PHA-543,613 explained

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

• Nefiracetam

Notes and References

1. 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 . 6 . 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 . July 2006 . 16821801 . 10.1021/jm0602413 .
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 . Neuroprotective effect of the alpha 7 nicotinic receptor agonist PHA 543613 in an in vivo excitotoxic adult rat model . . 356 . 52–63 . July 2017 . 28527955 . 10.1016/j.neuroscience.2017.05.019 . 4827887 .
3. Sérrière S, Doméné A, Vercouillie J, Mothes C, Bodard S, Rodrigues N, Guilloteau D, Routier S, Page G, Chalon S . 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 . . 2 . 61 . 2015 . 26389120 . 4556971 . 10.3389/fmed.2015.00061 . free .
4. Bruszt N, Bali ZK, Tadepalli SA, Nagy LV, Hernádi I . 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 . . 238. 11. 3273–3281. August 2021 . 34387707 . 10.1007/s00213-021-05942-4 . 8605977 . free .
5. Bali ZK, Bruszt N, Tadepalli SA, Csurgyók R, Nagy LV, Tompa M, Hernádi I . Cognitive Enhancer Effects of Low Memantine Doses Are Facilitated by an Alpha7 Nicotinic Acetylcholine Receptor Agonist in Scopolamine-Induced Amnesia in Rats . . 10 . 73 . 2019 . 30804787 . 6371842 . 10.3389/fphar.2019.00073 . free .
6. Ji L, Chen Y, Wei H, Feng H, Chang R, Yu D, Wang X, Gong X, Zhang M . Activation of alpha7 acetylcholine receptors reduces neuropathic pain by decreasing dynorphin A release from microglia . . 1715 . 57–65 . July 2019 . 30898676 . 10.1016/j.brainres.2019.03.016 . 81981843 .
7. Krafft PR, Altay O, Rolland WB, Duris K, Lekic T, Tang J, Zhang JH . α7 nicotinic acetylcholine receptor agonism confers neuroprotection through GSK-3β inhibition in a mouse model of intracerebral hemorrhage . . 43 . 3 . 844–50 . March 2012 . 22207510 . 3293395 . 10.1161/STROKEAHA.111.639989 .