title: Synthesis and characterization of iodobenzamide analogues: potential D-2 dopamine receptor imaging agents.
abstract: (S)-N-[(1-Ethyl-2-pyrrolidinyl)methyl]-2-hydroxy-3-iodo-6- methoxybenzamide ([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 Kd 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 greater than IBF (21) greater than IBZM greater than (+)-butaclamol greater than (+/-)-ADTN,6,7 greater than ketanserin greater than SCH-23390 much greater than 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.
authors: Department of Radiology, University of Pennsylvania, Philadelphia 19104.
authors: R A
authors: RA
authors: Murphy
authors: H F
authors: HF
authors: Kung
authors: M P
authors: MP
authors: Kung
authors: J
authors: J
authors: Billings
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000138:chemical synthesis / Q000378:metabolism*; D001667:Binding, Competitive; D055598:Chemical Phenomena; D002621:Chemistry; D003342:Corpus Striatum / Q000378:metabolism; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D008297:Male; D015394:Molecular Structure; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D014018:Tissue Distribution
chemical_list: D001572:Benzofurans; D007457:Iodine Radioisotopes; D011759:Pyrrolidines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; C062439:5-iodo-N-((1-ethyl-2-pyrrolidinyl)methyl)-2,3-dihydrobenzofurancarboxamide