A new series of azabicyclic benzimidazole-4-carboxamides 2-21 and -carboxylates 22-30 were synthesized and evaluated for binding affinity at serotoninergic 5-HT(3) and 5-HT(4) receptors in the CNS. Most of the synthesized compounds exhibited high or very high affinity for the 5-HT(3) binding site and low to no significant affinity for the 5-HT(4) receptor. SAR observations indicated that a halogen atom at the 6-position and a nitro group at the 7-position of the benzimidazole ring is the best substitution pattern for 5-HT(3) affinity and 5-HT(3)/5-HT(4) selectivity, as well as no substitution in this ring. (S)-(-)-N-(Quinuclidin-3-yl)benzimidazole-4-carboxamides 2, 8, and 14 bound at central 5-HT(3) sites with high affinity (K(i) = 2.6, 0. 13, and 1.7 nM, respectively) and excellent selectivity over serotonin 5-HT(4) and 5-HT(1A) receptors (K(i) > 1000-10000 nM). Furthermore, these new 5-HT(3) receptor ligands were pharmacologically characterized as potent and selective 5-HT(3) antagonists in the isolated guinea pig ileum (pA(2) = 9.6, 9.9, and 9.1, respectively).