Benzodiazepines (BZs) 2 are used clinically as muscle relaxants, anticonvulsants, anxiolytics, and sedativehypnotics. These effects are mediated primarily via the central BZ receptors (CBRs) located in the central nervous system (CNS; Braestrup and Squires, 1977; Möhler and Okada, 1977; Tallman et al., 1980). CBRs are part of a macromolecular complex that also contains a-aminobutyric acid (GABA) receptor site and a chloride ion channel (DeLorey and Olsen, 1992). This complex has been purified, its cDNA has been cloned, and its functional receptors have been expressed in Xenopus oocytes (Schofield et al., 1987). The GABA/BZ receptor complex is a hetero-oligomer composed of five subunits:-,-,-,-, and-polypeptides. BZs bind to the-subunit and facilitate the inhibitory effect obtained by GABA (DeLorey and Olsen, 1992).

BZs also bind to other receptors, located mainly in peripheral tissues and glial cells in the brain (Fig. 1), called peripheral BZ receptors (PBRs; Verma and Snyder, 1989; Gavish et al., 1992). In rats, PBRs differ from CBRs in their drug specificity: for example, the BZ clonazepam binds to CBRs with high affinity, whereas the BZ Ro 5-4864 (4-chlorodiazepam) as well as the non-BZ ligand PK 11195 (an isoquinoline carboxamide derivative) bind to CBRs with negligible affinity. The reverse is true with regard to PBRs (Benavides et al., 1983a, b). Imidazopyridines such as alpidem bind with high affinity to both CBRs and PBRs (Langer and Arbilla, 1988). FGIN-1 (2-aryl-3-indoleacetamide) binds with high affinity to PBRs but not to CBRs (Romeo et al., 1992). The focus of the current review is the PBR. The binding of PK 11195 and Ro 5-4864 has been studied in various species (Anholt et al., 1985b; Basile et al., 1986; Cymerman et al., 1986; Awad and Gavish, 1987, 1991; Parola et al., 1991). The binding of Ro 5-4864 has been found to differ among species (Awad and Gavish, 1987; Table 1). The order of potency of Ro 5-4864 in