linopirdine

{{Short description|Chemical compound}}

{{Drugbox

| Verifiedfields = changed

| verifiedrevid = 462091934

| IUPAC_name = 1-phenyl-3,3-bis(pyridin-4-ylmethyl)-1,3-dihydro-2H-indol-2-one

| image = Linopirdine.svg

| tradename =

| pregnancy_AU =

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| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 105431-72-9

| ATC_prefix = N06

| ATC_suffix = BX09

| PubChem = 3932

| IUPHAR_ligand = 2599

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank =

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 3795

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = I5TB3NZ94T

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D04741

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 319111

| C=26 | H=21 | N=3 | O=1

| smiles = O=C2N(c1ccccc1C2(Cc3ccncc3)Cc4ccncc4)c5ccccc5

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C26H21N3O/c30-25-26(18-20-10-14-27-15-11-20,19-21-12-16-28-17-13-21)23-8-4-5-9-24(23)29(25)22-6-2-1-3-7-22/h1-17H,18-19H2

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = YEJCDKJIEMIWRQ-UHFFFAOYSA-N

}}

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{{cite journal | vauthors = Schnee ME, Brown BS | title = Selectivity of linopirdine (DuP 996), a neurotransmitter release enhancer, in blocking voltage-dependent and calcium-activated potassium currents in hippocampal neurons | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 286 | issue = 2 | pages = 709–717 | date = August 1998 | pmid = 9694925 }} disinhibiting acetylcholine release, and increasing hippocampal CA3-schaffer collateral mediated glutamate release onto CA1 pyramidal neurons.{{cite journal | vauthors = Sun J, Kapur J | title = M-type potassium channels modulate Schaffer collateral-CA1 glutamatergic synaptic transmission | journal = The Journal of Physiology | volume = 590 | issue = 16 | pages = 3953–3964 | date = August 2012 | pmid = 22674722 | pmc = 3476642 | doi = 10.1113/jphysiol.2012.235820 }} 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.{{cite journal | vauthors = Dent GW, Rule BL, Zhan Y, Grzanna R | title = The acetylcholine release enhancer linopirdine induces Fos in neocortex of aged rats | journal = Neurobiology of Aging | volume = 22 | issue = 3 | pages = 485–494 | year = 2001 | pmid = 11378256 | doi = 10.1016/s0197-4580(00)00252-9 | s2cid = 45164 }} 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.{{Cite journal | vauthors = Lu HW, Romero GE, Apostolides PF, Huang H, Trussell LO |date=2022-03-02 |title=Kv7 channel antagonists block glycine receptors | journal = bioRxiv |language=en |doi=10.1101/2022.03.02.482705|s2cid=247231429 }}