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'''PHA-543,613''' is a drug that acts as a potent and selective [[agonist]] for the [[Alpha-7 nicotinic receptor|α7]] subtype of neural [[nicotinic acetylcholine receptor]]s, with a high level of brain penetration and good oral bioavailability. It is under development as a possible treatment for cognitive deficits in [[schizophrenia]].<ref>{{cite journal | vauthors = Wishka DG, Walker DP, Yates KM, Reitz SC, Jia S, Myers JK, Olson KL, Jacobsen EJ, Wolfe ML, Groppi VE, Hanchar AJ, Thornburgh BA, Cortes-Burgos LA, Wong EH, Staton BA, Raub TJ, Higdon NR, Wall TM, Hurst RS, Walters RR, Hoffmann WE, Hajos M, Franklin S, Carey G, Gold LH, Cook KK, Sands SB, Zhao SX, Soglia JR, Kalgutkar AS, Arneric SP, Rogers BN | display-authors = 6 | title = 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 = Journal of Medicinal Chemistry | volume = 49 | issue = 14 | pages = 4425–36 | date = July 2006 | pmid = 16821801 | doi = 10.1021/jm0602413 }}</ref>
'''PHA-543,613''' is a drug that acts as a potent and selective [[agonist]] for the [[Alpha-7 nicotinic receptor|α7]] subtype of neural [[nicotinic acetylcholine receptor]]s, with a high level of brain penetration and good oral bioavailability. It is under development as a possible treatment for cognitive deficits in [[schizophrenia]].<ref>{{cite journal | vauthors = Wishka DG, Walker DP, Yates KM, Reitz SC, Jia S, Myers JK, Olson KL, Jacobsen EJ, Wolfe ML, Groppi VE, Hanchar AJ, Thornburgh BA, Cortes-Burgos LA, Wong EH, Staton BA, Raub TJ, Higdon NR, Wall TM, Hurst RS, Walters RR, Hoffmann WE, Hajos M, Franklin S, Carey G, Gold LH, Cook KK, Sands SB, Zhao SX, Soglia JR, Kalgutkar AS, Arneric SP, Rogers BN | display-authors = 6 | title = 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 = Journal of Medicinal Chemistry | volume = 49 | issue = 14 | pages = 4425–36 | date = July 2006 | pmid = 16821801 | doi = 10.1021/jm0602413 }}</ref> It reduces excitotoxicity and protects striatal dopaminergic neurons in rat models.<ref name="pmid28527955">{{cite journal |vauthors=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 |title=Neuroprotective effect of the alpha 7 nicotinic receptor agonist PHA 543613 in an in vivo excitotoxic adult rat model |journal=[[Neuroscience]] |volume=356 |issue= |pages=52–63 |date=July 2017 |pmid=28527955 |doi=10.1016/j.neuroscience.2017.05.019 |url= |issn=}}</ref><ref name="pmid26389120">{{cite journal |vauthors=Sérrière S, Doméné A, Vercouillie J, Mothes C, Bodard S, Rodrigues N, Guilloteau D, Routier S, Page G, Chalon S |title=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 |journal=[[Frontiers in Medicine]] |volume=2 |issue= |pages=61 |date=2015 |pmid=26389120 |pmc=4556971 |doi=10.3389/fmed.2015.00061 |url= |issn=}}</ref> It also potentiates cognitive enhacement from memantine and inhibits GSK-B3.<ref name="pmid22207510">{{cite journal |vauthors=Krafft PR, Altay O, Rolland WB, Duris K, Lekic T, Tang J, Zhang JH |title=α7 nicotinic acetylcholine receptor agonism confers neuroprotection through GSK-3β inhibition in a mouse model of intracerebral hemorrhage |journal=[[Stroke]] |volume=43 |issue=3 |pages=844–50 |date=March 2012 |pmid=22207510 |pmc=3293395 |doi=10.1161/STROKEAHA.111.639989 |url= |issn=}}</ref><ref name="pmid34387707">{{cite journal |vauthors=Bruszt N, Bali ZK, Tadepalli SA, Nagy LV, Hernádi I |title=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 |journal=[[Psychopharmacology]] |volume= |issue= |pages= |date=August 2021 |pmid=34387707 |doi=10.1007/s00213-021-05942-4 |url= |issn=}}</ref><ref name="pmid30804787">{{cite journal |vauthors=Bali ZK, Bruszt N, Tadepalli SA, Csurgyók R, Nagy LV, Tompa M, Hernádi I |title=Cognitive Enhancer Effects of Low Memantine Doses Are Facilitated by an Alpha7 Nicotinic Acetylcholine Receptor Agonist in Scopolamine-Induced Amnesia in Rats |journal=[[Frontiers in Pharmacology]] |volume=10 |issue= |pages=73 |date=2019 |pmid=30804787 |pmc=6371842 |doi=10.3389/fphar.2019.00073 |url= |issn=}}</ref>


== See also ==
== See also ==

Revision as of 08:35, 22 August 2021

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 and protects striatal dopaminergic neurons in rat models.[2][3] It also potentiates cognitive enhacement from memantine and inhibits GSK-B3.[4][5][6]

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". 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  4. ^ 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.
  5. ^ 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.
  6. ^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
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