In this study, the effects of different peripheral benzodiazapine receptor
ligands:
PK 11195 [1-(2-chloro-phenyl)-N-methyl-N-(1-methylpropyl)-1-
isoquinoline carboxamide],
Ro5-4864 [7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one] and the newly described
SSR 180575 (7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridozine[4,5-b]
indole-1-
acetamide) were analysed on the progression and severity of
rheumatoid arthritis in vivo in the Mrl/lpr mice model, following chronic treatment (at 3 mg/kg, i.p. for 30 days). We found that peripheral
benzodiazepine receptor ligands have significant beneficial therapeutic action on the development of spontaneous
rheumatoid arthritis-like signs. Concomitantly, we mapped immunoreactive peripheral
benzodiazepine receptor in inflamed tissues, and we observed that in addition to the infiltrated leukocytes, peripheral
benzodiazepine receptor was expressed in synovial membranes, at the cartilage pannus junction and in chondrocytes. Interestingly, we observed that peripheral
benzodiazepine receptor expression in chondrocytes was reduced when Mrl/lpr mice developed the pathology and restored upon peripheral
benzodiazepine receptor ligand treatment. Altogether, our data provide further evidence of a role played by peripheral
benzodiazepine receptor in the regulation of
inflammation processes and support new therapeutic applications for specific potent peripheral
benzodiazepine receptor ligands.