Stereochemical considerations in relation to the pharmacological activity of Pterotaberna alkaloids

Five 2-acylindole alkaloids, isolated from the leaves of Pterotaberna inconspicua, were pharmacologically investigated. The major alkaloids methuenine and 16-epimethuenine showed some interesting pharmacological features, whereas the minor alkaloids including 6-oxomethuenine and methuenine N-oxide were almost devoid of these pharmacological properties. Methuenine, being the most potent, was characterized as a non competitive antagonist against acetylcholine (pD'2=5.10 +/- 0.11) and histamine (pD'2 = 5.13 +/- 0.14) in guinea-pig ileum. Its potency was comparable to that of papaverine. 16-Epimethuenine behaved as a weak antihistaminic (pA2 = 6.55 +/- 0.08). The stereochemistry of both components is discussed in relation to their pharmacological activity.