Sigma binding states in the brain; An emerging concept for multiple sites and their relevance for psychiatric disorders
Life Sciences 1990 DOI: 10.1016/0024-3205(90)90165-n (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Citations | 99 |
| Key findings | The authors argue that sigma binding sites show high affinity for dextrorotatory opiate benzomorphans and haloperidol, while the PCP receptor binds phencyclidine analogs and non-competitive NMDA antagonists and may be neuroprotective. They propose that the diversity of compounds interacting with sigma sites, including non-psychotomimetic drugs such as (+)3-PPP and DTG, suggests the existence of sigma receptor subtypes, and that high-affinity binding by type A monoamine oxidase inhibitors points to involvement in affective or schizoaffective disorders. |
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 A 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.