Antipsychotics and neuropeptides: the atypical profile of CI-943 and its relationship to neurotensin.
CI-943 is a new drug candidate with antipsychotic-like activity in a variety of behavioural tests in rodents and primates, but without any affinity for brain dopamine receptors. CI-943 does not cause dystonia in monkeys, a predictive symptom of extrapyramidal side effects (EPS). Its mechanism of action remains unclear. Neurotensin (NT) concentration in nucleus accumbens and caudate is increased by CI-943; this may be associated with its antipsychotic effect. Indeed various observations suggest that the clinical action of antipsychotic drugs may at least be partially mediated by some neuropeptides. Various actions of neurotensin are reviewed. The hypothesis on the role of neurotensin represents a new strategy in the development of pharmacological tools for the treatment of schizophrenia.
Liégeois
J F
JF
Department of Medicinal Chemistry, University of Liège, Belgium.
Bonaventure
P
P
Delarge
J
J
Damas
J
J
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D009479:Neuropeptides / Q000378:metabolism*; D009496:Neurotensin / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology*
D014150:Antipsychotic Agents; D007093:Imidazoles; D009479:Neuropeptides; D011743:Pyrimidines; D009496:Neurotensin; C061283:CI 943