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

Psychopharmacology (Berl). 1990;102(1):17-20. doi: 10.1007/BF02245738.


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.

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Behavior, Animal / drug effects*
  • Body Temperature / drug effects
  • Brain Chemistry / drug effects
  • Male
  • Mice
  • Phosphodiesterase Inhibitors / metabolism
  • Phosphodiesterase Inhibitors / pharmacology*
  • Pyrrolidinones / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Reserpine / antagonists & inhibitors
  • Rolipram


  • Antidepressive Agents
  • Phosphodiesterase Inhibitors
  • Pyrrolidinones
  • Reserpine
  • Rolipram