Neurotensin agonists as an alternative to antipsychotics.
Neurotensin (NT) is a 13 amino acid neuropeptide that is found in the central nervous system and in the gastrointestinal tract. In brain, this peptide is prominently associated anatomically with dopaminergic, as well as other neurotransmitter systems. Based on animal studies, already decades old, researchers have hypothesised that NT receptor agonists will have antipsychotic properties in patients. However, to date no one has obtained a non-peptide NT receptor agonist. Therefore, there has been great interest in obtaining peptide analogues of NT, that, unlike NT resist degradation by peptidases and cross the blood-brain barrier, yet have the pharmacological characteristics of native NT, for therapeutic use in the treatment of schizophrenia, as well as other neuropsychiatric diseases such as Parkinson's disease and addiction to psychostimulants. In this review, we present the rationale for development of NT receptor agonists for treatment of certain central nervous system diseases, as well as a review of those peptide agonists that are in early stages of development.
Boules
Mona
M
Neuropsychopharmacology Laboratory and Nicotine Dependence Center, Mayo Foundation for Medical Education and Research, 4500 San Pablo Road, Jacksonville, FL 32224, USA.
Fredrickson
Paul
P
Richelson
Elliott
E
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001480:Basal Ganglia Diseases / Q000209:etiology; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D008253:Macaca mulatta; D009496:Neurotensin / Q000008:administration & dosage / Q000819:agonists* / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use; D011618:Psychotic Disorders / Q000188:drug therapy / Q000378:metabolism; D018028:Receptors, Neurotensin / Q000819:agonists*; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism
D014150:Antipsychotic Agents; D010446:Peptide Fragments; D018028:Receptors, Neurotensin; C407426:neurotensin 69L; D009496:Neurotensin