In vitro and in vivo binding of (E)- and (Z)-N-(iodoallyl)spiperone to dopamine D2 and serotonin 5-HT2 neuroreceptors

John R. Lever, Ursula A. Scheffel, Marigo Stathis, John L. Musachio, Henry N. Wagner

Research output: Contribution to journalArticlepeer-review

Abstract

Apparent affinities (Ki) of (E)- and (Z)-N-(iodoallyl)spiperone ((E)- and (Z)-NIASP) for dopamine D2 and serotonin 5-HT2 receptors were determined in competition binding assays. (Z)-NIASP (Ki 0.35 nM, D2; Ki 1.75 nM, 5-HT2) proved slightly more potent and selective for D2 sites in vitro than (E)-NIASP (Ki 0.72 nM, D2; Ki 1.14 nM, 5-HT2). In vivo, radioiodinated (E)- and (Z)-[125I]-NIASP showed regional distributions in mouse brain which are consonant with prolonged binding to dopamine D2 receptors accompanied by a minor serotonergic component of shorter duration. Stereoselective, dose-dependent blockade of (E)-[125I]-NIASP uptake was found for drugs binding to dopamine D2 sites, while drugs selective for serotonin 5-HT2, α1- adrenergic and dopamine D1 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)-[125I]-NIASP gave a striatal to cerebellar tissue radioactivity concentration of 16.9 to 1 at 6 hr postinjection. Thus, (E)-[125I]-NIASP binds with high selectivity and specificity to dopamine D2 sites in vivo.

Original languageEnglish (US)
Pages (from-to)1967-1976
Number of pages10
JournalLife Sciences
Volume46
Issue number26
DOIs
StatePublished - 1990

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Fingerprint Dive into the research topics of 'In vitro and in vivo binding of (E)- and (Z)-N-(iodoallyl)spiperone to dopamine D<sub>2</sub> and serotonin 5-HT<sub>2</sub> neuroreceptors'. Together they form a unique fingerprint.

Cite this