Linopirdine

Linopirdine

Linopirdine
Systematic (IUPAC) name
1-phenyl-3,3-bis(pyridin-4-ylmethyl)-1,3-dihydro-2H-indol-2-one
Clinical data
Legal status
?
Identifiers
CAS number  N
ATC code N06
PubChem
IUPHAR ligand
ChemSpider  YesY
UNII  YesY
KEGG  YesY
ChEMBL  YesY
Chemical data
Formula C26H21N3O 
Mol. mass 391.465 g/mol
 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 2.4nM[1] disinhibiting acetylcholine release, and increasing hippocampal CA3-schaffer collateral mediated glutamate release onto CA1 pyramidal neurons.[2] 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.[3] Linopirdine also blocks homomeric KCNQ1 and KCNQ4 voltage gated potassium channels which contribute to vascular tone with substantially less selectivity than KCNQ2/3.[1]

Synthesis

Linopirdine synthesis:[4]

See also

References

  1. ^ a b Schnee, M. E.; Brown, B. S. (1998). "Selectivity of linopirdine (DuP 996), a neurotransmitter release enhancer, in blocking voltage-dependent and calcium-activated potassium currents in hippocampal neurons". The Journal of pharmacology and experimental therapeutics 286 (2): 709–717.  
  2. ^ Sun, J.; Kapur, J. (2012). "M-type potassium channels modulate Schaffer collateral-CA1 glutamatergic synaptic transmission". The Journal of Physiology 590 (16): 3953–3964.  
  3. ^ Dent, G. W.; Rule, B. L.; Zhan, Y.; Grzanna, R. (2001). "The acetylcholine release enhancer linopirdine induces Fos in neocortex of aged rats". Neurobiology of aging 22 (3): 485–494.  
  4. ^ Bryant, W. M.; Huhn, G. F.; Jensen, J. H.; Pierce, M. E.; Stammbach, C. (1993). "A Large Scale Preparation of the Cognitive Enhancer Linopirdine". Synthetic Communications 23 (11): 1617.