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 find out 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.