AR-R17779 hydrochloride

AR-R17779 hydrochloride is a potent and selective full agonist of nAChR, with Kis of 92 and 16000 nM for α7 and α4β2 subtype, respectively. AR-R17779 hydrochloride can improve learning and memory in rats. AR-R17779 hydrochloride also has anxiolytic activity. AR-R17779 hydrochloride can reduce inflammation by activating antiinflammatory cholinergic (vagal) pathways[1][2][4].

Signaling Pathways >> Membrane Transporter/Ion Channel >> nAChR

Signaling Pathways >> Neuronal Signaling >> nAChR

Research Areas >> Neurological Disease

IC50: 92 nM (α7-nAChR)[1]

AR-R17779 is 5-fold more potent and 35000-fold more selective than (-)-nicotine for the α7 nicotinic receptor[1]. AR-R17779 (200 nM; 24 h) inhibits the LPS-induced TNF production in macrophages[4].

AR-R17779 (1-5 mg/kg; i.p. twice a day for 7 d) ameliorates arthritis, reduces synovial inflammation, delays onset of disease and protects against joint destruction[3]. AR-R17779 (1-10 mg/kg; s.c. for 3 weeks) improves learning in two radial-arm maze tasks and reverses working memory impairment caused by fimbria-fornix sections in rats[2]. Animal Model: Male DBA/1 mice (8-10 weeks) were subjected to unilateral cervical vagotomy or sham surgery, after which arthritis was induced with type II collagen[3] Dosage: 1, 2.5, 5 mg/kg Administration: I.p. twice daily from day 20 until day 26 Result: Ameliorated arthritis and delayed onset of disease. Reduced erosive disease, cartilage degradation and synovial inflammation. Reduced TNFα levels in plasma and synovial tissue.

[1]. Mullen G, et, al. (-)-Spiro[1-azabicyclo[2.2.2]octane-3,5'-oxazolidin-2'-one], a conformationally restricted analogue of acetylcholine, is a highly selective full agonist at the alpha 7 nicotinic acetylcholine receptor. J Med Chem. 2000 Nov 2;43(22):4045-50.

[2]. Levin ED, et, al. AR-R17779, and alpha7 nicotinic agonist, improves learning and memory in rats. Behav Pharmacol. 1999 Nov;10(6-7):675-80.

[3]. Maanen MA, et, al. Stimulation of nicotinic acetylcholine receptors attenuates collagen-induced arthritis in mice. Arthritis Rheum. 2009 Jan;60(1):114-22.

[4]. Lopes F, et, al. Involvement of Mast Cells in α7 Nicotinic Receptor Agonist Exacerbation of Freund's Complete Adjuvant-Induced Monoarthritis in Mice.