In vitro and in vivo binding of (E)- and (Z)-N-(iodoallyl)spiperone to dopamine D sub 2 and serotonin 5-HT sub 2 neuroreceptors

Journal Article · Mon Jan 01 00:00:00 EST 1990 · Life Sciences; (USA)

DOI:https://doi.org/10.1016/0024-3205(90)90513-Q· OSTI ID:6650452

Lever, J R; Scheffel, U A; Stathis, M; Musachio, J L; Wagner, Jr, H N ^[1]

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1. Johns Hopkins Univ., Baltimore, MD (USA)

Apparent affinities (K{sub i}) of (E)- and (Z)-N-(iodoallyl)spiperone ((E)- and (Z)- NIASP) for dopamine D{sub 2} and serotonin 5-HT{sub 2} receptors were determined in competition binding assays. (Z)-NIASP (K{sub i} 0.35 nM, D{sub 2}; K{sub i} 1.75 nM, 5-HT{sub 2}) proved slightly more potent and selective for D{sub 2} sites in vitro than (E)-NIASP (K{sub i} 0.72 nM, D{sub 2}; K{sub i} 1.14 nM, 5-HT{sub 2}). In vivo, radioiodinated (E)- and (Z)-({sup 125}I)-NIASP showed regional distributions in mouse brain which are consonant with prolonged binding to dopamine D{sub 2} receptors accompanied by a minor serotonergic component of shorter duration. Stereoselective, dose-dependent blockade of (E)-({sup 125}I)-NIASP uptake was found for drugs binding to dopamine D{sub 2} sites, while drugs selective for serotonin 5-HT{sub 2}, {alpha}{sub 1}-adrenergic and dopamine D{sub 1} receptors did not inhibit radioligand binding 2 hr postinjection. Specific binding in striatal tissue was essentially irreversible over the time course of the study, and (E)-({sup 125}I)-NIASP gave a striatal to cerebellar tissue radioactivity concentration of 16.9 to 1 at 6 hr postinjection. Thus, (E)-({sup 125}I)-NIASP binds with high selectivity and specificity to dopamine D{sub 2} sites in vivo.

• OSTI ID: 6650452
• Journal Information: Life Sciences; (USA), Vol. 46:26; ISSN 0024-3205
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
DOPAMINE
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SEROTONIN
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BIOCHEMICAL REACTION KINETICS
BRAIN
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IN VITRO
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RADIOASSAY
TRACER TECHNIQUES
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BETA DECAY RADIOISOTOPES
BODY
CARDIOTONICS
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CENTRAL NERVOUS SYSTEM
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DRUGS
ELECTRON CAPTURE RADIOISOTOPES
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INDOLES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
PROTEINS
PYRROLES
RADIOISOTOPES
RADIOPROTECTIVE SUBSTANCES
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550201* - Biochemistry- Tracer Techniques