Synthesis and characterization of iodobenzamide analogues: Potential D-2 dopamine receptor imaging agents

Article abstract of DOI:10.1021/jm00163a029

(S)-N-[(1-Ethyl-2-pyrrolidinyl)methyl]-2-hydroxy-3-iodo-6-methoxybenza mide ([¹²³I]IBZM) is a central nervous system (CNS) D-2 dopamine receptor imaging agent. In order to investigate the versatility of this parent structure in specific dopamine receptor localization and the potential for developing new dopamine receptor imaging agents, a series of new iodinated benzamides with fused ring systems, naphthalene (INAP) and benzofuran (IBF), was synthesized and radiolabeled, and the in vivo and in vitro biological properties were characterized. The best analogue of IBZM is IBF (21). The specific binding of [¹²⁵I]IBF (21) with rat striatal tissue preparation was found to be saturable and displayed a K(d) of 0.106 ± 0.015 nM. Competition data of various receptor ligands (for [¹²⁵I]IBF (21) binding show the following rank order of potency: spiperone > IBF (21) > IBZM > (+)-butaclamol > (±)-ADTN,6,7 > ketanserin > SCH-23390 >> propranolol. The in vivo biodistribution results confirm that [¹²⁵I]IBF (21) concentrated in the striatal area after iv injection into rats. The study demonstrates that [¹²³I]IBF (21) is a potential agent for imaging CNS D-2 dopamine receptors.