Phosphodiesterase inhibitors--are they potential neuroleptic drugs?
It was suggested that phosphodiesterase (PDE) inhibitors may be potential neuroleptic drugs with a low risk of extrapyramidal symptoms. In the study presented, we compared the effects of the neuroleptics, haloperidol, and risperidone and the PDE10A inhibitor papaverine as well as the PDE4 inhibitor rolipram on retrieval of conditioned avoidance responding in the pole-jumping task and on locomotor activity. After acute administration, the substances used reduced locomotor activity dose-dependently. Both PDE inhibitors interfered with conditioned avoidance responding, suggesting neuroleptic-like effects. Risperidone showed a favourable profile of action. In all the doses tested, no signs of unspecific impairments in the performance of the instrumental task occurred. The profile of rolipram was similar. In the doses tested, only minor impairments in the performance of the instrumental task were found. Rolipram showed a similar effect to risperidone, suggesting therapeutic usefulness as an atypical neuroleptic. However, the use of this substance is limited by its emetic effects in therapeutically relevant doses.
Becker
Axel
A
Otto-von-Guericke University, Faculty of Medicine, Institute of Pharmacology and Toxicology, Leipziger Str. 44, D-39120 Magdeburg, Germany. axel.becker@med.ovgu.de
Grecksch
Gisela
G
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010208:Papaverine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018967:Risperidone / Q000494:pharmacology; D020889:Rolipram / Q000494:pharmacology
D014150:Antipsychotic Agents; D010726:Phosphodiesterase Inhibitors; D010208:Papaverine; D006220:Haloperidol; D020889:Rolipram; D018967:Risperidone