Effect of BD 1047, a sigma(1) receptor antagonist, in the animal models predictive of antipsychotic activity.

Apply

Effect of BD 1047, a sigma(1) receptor antagonist, in the animal models predictive of antipsychotic activity.

Journal Title: Pharmacological Reports - Year 2006, Vol 58, Issue 5

Abstract

The sigma receptors were first classified as a subtype of opioid receptors but later they were found to be a distinct pharmacological entity. Many preclinical and clinical data have indicated that sigma receptor ligands have to be involved in neuropsychiatric disorders, including schizophrenia. Numerous data have suggested that potential antipsychotic activity of sigma ligands results from their "antagonistic" activity. However, the subcellular mechanisms by which sigma ligands exert their effects have not been elucidated in detail, therefore, the terms "agonist" or "antagonist" and their functional implications are not entirely unequivocal. The aim of the present study was to findout if BD 1047, described recently as a selective functional antagonist of sigma receptors, shows antipsychotic activity in animal models predictive of efficacy in schizophrenia. In contrast to rimcazole and panamesine, two selective sigma ligands whose antipsychotic activity was confirmed clinically, BD 1047 did not decrease amphetamine-induced hyperactivity in mice in a statistically significant manner. Likewise, it did not modify the hyperactivity induced by NMDA receptor antagonists, phencyclidine, memantine or dizocilpine. On the other hand, BD 1047 attenuated apomorphine-induced climbing in mice and phencyclidine-induced head twitches in rats, like rimcazole and panamesine did. Summing up, BD 1047 shows a moderate activity in models used in this study suggesting that its usefulness as an antipsychtic drug is doubtful. However, more detailed studies are required for definitive confirmation of this conclusion.

Authors and Affiliations

Grażyna Skuza, Zofia Rogóż

Keywords

Impact of early-life stress on the medial prefrontal cortex functions - a search for the pathomechanisms of anxiety and mood disorders.

Although anxiety and mood disorders (MDs) are the most common mental diseases, the etiologies and mechanisms of these psychopathologies are still a matter of debate. The medial prefrontal cortex (mPFC) is a brain structu...

Can the antiplatelet effects of cangrelor be reliably studied in mice under in vivo and in vitro conditions using flow cytometry?

The effects of blood platelet inhibitors are often not quite equivalent under in vivo and in vitro conditions. Amongst various models of human pathology using laboratory animals, mice offer several benefits that make the...

EP ID EP123597
DOI -
Views 78
Downloads 0