Neosurugatoxin (NSTX) which contains two sugars (myoinositol and xylopyranose) and bromine in the chemical structure, has been shown previously to be a selective antagonist of nicotinic receptors in guinea pig ileum and in murine brain. To study the role of sugar moiety and bromine in the antinicotinic activity by NSTX, we have examined the action of NSTX (compound I) and the structurally related compounds (compound II, III and IV) on the nicotine-induced contraction of guinea pig isolated ileum and on specific [3H]nicotine binding in rat forebrain membranes. Among four compounds examined, compound I was the most potent in inhibiting the nicotine-induced contraction of guinea pig isolated ileum (pA2 = 9.1 +/- 0.1, pD2' = 8.0 +/- 0.1) and also in inhibiting specific [3H]nicotine binding in rat forebrain (IC50 = 83 +/- 9 9 nM). Compared to compound I, compound II and III which are devoid of one and two sugars, respectively, in the chemical structure of compound I were 2 or 3 times less potent in the antinicotinic activity in both tissues, and compound IV which lacks bromine in addition to two sugars was two orders of magnitude less potent. Thus, the present study demonstrates that bromine rather than sugar moiety in the chemical structure of compound I (NSTX) is an important determinate of its high affinity for nicotinic receptors.