(+)‐[3H]MK‐801 Binding Sites in Postmortem Human Brain

: The pharmacological specificity and the regional distribution of the N‐methyl‐D‐aspartate receptor‐associated 5‐methyl‐10,11‐dihydro‐5H‐dibenzo[a,d]cyclohepten‐5, 10‐imine maleate (MK‐801) binding sites in human postmortem brain tissue were determined by binding studies using (+)‐[3H]MK‐801. Scatchard analysis revealed a high‐affinity (KD= 0.9 ± 0.2 nM, Bmax= 499 ± 33 fmol/mg of protein) and a low‐affinity (KD= 3.6 ± 0.9 nM, Bmax= 194 ± 44 fmol/ mg of protein) binding site. The high‐affinity site showed a different regional distribution of receptor density (cortex > hippocampus > striatum) compared to the low‐affinity binding site (cerebellum > brainstem). The rank order pharmacological specificity and stereoselectivity of the high‐(cortex) and low‐(cerebellar) affinity binding sites were identical. However, all compounds tested showed greater potency at the high‐affinity site in cortex. The results indicate that (+)[3H]MK‐801 binding in human postmortem brain tissue shows pharmacological and regional specificity.