Close correlation between behavioural response and binding in vivo for inhibitors of the rolipram-sensitive phosphodiesterase.

The antidepressant rolipram interacts in vitro with a binding site in brain tissue labeled by 3H-rolipram. A 3H-rolipram binding assay was employed in vivo to compare the affinity of rolipram-related compounds and reference phosphodiesterase (PDE) inhibitors with their potency in behavioural measures for potential antidepressant property. In two species, mice and rats, the potency of a number of compounds to antagonise reserpine-induced hypothermia (mice) and to induce head twitches (rats) was determined, as well as their potency to displace 3H-rolipram from forebrain binding sites in vivo. The treatment schedules for the two series of experiments were identical. Significant correlations between pharmacological effects and displacement of 3H-rolipram binding in vivo were observed in both species. Since the reference PDE inhibitors closely fit into the binding-pharmacological activity relationship, the PDE inhibitory properties of the substances involved are discussed.