to nearly completely reverse the senescence-related decline in cortical c-FOS, an effect which is blocked by atropine and MK-801, suggesting Linopirdine can compensate for the age related decline in acetylcholine release. Linopirdine also blocks homome
Research
254 papers- Linopirdine blocks alpha9alpha10-containing nicotinic cholinergic receptors of cochlear hair cells.Journal of the Association for Research in Otolaryngology : JARO · 2004
- The M-channel blocker linopirdine is an agonist of the capsaicin receptor TRPV1.Journal of pharmacological sciences · 2010
- A randomized, controlled trial of linopirdine in the treatment of Alzheimer's disease.The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques · 1997
- Pharmacology of the neurotransmitter release enhancer linopirdine (DuP 996), and insights into its mechanism of action.Advances in pharmacology (San Diego, Calif.) · 1996
- Linopirdine-supplemented resuscitation fluids reduce mortality in a model of ischemia-reperfusion injury induced acute respiratory distress syndrome.Physiological research · 2021
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Wikidata facts
- Mass
- 391.168
Show 3 more facts
- chemical formula
- C₂₆H₂₁N₃O
- canonical SMILES
- C1=CC=C(C=C1)N2C3=CC=CC=C3C(C2=O)(CC4=CC=NC=C4)CC5=CC=NC=C5
- Commons category
- Linopirdine
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Article
2 sectionsContents
- Synthesis
- References
Linopirdine is a putative cognition-enhancing drug with a novel mechanism of action. Linopirdine blocks the KCNQ2\3 heteromer M current with an IC50 of 2.4 micromolar disinhibiting acetylcholine release, and increasing hippocampal CA3-schaffer collateral mediated glutamate release onto CA1 pyramidal neurons. In a murine model linopirdine is able to nearly completely reverse the senescence-related decline in cortical c-FOS, an effect which is blocked by atropine and MK-801, suggesting Linopirdine can compensate for the age related decline in acetylcholine release. Linopirdine also blocks homomeric KCNQ1 and KCNQ4 voltage gated potassium channels which contribute to vascular tone with substantially less selectivity than KCNQ2/3. Linopirdine also acts as a glycine receptor antagonist in concentrations typical for Kv7 studies in the brain.
==Synthesis== left|thumb|701px|Linopirdine synthesis: ~90%: Patents ~90%: The amide formation between diphenylamine (1) and oxalyl chloride [79-37-8] gives intermediate, CID:11594101 (2). Haworth type intramolecular cyclization of the acid chloride occurs on heating to afford 1-phenylisatin [723-89-7] (3). The reaction with 4-picoline (4) under PTC with a Quat. salt afforded the carbinol, CID:10358387 (5). Dehydration of the alcohol using acetic anhydride gives [33546-08-6] (6). The reduction of the olefin then afforded the indolone, CID:10470081 (7). The 3 position is now activated by the adjacent benzene ring on one side and the carbonyl group on the other. Alkylation with 4-picolylchloride [10445-91-7] (8) proceeds with hydroxide as the base to afford Linopirdine (9).