Dopamine D-2 receptor imaging radiopharmaceuticals: synthesis, radiolabeling and in vitro binding of (R)-(+)- and (S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide

In developing central nervous system (CNS) dopamine D-2 receptor imaging agents, enantiomers, R-(+) and S-(-) isomers, of 3-[125I]iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2- pyrrolidinyl)methyl]benzamide, [125I]IBZM, were synthesized, and their in vitro binding characteristics were evaluated in rat stri...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1988-05, Vol.31 (5), p.1039-1043
Main Authors: Kung, Hank F, Kasliwal, Ravindra, Pan, Sangren, Kung, Mei Ping, Mach, Robert H, Guo, Yu Zhi
Format: Article
Language:English
Subjects:
Animals
Benzamides - chemical synthesis
Benzamides - metabolism
Chemical Phenomena
Chemistry
Corpus Striatum - metabolism
Exact sciences and technology
Heterocyclic compounds
Heterocyclic compounds with only one n hetero atom and condensed derivatives
In Vitro Techniques
Iodine Radioisotopes
Male
Organic chemistry
Preparations and properties
Pyrrolidines - chemical synthesis
Pyrrolidines - metabolism
Rats
Rats, Inbred Strains
Receptors, Dopamine - metabolism
Receptors, Dopamine D2
Stereoisomerism
Structure-Activity Relationship
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Summary:In developing central nervous system (CNS) dopamine D-2 receptor imaging agents, enantiomers, R-(+) and S-(-) isomers, of 3-[125I]iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2- pyrrolidinyl)methyl]benzamide, [125I]IBZM, were synthesized, and their in vitro binding characteristics were evaluated in rat striatum tissue preparation. The (S)-(-)-[125I]IBZM showed high specific dopamine D-2 receptor binding (Kd = 0.43 nM, Bmax = 0.48 pmol/mg of protein). Competition data of various ligands for IBZM binding displayed the following rank order of potency: spiperone greater than (S)-(-)-IBZM greater than (+)-butaclamol much greater than (R)-(+)-IBZM greater than (S)-(-)-BZM greater than dopamine greater than ketanserin greater than SCH23390 much greater than propanolol. The results indicate that [125I]IBZM binds specifically to the dopamine D-2-receptor with stereospecificity. The [123I]IBZM is potentially useful as an imaging agent for the investigation of dopamine D-2 receptors in humans.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00400a027