Substance P antagonists: meet the new drugs, same as the old drugs? Insights from transgenic animal models.
Antidepressants that primarily target the reuptake of monoamines have been highly successful treatments. However, therapies with these drugs still have several drawbacks, namely severe side effects, delays in the onset of action, and a significant percentage of non-responders. Recently, non-peptidic antagonists of the neurokinin 1 receptor, or substance P antagonists, have emerged as a novel class of drugs with antidepressant efficacy that is comparable to current drugs, but a potentially reduced side effect profile. This review summarizes the pre-clinical evidence derived from pharmacological and transgenic animal studies that suggests an important role for the substance P/neurokinin 1 system in anxiety and depression. Also, potential mechanisms by which substance P antagonists may produce their therapeutic effects are discussed.
Santarelli
Luca
L
Center for Neurobiology and Behavior, Columbia University, New York, New York 10032, USA. ls472@columbia.edu
Saxe
Michael D
MD
D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D002986:Clinical Trials as Topic; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D015507:Drugs, Investigational / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D013373:Substance P / