High affinity dopamine D2 receptor radioligands. 1. Regional rat brain distribution of iodinated benzamides

Journal Article · Thu Aug 01 04:00:00 EDT 1991 · Journal of Nuclear Medicine; (United States)

OSTI ID:5189617

Kessler, R M; Ansari, M S; de Paulis, T; Schmidt, D E; Clanton, J A; Smith, H E; Manning, R G; Gillespie, D; Ebert, M H ^[1]

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1. Vanderbilt University School of Medicine, Nashville, TN (USA)

Five 125I-labeled substituted benzamides, which are close structural analogues of (S)-sulpiride, eticlopride, and isoremoxipride, were evaluated for their selective in vivo uptake into dopamine D2 receptor rich tissue of the rat brain. Iodopride (KD 0.88 nM), an iodine substituted benzamide structurally related to sulpiride, displayed a maximal striatum: cerebellar uptake ratio of 7.6. Demonstration of saturation of the receptor with (125I)iodopride in striatum required uptake in frontal cortex to be used, rather than cerebellar uptake, to define nonspecific binding. Two other ligands structurally related to eticlopride, iclopride (KD 0.23 nM) and itopride (KD 0.16 nM), displayed maximal striatal: cerebellar uptake ratios of 9.8 and 3.3, respectively. The most potent ligands, epidepride (KD 0.057 nM) and ioxipride (KD 0.070 nM) showed striatal:cerebellar uptake ratios of 234 and 65, respectively. The observed uptake ratios correlated poorly with the affinity constants for the dopamine D2 receptor alone, but were highly correlated (r = 0.92) with the product of the receptor dissociation constant (KD) and the apparent lipophilicity (kw), as determined by reverse-phase HPLC at pH 7.5. Total striatal uptake also appeared dependent on lipophilicity, with maximal uptake occurring for ligands having log kw 2.4-2.8.

• OSTI ID: 5189617
• Journal Information: Journal of Nuclear Medicine; (United States), Journal Name: Journal of Nuclear Medicine; (United States) Vol. 32:8; ISSN 0161-5505; ISSN JNMEA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BODY
BRAIN
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
CHROMATOGRAPHY
COMPUTERIZED TOMOGRAPHY
DAYS LIVING RADIOISOTOPES
DIAGNOSTIC TECHNIQUES
DISTRIBUTION
DOPAMINE
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
EMISSION COMPUTED TOMOGRAPHY
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE 125
IODINE ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
LIGANDS
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
PROTEINS
RADIOISOTOPES
RADIOPHARMACEUTICALS
RATS
RECEPTORS
RODENTS
SEPARATION PROCESSES
SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY
SYMPATHOMIMETICS
TISSUE DISTRIBUTION
TOMOGRAPHY
VERTEBRATES