Abstract

The pharmacological profile and regional distribution of sigma receptors in human autopsy brains were determined using [3H]-haloperidol as the ligand, in the presence of 50 nM spiperone to block binding to D2 dopamine sites. Specific binding in the cerebellum was to a single and saturable class of receptors with Kd = 0.95 +/- 0.12 nM and maximum binding = 358 +/- 13 fmol/mg of protein. Inhibition studies of the nondopamine [3H]haloperidol binding site in human cerebellar membranes revealed stereospecific binding and a pharmacological profile similar to that of specific sigma binding sites characterized in rodent brains using [3H]haloperidol, N-[3H]allylnormetazocine and di-o-[3H]-tolylguanidine as radioligands. The densities of sigma sites in the brain were highest in the cerebellum, nucleus accumbens and cerebral cortex. A post-mortem simulation study was performed with guinea pig brains due to the concern that sigma receptors might deteriorate in the human brain before assay. The results showed that this site was remarkably stable and insensitive to long periods of cooling or freezing.