Comparison of Typical and Atypical Benzodiazepines on the Central and Peripheral Benzodiazepine Receptors

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The affinities of typical and atypical benzodiazepines (BZs) for ³H-flunitrazepam (FLU) and ³H-Ro 5-4864, “peripheral” BZ, binding sites in the central nervous system (CNS) were compared. Each dissociation constant (K_d) value of the ³H-FLU binding sites in the cerebellum, cortex, hippocampus and spinal cord showed the similar results, although the binding maximum (B_max) for the cortex and cerebellum yielded the largest value and the smallest B_max appeared in the spinal cord. In contrast, B_max for ³H-Ro 5-4864 binding sites were about three-fold higher in the spinal cord than in the cerebellum. Among the drugs tested, brotizolam demonstrated the highest affinity for ³H-FLU binding sites in the four regions. Typical and atypical BZs did not normally show different affinities for the two BZ receptor subtypes, except for CL 218, 872 and Ro 5-4864. A series of compounds including Ro 5-4864, PK 11195, diazepam and brotizolam had high affinity for the ³H-Bo 5-4864 binding sites in the cerebellum and spinal cord. Other BZs did not show affinity for “peripheral” BZ binding sites in the CNS. In conclusion, brotizolam (or atypical BZ) had the binding affinity to both “central” and “peripheral” BZ receptors, like diazepam (a typical BZ).