The binding of arylguanidines at 5-HT3 serotonin receptors: a structure–affinity investigation

The 5-HT3 receptor binding affinities of nine pairs of aryl-substituted arylguanidines and arylbiguanides were examined and the results suggest the likelihood that both classes of agents utilize common receptor binding features. The effects of structural modification were also examined using CoMFA. 1-(3,4,5-Trichlorophenyl)guanidine (5-HT3Ki=0.7 nM) was identified as a very high-affinity arylguanidine. The structures of the high-affinity arylguanidines are inconsistent with current 5-HT3 pharmacophore models.