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Chemical compound
PHA-543,613
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 InfoCard
100.189.975
Formula C 15 H 17 N 3 O 2
Molar mass 271.320 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
^ 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 .
^ 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 .
S2CID
4827887 .
^ 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 .
^ 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 . 238 (11): 3273–3281.
doi :
10.1007/s00213-021-05942-4 .
PMC
8605977 .
PMID
34387707 .
^ 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 .
^ 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 .
S2CID
81981843 .
^ 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 .
nAChRs Tooltip Nicotinic acetylcholine receptors
Agonists (and
PAMs Tooltip positive allosteric modulators )
5-HIAA
6-Chloronicotine
A-84,543
A-366,833
A-582,941
A-867,744
ABT-202
ABT-418
ABT-560
ABT-894
Acetylcholine
Altinicline
Anabasine
Anatabine
Anatoxin-a
AR-R17779
Bephenium hydroxynaphthoate
Butinoline
Butyrylcholine
Carbachol
Choline
Cotinine
Cytisine
Decamethonium
Desformylflustrabromine
Dianicline
Dimethylphenylpiperazinium
Epibatidine
Epiboxidine
Ethanol (alcohol)
Ethoxysebacylcholine
EVP-4473
EVP-6124
Galantamine
GTS-21
Ispronicline
Ivermectin
JNJ-39393406
Levamisole
Lobeline
MEM-63,908 (RG-3487)
Morantel
Nicotine (
tobacco )
NS-1738
PHA-543,613
PHA-709,829
PNU-120,596
PNU-282,987
Pozanicline
Pyrantel
Rivanicline
RJR-2429
Sazetidine A
SB-206553
Sebacylcholine
SIB-1508Y
SIB-1553A
SSR-180,711
Suberyldicholine
Suxamethonium (succinylcholine)
Suxethonium (succinyldicholine)
TC-1698
TC-1734
TC-1827
TC-2216
TC-5214
TC-5619
TC-6683
Tebanicline
Tribendimidine
Tropisetron
UB-165
Varenicline
WAY-317,538
XY-4083
Antagonists (and
NAMs Tooltip negative allosteric modulators )
Precursors (and
prodrugs )