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
Related Articles
- EP ID EP123597
- DOI -
- Views 96
- Downloads 0
Effects of GABAB receptor agonists on cocaine hyperlocomotor and sensitizing effects in rats.
The present study was designed to find out whether pharmacological activation of GABA(B) receptors played a role in cocaine sensitization. To this end, male Wistar rats were injected with baclofen or 3-aminopropyl(methyl...
Protective effect of α-lipoic acid on oxidized low density lipoprotein-induced human umbilical vein endothelial cell injury.
The present study investigated the effect and possible mechanisms of α-lipoic acid (LA) in preventing endothelial cell injury induced by oxidized low-density lipoprotein (oxLDL). A model of human umbilical vein endotheli...
Plasma concentrations of adhesion molecules and chemokines in patients with essential hypertension.
Arterial hypertension vascular injury results in serious complications, such as left-ventricular hypertrophy and myocardial failure, ischemic heart disease and cerebral stroke. Currently, it is well known that inflammato...
Anthracycline-induced cardiotoxicity: Overview of studies examining the roles of oxidative stress and free cellular iron.
The risk of cardiotoxicity is the most serious drawback to the clinical usefulness of anthracycline antineoplastic antibiotics, which include doxorubicin (adriamycin), daunorubicin or epirubicin. Nevertheless, these comp...
Dose-response relationship analysis of pregabalin doses and their antinociceptive effects in hot-plate test in mice.
The aim of this study was to determine the analgesic effects of pregabalin (a third-generation antiepileptic drug) using the acute thermal pain model (hot-plate test) in mice. Linear regression analysis was used to evalu...