PHA-543,613
Identifiers
  • N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.189.975 Edit this at Wikidata
Chemical and physical data
FormulaC15H17N3O2
Molar mass271.314 g·mol−1
3D model (JSmol)
  • C1CN2CCC1[C@H](C2)NC(=O)C3=NC=C4C(=C3)C=CO4
  • InChI=1S/C15H17N3O2/c19-15(12-7-11-3-6-20-14(11)8-16-12)17-13-9-18-4-1-10(13)2-5-18/h3,6-8,10,13H,1-2,4-5,9H2,(H,17,19)/t13-/m0/s1
  • Key:IPKZCLGGYKRDES-ZDUSSCGKSA-N
  (verify)

PHA-543,613 is a drug that acts as a potent and selective agonist for the α7 subtype of neural nicotinic acetylcholine receptors, with a high level of brain penetration and good oral bioavailability. It is under development as a possible treatment for cognitive deficits in schizophrenia.[1] It reduces excitotoxicity[2] and protects striatal dopaminergic neurons in rat models.[3] It also potentiates cognitive enhancement from memantine,[4][5] decreases dynorphin release[6] and inhibits GSK-B3.[7]

See also

References

  1. ^ Wishka DG, Walker DP, Yates KM, Reitz SC, Jia S, Myers JK, et al. (July 2006). "Discovery of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide, an agonist of the alpha7 nicotinic acetylcholine receptor, for the potential treatment of cognitive deficits in schizophrenia: synthesis and structure--activity relationship". Journal of Medicinal Chemistry. 49 (14): 4425–36. doi:10.1021/jm0602413. PMID 16821801.
  2. ^ Foucault-Fruchard L, Doméné A, Page G, Windsor M, Emond P, Rodrigues N, Dollé F, Damont A, Buron F, Routier S, Chalon S, Antier D (July 2017). "Neuroprotective effect of the alpha 7 nicotinic receptor agonist PHA 543613 in an in vivo excitotoxic adult rat model" (PDF). Neuroscience. 356: 52–63. doi:10.1016/j.neuroscience.2017.05.019. PMID 28527955.
  3. ^ Sérrière S, Doméné A, Vercouillie J, Mothes C, Bodard S, Rodrigues N, Guilloteau D, Routier S, Page G, Chalon S (2015). "Assessment of the Protection of Dopaminergic Neurons by an α7 Nicotinic Receptor Agonist, PHA 543613 Using [(18)F]LBT-999 in a Parkinson's Disease Rat Model". Frontiers in Medicine. 2: 61. doi:10.3389/fmed.2015.00061. PMC 4556971. PMID 26389120.
  4. ^ Bruszt N, Bali ZK, Tadepalli SA, Nagy LV, Hernádi I (August 2021). "Potentiation of cognitive enhancer effects of Alzheimer's disease medication memantine by alpha7 nicotinic acetylcholine receptor agonist PHA-543613 in the Morris water maze task". Psychopharmacology. doi:10.1007/s00213-021-05942-4. PMID 34387707.
  5. ^ Bali ZK, Bruszt N, Tadepalli SA, Csurgyók R, Nagy LV, Tompa M, Hernádi I (2019). "Cognitive Enhancer Effects of Low Memantine Doses Are Facilitated by an Alpha7 Nicotinic Acetylcholine Receptor Agonist in Scopolamine-Induced Amnesia in Rats". Frontiers in Pharmacology. 10: 73. doi:10.3389/fphar.2019.00073. PMC 6371842. PMID 30804787.
  6. ^ Ji L, Chen Y, Wei H, Feng H, Chang R, Yu D, Wang X, Gong X, Zhang M (July 2019). "Activation of alpha7 acetylcholine receptors reduces neuropathic pain by decreasing dynorphin A release from microglia". Brain Research. 1715: 57–65. doi:10.1016/j.brainres.2019.03.016. PMID 30898676.
  7. ^ Krafft PR, Altay O, Rolland WB, Duris K, Lekic T, Tang J, Zhang JH (March 2012). "α7 nicotinic acetylcholine receptor agonism confers neuroprotection through GSK-3β inhibition in a mouse model of intracerebral hemorrhage". Stroke. 43 (3): 844–50. doi:10.1161/STROKEAHA.111.639989. PMC 3293395. PMID 22207510.