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.
Schmiechen
R
R
Research Laboratories of Schering AG, Department of Neuropsychopharmacology, Berlin.
Schneider
H H
HH
Wachtel
H
H
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D008297:Male; D051379:Mice; D010726:Phosphodiesterase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000037:antagonists & inhibitors; D020889:Rolipram
D000928:Antidepressive Agents; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D012110:Reserpine; D020889:Rolipram