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 04:00:00 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), Journal Name: Life Sciences; (USA) Vol. 46:26; ISSN 0024-3205; ISSN LIFSA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
DAYS LIVING RADIOISOTOPES
DOPAMINE
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IN VITRO
IN VIVO
INDOLES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MEMBRANE PROTEINS
MICE
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
PROTEINS
PYRROLES
RADIOASSAY
RADIOISOTOPES
RADIOPROTECTIVE SUBSTANCES
REACTION KINETICS
RECEPTORS
RODENTS
SEROTONIN
SPIPERONE
SYMPATHOMIMETICS
TRACER TECHNIQUES
TRYPTAMINES
VERTEBRATES