High affinity dopamine D2 receptor radioligands. 2. ( sup 125 I)epidepride, a potent and specific radioligand for the characterization of striatal and extrastriatal dopamine D2 receptors
- Vanderbilt Univ., Nashville, TN (United States)
- Yale Univ., New Haven, CT (United States)
Epidepride, (S)-N-((1-ethyl-2-pyrrolidinyl)methyl)-5-iodo-2,3-dimethoxybenzamide, the iodine analogue of isoremoxipride (FLB 457), was found to be a very potent dopamine D2 receptor antagonist. Optimal in vitro binding required incubation at 25C for 4 h at pH 7.4 in a buffer containing 120 mM NaCl, 5 mM KCl, 2 mM CaCl{sub 2} and 1 nM MgCl{sub 2}. Scatchard analysis of in vitro binding to striatal, medical frontal cortical, hippocampal and cerebellar membranes revealed a K{sub D} of 24 pM in all regions, with Bmax's of 36.7, 1.04, 0.85, and 0.37 pmol/g tissue, respectively. The Hill coefficients ranged from 0.91-1.00 in all four regions. The IC{sub 50}'s for inhibition of ({sup 125}I)epidepride binding to striatal, medial frontal cortical, and hippocampal membranes for SCH 23390, SKF 83566, serotonin, ketanserin, mianserin, naloxone, QNB, prasozin, clonidine, alprenolol, and norepinephrine ranged from 1 {mu}M to >10 {mu}M. Partial displacement of ({sup 125}I)epidepride by nanomolar concentrations of clonidine was noted in the frontal cortex and hippocampus, but not in the striatum. Scatchard analysis of epidepride binding to {alpha}{sub 2} noradrenergic receptors in the frontal cortex and hippocampus revealed an apparent K{sub D} of 9 nM. At an epidepride concentration equal to the K{sub D} for the D2 receptor, i.e., 25 pM, no striatal {alpha}{sub 2} binding was seen and only 7% of the specific epidepride binding in the cortex or hippocampus was due to binding at the {alpha}{sub 2} site. Correlation of inhibition of ({sup 3}H)spiperone and ({sup 125}I)epidepride binding to striatal membranes by a variety of D2 ligands revealed a correlation coefficient of 0.99, indicating that epidepride labels a D2 site.
- OSTI ID:
- 5699089
- Journal Information:
- Life Sciences; (United States), Vol. 49:8; ISSN 0024-3205
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
DOPAMINE
RECEPTORS
CHEMICAL COMPOSITION
BIOCHEMICAL REACTION KINETICS
BRAIN
CELL MEMBRANES
IODINE 125
LIGANDS
TRACER TECHNIQUES
AMINES
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BODY
CARDIOTONICS
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MEMBRANE PROTEINS
MEMBRANES
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
PROTEINS
RADIOISOTOPES
REACTION KINETICS
SYMPATHOMIMETICS
550201* - Biochemistry- Tracer Techniques