Sazetidine A Explained

Sazetidine A (AMOP-H-OH) is a drug which acts as a subtype selective partial agonist at α4β2 neural nicotinic acetylcholine receptors, acting as an agonist at (α4)2(β2)3 pentamers, but as an antagonist at (α4)3(β2)2 pentamers.^{[1] [2]} It has potent analgesic effects in animal studies comparable to those of epibatidine, but with less toxicity,^[3] and also has antidepressant action.^[4]

Notes and References

1. Xiao Y, Fan H, Musachio JL, Wei ZL, Chellappan SK, Kozikowski AP, Kellar KJ . Sazetidine-A, a novel ligand that desensitizes alpha4beta2 nicotinic acetylcholine receptors without activating them . Molecular Pharmacology . 70 . 4 . 1454–60 . October 2006 . 16857741 . 10.1124/mol.106.027318 . 6599272 .
2. Zwart R, Carbone AL, Moroni M, Bermudez I, Mogg AJ, Folly EA, Broad LM, Williams AC, Zhang D, Ding C, Heinz BA, Sher E . 6 . Sazetidine-A is a potent and selective agonist at native and recombinant alpha 4 beta 2 nicotinic acetylcholine receptors . Molecular Pharmacology . 73 . 6 . 1838–43 . June 2008 . 18367540 . 10.1124/mol.108.045104 . 24632914 .
3. Cucchiaro G, Xiao Y, Gonzalez-Sulser A, Kellar KJ . Analgesic effects of Sazetidine-A, a new nicotinic cholinergic drug . Anesthesiology . 109 . 3 . 512–9 . September 2008 . 18719450 . 10.1097/ALN.0b013e3181834490 . 22185882 . free .
4. Kozikowski AP, Eaton JB, Bajjuri KM, Chellappan SK, Chen Y, Karadi S, He R, Caldarone B, Manzano M, Yuen PW, Lukas RJ . 6 . Chemistry and pharmacology of nicotinic ligands based on 6-[5-(azetidin-2-ylmethoxy)pyridin-3-yl]hex-5-yn-1-ol (AMOP-H-OH) for possible use in depression . ChemMedChem . 4 . 8 . 1279–91 . August 2009 . 19569163 . 2955514 . 10.1002/cmdc.200900079 .