Sigma binding states in the brain; An emerging concept for multiple sites and their relevance for psychiatric disorders

Yossef Itzhak, Ira Stein

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

An increasing amount of evidence suggests the existence of specific binding sites for psychotomimetic drugs from the opiate-benzomorphan and arylcyclohexylamine series. The sigma binding sites have preferential affinity for the dextrorotatory isomers of certain opiate benzomorphans, such as (+)SKF 10047, (+)Cyclazocine and (+)pentazocine and also for some neuroleptics (e.g., haloperidol). The PCP receptor has preferential affinity for phencyclidine (PCP) analogs and other non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists. The physiological significance of the PCP receptor is associated with the blockade of the NMDA type of the glutamate receptor, implying a neuroprotective role of the PCP receptor. However, the significance of the sigma binding sites is less conspicuous. It is not only that drugs from distinct pharmacological classes display a certain degree of affinity for the "sigma/haloperidol" binding sites, but also that drugs which do not induce or block psychotomimetic activity, i.e., (+)3-(3-hydroxyphenyl)-N-(1-propyl) piperidine [(+)3-PPP] and 1,3-di-o-tolyl-guanidine (DTG), display relatively high affinity for the sigma binding sites. The diversity of the compounds which are proposed to interact with the sigma receptors and the variety of the responses elicited by these drugs suggest the existence of sigma receptor subtypes. The finding that the type of monoamine oxidase (MAO) inhibitors, which are used in treatment of affective disorders, display high affinity for the sigma binding sites suggests their involvement in affective or schizoaffective disorders. Revealing the existence of sigma receptor subtypes may help to elucidate their association with various psychiatric disorders.

Original languageEnglish
Pages (from-to)1073-1081
Number of pages9
JournalLife Sciences
Volume47
Issue number13
DOIs
StatePublished - Jan 1 1990

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Psychiatry
Brain
Phencyclidine Receptors
Binding Sites
sigma Receptors
Opiate Alkaloids
Benzomorphans
Haloperidol
N-Methyl-D-Aspartate Receptors
Mood Disorders
Pharmaceutical Preparations
Cyclazocine
Pentazocine
Phencyclidine
Monoamine Oxidase Inhibitors
Guanidine
Glutamate Receptors
N-Methylaspartate
Isomers
Psychotic Disorders

ASJC Scopus subject areas

  • Pharmacology

Cite this

Sigma binding states in the brain; An emerging concept for multiple sites and their relevance for psychiatric disorders. / Itzhak, Yossef; Stein, Ira.

In: Life Sciences, Vol. 47, No. 13, 01.01.1990, p. 1073-1081.

Research output: Contribution to journalArticle

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