:PHA-543,613

{{Short description|Chemical compound}}

{{Drugbox

| verifiedrevid = 425002498

| IUPAC_name = N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide

| image = PHA-543,613.svg

| width = 240

| tradename =

| legal_status =

| routes_of_administration =

| IUPHAR_ligand = 3998

| CAS_number = 478149-53-0

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

| UNII = R36R9KVD6Y

| ATC_suffix =

| PubChem = 11493927

| ChEMBL = 214268

| ChemSpiderID = 8105752

| C=15 | H=17 | N=3 | O=2

| smiles = C1CN2CCC1[C@H](C2)NC(=O)C3=NC=C4C(=C3)C=CO4

| StdInChI = 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

| StdInChIKey = IPKZCLGGYKRDES-ZDUSSCGKSA-N

}}

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.{{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 }} It reduces excitotoxicity{{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 |s2cid=4827887 |url=https://zenodo.org/record/1045803 |issn=}} and protects striatal dopaminergic neurons in rat models.{{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=|doi-access=free }} It also potentiates cognitive enhancement from memantine,{{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= 238|issue= 11|pages= 3273–3281|date=August 2021 |pmid=34387707 |doi=10.1007/s00213-021-05942-4 |pmc=8605977 |url= |issn=|doi-access=free }}{{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=|doi-access=free }} decreases dynorphin release{{cite journal |vauthors=Ji L, Chen Y, Wei H, Feng H, Chang R, Yu D, Wang X, Gong X, Zhang M |title=Activation of alpha7 acetylcholine receptors reduces neuropathic pain by decreasing dynorphin A release from microglia |journal=Brain Research |volume=1715 |issue= |pages=57–65 |date=July 2019 |pmid=30898676 |doi=10.1016/j.brainres.2019.03.016 |s2cid=81981843 |url= |issn=}} and inhibits GSK-B3.{{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=}}