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Abstract

Characterization and distribution of [125I]epidepride binding to dopamine D2 receptors in basal ganglia and cortex of human brain.

J N Joyce, A Janowsky and K A Neve
Journal of Pharmacology and Experimental Therapeutics June 1991, 257 (3) 1253-1263;
J N Joyce
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A Janowsky
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K A Neve
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Abstract

The distribution and pharmacology of the binding of [125I]epidepride, a substituted benzamide with high affinity and selectivity for dopamine (DA) D2 receptors in rat brain (Neve et al., J. Pharmacol. Exp. Ther. 252: 1108-1116, 1990), is described in human brain. Saturation analysis of the binding of [125I]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 [125I]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. Within the hippocampal complex, binding was evident in the subiculum, CA3 and dentate gyrus and almost nonexistent in the presubiculum or other fields of the hippocampus. This pattern of binding in the parahippocampal gyrus is unique to human brain and represents sites of action for DA in limbic cortex.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 257, Issue 3
1 Jun 1991
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Abstract

Characterization and distribution of [125I]epidepride binding to dopamine D2 receptors in basal ganglia and cortex of human brain.

J N Joyce, A Janowsky and K A Neve
Journal of Pharmacology and Experimental Therapeutics June 1, 1991, 257 (3) 1253-1263;

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Abstract

Characterization and distribution of [125I]epidepride binding to dopamine D2 receptors in basal ganglia and cortex of human brain.

J N Joyce, A Janowsky and K A Neve
Journal of Pharmacology and Experimental Therapeutics June 1, 1991, 257 (3) 1253-1263;
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