The effects of PK 11195, a ligand for benzodiazepine binding sites, in animal tests of anxiety and stress.

PK 11195 (1-(2-chlorophenyl)-N-methyl-(1-methylpropyl)-3-isoquinolinecarboxami de, a potent ligand for peripheral benzodiazepine binding sites, was unable to reverse the anxiogenic effects of Ro 5-4864 (chlorodiazepam) in the social interaction test or in the punished drinking test. However, at 90 mg/kg PK 11195 also reduced social interaction, indicating an anxiogenic effect. Both PK 11195 (30-120 mg/kg) and Ro 5-4864 (20-60 mg/kg) significantly increased the plasma corticosterone concentrations of rats left in their home cages after injection, and in those placed in novel apparatus. Because both drugs had effects in the same direction and because the doses were far higher than those needed to saturate the peripheral receptor, it is unlikely that these behavioural actions are mediated by peripheral benzodiazepine binding sites. It is suggested that the effect of PK 11195 could even be mediated by the classical CNS benzodiazepine binding sites.