Binding of umespirone to the σ receptor: Evidence for multiple affinity states

Yossef Itzhak, M. Ruhland, H. Krähling

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Umespirone (3,7-diazabicyclo[3.3.1]nonane-2,4,6,8-tetraon; KC9172) has been recently described as a potential antipsychotic/anxiolytic. In the present study the interaction of umespirone and several other typical and atypical psychotropics with the o and phencyclidine (PCP) receptor subtypes, in rat brain membranes, was investigated. Umespirone, haloperidol, chlorpromazine and buspirone, but not clozapine and diazepam, compete for the binding of the σ-ligand, (+)[3H]-3-(3-hydroxy-phenyl)-N-1-(propyl) piperidine [(+)]3H-3-PPP]. The compounds do not compete for the binding of PCP-receptor ligands. Umespirone, buspirone and (+)-3-PPP, unlike haloperidol and chlorpromazine, inhibit (+)[3H]-3-PPP binding in a manner indicating the existence of high and low affinity states of the a receptor. 5′-Guanylylimidodiphosphate (Gpp(NH)p; 0.1mM) abolishes the high affinity binding component associated with the binding of umespirone, buspirone and (+)-3-PPP, but does not affect the affinities of haloperidol and chlorpromazine for the o receptor. These findings suggest that different coupling states of the o receptor may be associated with the binding of umespirone and buspirone compared to the binding of haloperidol and chlorpromazine.

Original languageEnglish
Pages (from-to)181-184
Number of pages4
JournalNeuropharmacology
Volume29
Issue number2
DOIs
StatePublished - Jan 1 1990
Externally publishedYes

Fingerprint

Buspirone
Phencyclidine Receptors
Haloperidol
Chlorpromazine
Guanylyl Imidodiphosphate
Ligands
Clozapine
Anti-Anxiety Agents
Diazepam
Antipsychotic Agents
umespirone
Membranes
preclamol
Brain

Keywords

  • 5′-guanylylimidodiphosphate
  • Antipsychotics
  • Anxiolytics
  • PCP receptor
  • Sigma receptor

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

Binding of umespirone to the σ receptor : Evidence for multiple affinity states. / Itzhak, Yossef; Ruhland, M.; Krähling, H.

In: Neuropharmacology, Vol. 29, No. 2, 01.01.1990, p. 181-184.

Research output: Contribution to journalArticle

Itzhak, Yossef ; Ruhland, M. ; Krähling, H. / Binding of umespirone to the σ receptor : Evidence for multiple affinity states. In: Neuropharmacology. 1990 ; Vol. 29, No. 2. pp. 181-184.
@article{5a1fac4d9ed7412b95b755423d5ec94a,
title = "Binding of umespirone to the σ receptor: Evidence for multiple affinity states",
abstract = "Umespirone (3,7-diazabicyclo[3.3.1]nonane-2,4,6,8-tetraon; KC9172) has been recently described as a potential antipsychotic/anxiolytic. In the present study the interaction of umespirone and several other typical and atypical psychotropics with the o and phencyclidine (PCP) receptor subtypes, in rat brain membranes, was investigated. Umespirone, haloperidol, chlorpromazine and buspirone, but not clozapine and diazepam, compete for the binding of the σ-ligand, (+)[3H]-3-(3-hydroxy-phenyl)-N-1-(propyl) piperidine [(+)]3H-3-PPP]. The compounds do not compete for the binding of PCP-receptor ligands. Umespirone, buspirone and (+)-3-PPP, unlike haloperidol and chlorpromazine, inhibit (+)[3H]-3-PPP binding in a manner indicating the existence of high and low affinity states of the a receptor. 5′-Guanylylimidodiphosphate (Gpp(NH)p; 0.1mM) abolishes the high affinity binding component associated with the binding of umespirone, buspirone and (+)-3-PPP, but does not affect the affinities of haloperidol and chlorpromazine for the o receptor. These findings suggest that different coupling states of the o receptor may be associated with the binding of umespirone and buspirone compared to the binding of haloperidol and chlorpromazine.",
keywords = "5′-guanylylimidodiphosphate, Antipsychotics, Anxiolytics, PCP receptor, Sigma receptor",
author = "Yossef Itzhak and M. Ruhland and H. Kr{\"a}hling",
year = "1990",
month = "1",
day = "1",
doi = "10.1016/0028-3908(90)90058-Y",
language = "English",
volume = "29",
pages = "181--184",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Elsevier Limited",
number = "2",

