Characterization and distribution of (125I)epidepride binding to dopamine D2 receptors in basal ganglia and cortex of human brain

Journal Article · Sat Jun 01 00:00:00 EDT 1991 · Journal of Pharmacology and Experimental Therapeutics; (United States)

OSTI ID:5595694

Joyce, J N; Janowsky, A; Neve, K A ^[1]

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1. Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia (USA)

The distribution and pharmacology of the binding of {sup 125}I-epidepride, a substituted benzamide with high affinity and selectivity for dopamine (DA) D2 receptors in rat brain is described in human brain. Saturation analysis of the binding of {sup 125}I-epidepride to membranes derived from striatum and regions of cortex demonstrated similar Kd values (34 and 28-33 pM, respectively) but differing maximum density of binding site values (152 and 3-8 fmol/mg of protein, respectively). The pharmacological profile of binding in cortex was also similar to striatum (epidepride greater than spiperone greater than butaclamol = flupenthixol greater than clozapine) except that an additional low-affinity site, blocked by the alpha-2 adrenergic antagonist idazoxan, was present in cortex. Quantification by autoradiography also demonstrated the greatest binding in the basal ganglia, with the striatum exhibiting greater binding than the pallidal complex or midbrain regions. For the pallidum, binding in the external segment was higher than the internal segment. Within the midbrain the binding of {sup 125}I-epidepride correlated well with the known distribution of DA-containing cell bodies, with the substantia nigra (pars compacta and pars lateralis) and ventral tegmental area (A10) higher than area A8 and central gray. Binding in frontal and parietal cortex was highest in the internal layers (layers V and VI). Temporal cortex showed a 2-fold higher density of binding than other cortical regions and a trilaminar pattern; binding was greater in the external (layers I and II) and internal layers than in the middle layers (III and IV). This pattern changed in the parahippocampal complex. Within the lateral occipitotemporal cortex, binding was densest in layers I to III and very low in layers IV to VI, but binding was almost nonexistent in the adjacent entorhinal cortex.

• OSTI ID: 5595694
• Journal Information: Journal of Pharmacology and Experimental Therapeutics; (United States), Vol. 257:3; ISSN 0022-3565
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
AMIDES
BIOCHEMICAL REACTION KINETICS
DOPAMINE
RECEPTORS
AUTORADIOGRAPHY
CEREBRAL CORTEX
HIPPOCAMPUS
IN VITRO
IODINE 125
MAN
NERVE CELLS
PHARMACOLOGY
PYRROLIDINES
RADIOASSAY
TISSUE DISTRIBUTION
TRACER TECHNIQUES
AMINES
ANIMAL CELLS
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZOLES
BETA DECAY RADIOISOTOPES
BODY
BRAIN
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
CEREBRUM
DAYS LIVING RADIOISOTOPES
DISTRIBUTION
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
PRIMATES
PROTEINS
PYRROLES
RADIOISOTOPES
REACTION KINETICS
SOMATIC CELLS
SYMPATHOMIMETICS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques