Cerebral metabolic effects of sigma ligands in the rat.

The 2-deoxy-D-[1-14C]glucose method was used to study the effects of sigma-type drugs, BMY 14802, (+)-pentazocine and BW 234U (rimcazole), on cerebral metabolism in 44 male Fischer 344 rats. Drug effects were observed in epithalamic, methathalamic, hypothalamic and mesencephalic regions, as well as in cranial nerve nuclei, the cerebellum, and the medulla oblongata. BMY 14802 and (+)-pentazocine increased local cerebral glucose utilization (LCGU) in areas that generally did not overlap; BW 234U administered 30 min before the radiotracer decreased LCGU. Most of the areas that showed changes in LCGU are known to contain sigma receptor sites. Differences in pharmacological properties, including effects on neuronal electrical excitability, may have resulted in the different distributions and effects of the drugs on LCGU. The present findings did not discriminate the compounds as agonists or antagonists for sigma receptor sites. However, the 2-deoxy-D-[1-14C]glucose method appeared useful in delineating the distribution of CNS responses to sigma drugs in the rat.