Arecaidine propargyl ester (hydrobromide) (Synonyms: APE)

Arecaidine propargyl ester is an agonist of M₂ muscarinic acetylcholine receptors (mAChRs).¹ It selectively binds to M₂ over M₁, M₃, M₄, and M₅ mAChRs in CHO cells expressing the human receptors (K_is = 0.0871, 1.23, 0.851, 0.977, and 0.933 µM, respectively). Arecaidine propargyl ester induces contractions in isolated guinea pig atrium (pD₂ = 8.67). It induces apoptosis and the production of reactive oxygen species (ROS) in U87 and U251 glioblastoma cells when used at a concentration of 100 µM.² Arecaidine propargyl ester decreases mean arterial blood pressure in normotensive cats (ED₂₅ = 1.9 nmol/kg).³ It is toxic to house flies (Musca) when administered at a dose of 75 µg/fly.⁴

1.Scapecchi, S., Matucci, R., Bellucci, C., et al.Highly chiral muscarinic ligands: the discovery of (2S,2’R,3’S,5’R)-1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine 3-sulfoxide methyl iodide, a potent, functionally selective, M2 partial agonistJ. Med. Chem.49(6)1925-1931(2006) 2.Di Bari, M., Tombolillo, B., Conte, C., et al.Cytotoxic and genotoxic effects mediated by M2 muscarinic receptor activation in human glioblastoma cellsNeurochem. Int.90261-270(2015) 3.Porsius, A.J., and Van Zwieten, P.A.Central action of some cholinergic drugs (arecaidine esters) and nicotine on blood pressure and heart rate of catsProg. Brain Res.47131-135(1977) 4.Honda, H., Tomizawa, M., and Casida, J.E.Insect muscarinic acetylcholine receptor: Pharmacological and toxicological profiles of antagonists and agonistsJ. Agric. Food Chem.55(6)2276-2281(2007)