INTERACTION OF EBEINONE, AN ALKALOID FROM FRITILLARIA-IMPERIALIS, AT 2 MUSCARINIC ACETYLCHOLINE-RECEPTOR SUBTYPES

The ability of the alkaloid, ebeinone, isolated from Fritillaria imper ialis, to act at muscarinic M(2) and M(3) acetylcholine receptors was investigated. In functional studies with guinea-pig left atrium, ebein one was found to be ca. 10-fold more active as an antagonist of respon ses to carbachol (CCh) than in either guinea-pig ileum or trachea. Est imates of dissociation constants (K-B values) in the three tissues wer e 77.3, 931.1 and 547.0 nM, respectively. Inhibition binding studies i n rat atria with the non-selective antagonist [H-3]N-methylscopolamine ([H-3]NMS) showed ebeinone to have a K-I value of 80.9 nM. Comparison of ebeinone with pancuronium, another steroid-like compound with a si milar K-B value at the muscarinic M(2) receptor, found both compounds able to retard the dissociation rate of [H-3]NMS in atria, indicating an allosteric mode of interaction at the M(2) receptor. It is conclude d that ebeinone exhibited a higher affinity for muscarinic M(2) recept ors than for M(3) receptors in the guinea-pig and that it interacted a llosterically at rat atrial M(2) receptors.