title: Neuroprotective and anti-amnesic potentials of sigma (sigma) receptor ligands.
abstract: 1. Although the physical nature of sigma (sigma) receptors have not yet been fully defined, several classes of selective ligands have been characterised, demonstrating a plethora of physiological actions. In the present review, the authors have set out to highlight two important aspects of the biological activities of sigma ligands, their neuroprotective and anti-amnesic effects. 2. The sigma ligands present a therapeutic potential as neuroprotective agents in brain ischemia. The neuroprotective activity of many non-selective sigma ligands is primarily a result of their affinity for the NMDA receptor complex. However, selective sigma ligands are also neuroprotective, possibly by inhibition of the ischemic-induced presynaptic release of excitotoxic amino acids. 3. The sigma 1 ligands prevent the experimental amnesia induced by muscarinic cholinergic antagonists at either the learning, consolidation or retention phase of the mnesic process. This effect involves a potentation of acetylcholine release induced by sigma 1 ligands selectively in the hippocampal formation and cortex. 4. The sigma 1 receptor ligands also attenuate the learning impairment induced by dizocilpine, a non-competitive antagonist of the NMDA receptor, and may relate to the potentiating effect of sigma 1 ligands on several NMDA receptor-mediated responses previously described in vitro and in vivo in the hippocampus. This effect is shared by NPY- and CGRP-related peptides and by neuroactive steroids, confirming the in vitro evidences of functional interactions between the sigma 1 receptors and these different systems. 5. Additional amnesia models also seem to be alleviated by sigma 1 ligands, such as phencyclidine-induced cognitive dysfunctions, and amnesia induced by the calcium channel blocker nimodipine, or by exposure to carbon monoxide. Furthermore, a preliminary study in an animal model of age-related memory deficits, the senescence-accelerated mouse, strengthened the therapeutic potentials of selective sigma 1 receptor ligands in aging-related pathologies.
authors.affiliation: INSERM U. 336, Développement, Plasticité et Vieillissement du Système Nerveux, ENSCM, Montpellier, France. maurice@cit.enscm.fr
authors.forename: T
authors.initials: T
authors.lastname: Maurice
authors.forename: B P
authors.initials: BP
authors.lastname: Lockhart
mesh_terms: D000647:Amnesia / Q000188:drug therapy*; D000818:Animals; D008024:Ligands; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017480:Receptors, sigma / Q000187:drug effects*
chemical_list: D008024:Ligands; D018696:Neuroprotective Agents; D017480:Receptors, sigma