}

TY - JOUR

T1 - Binding of umespirone to the σ receptor

T2 - Evidence for multiple affinity states

AU - Itzhak, Yossef

AU - Ruhland, M.

AU - Krähling, H.

PY - 1990/1/1

Y1 - 1990/1/1

N2 - Umespirone (3,7-diazabicyclo[3.3.1]nonane-2,4,6,8-tetraon; KC9172) has been recently described as a potential antipsychotic/anxiolytic. In the present study the interaction of umespirone and several other typical and atypical psychotropics with the o and phencyclidine (PCP) receptor subtypes, in rat brain membranes, was investigated. Umespirone, haloperidol, chlorpromazine and buspirone, but not clozapine and diazepam, compete for the binding of the σ-ligand, (+)[3H]-3-(3-hydroxy-phenyl)-N-1-(propyl) piperidine [(+)]3H-3-PPP]. The compounds do not compete for the binding of PCP-receptor ligands. Umespirone, buspirone and (+)-3-PPP, unlike haloperidol and chlorpromazine, inhibit (+)[3H]-3-PPP binding in a manner indicating the existence of high and low affinity states of the a receptor. 5′-Guanylylimidodiphosphate (Gpp(NH)p; 0.1mM) abolishes the high affinity binding component associated with the binding of umespirone, buspirone and (+)-3-PPP, but does not affect the affinities of haloperidol and chlorpromazine for the o receptor. These findings suggest that different coupling states of the o receptor may be associated with the binding of umespirone and buspirone compared to the binding of haloperidol and chlorpromazine.

AB - Umespirone (3,7-diazabicyclo[3.3.1]nonane-2,4,6,8-tetraon; KC9172) has been recently described as a potential antipsychotic/anxiolytic. In the present study the interaction of umespirone and several other typical and atypical psychotropics with the o and phencyclidine (PCP) receptor subtypes, in rat brain membranes, was investigated. Umespirone, haloperidol, chlorpromazine and buspirone, but not clozapine and diazepam, compete for the binding of the σ-ligand, (+)[3H]-3-(3-hydroxy-phenyl)-N-1-(propyl) piperidine [(+)]3H-3-PPP]. The compounds do not compete for the binding of PCP-receptor ligands. Umespirone, buspirone and (+)-3-PPP, unlike haloperidol and chlorpromazine, inhibit (+)[3H]-3-PPP binding in a manner indicating the existence of high and low affinity states of the a receptor. 5′-Guanylylimidodiphosphate (Gpp(NH)p; 0.1mM) abolishes the high affinity binding component associated with the binding of umespirone, buspirone and (+)-3-PPP, but does not affect the affinities of haloperidol and chlorpromazine for the o receptor. These findings suggest that different coupling states of the o receptor may be associated with the binding of umespirone and buspirone compared to the binding of haloperidol and chlorpromazine.

KW - 5′-guanylylimidodiphosphate

KW - Antipsychotics

KW - Anxiolytics

KW - PCP receptor

KW - Sigma receptor

UR - http://www.scopus.com/inward/record.url?scp=0025177110&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025177110&partnerID=8YFLogxK

U2 - 10.1016/0028-3908(90)90058-Y

DO - 10.1016/0028-3908(90)90058-Y

M3 - Article

C2 - 1970425

AN - SCOPUS:0025177110

VL - 29

SP - 181

EP - 184

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

IS - 2

ER -