Synthesis of poison-frog alkaloids 233A, 235U, and 251AA and their inhibitory effects on neuronal nicotinic acetylcholine receptors.
We previously reported that the synthetic quinolizidine 1-epi-207I is a relatively selective blocker of alpha7 nicotinic acetylcholine receptors. We now synthesized the analogous poison frog alkaloids 233A, 235U, and 251AA, and investigated the biological activities at two major types of neuronal nicotinic receptors. Electrophysiological study showed that the alkaloid 233A blocked alpha7 and alpha4beta2 currents with similar potencies. Alkaloids 235U and 251AA also showed similar potencies for blockade of alpha7 and alpha4beta2 currents. Thus, based on these studies, it would appear that C4 substituents greater in length than the allyl of 1-epi-207I reduce alpha7-potency without affecting alpha4beta2-potency.
Toyooka
Naoki
N
Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan. toyooka@pha.u-toyama.ac.jp
Kobayashi
Soushi
S
Zhou
Dejun
D
Tsuneki
Hiroshi
H
Wada
Tsutomu
T
Sakai
Hideki
H
Nemoto
Hideo
H
Sasaoka
Toshiyasu
T
Garraffo
H Martin
HM
Spande
Thomas F
TF
Daly
John W
JW
D000470:Alkaloids / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D001001:Anura; D002849:Chromatography, Gas; D009474:Neurons / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D014982:Xenopus laevis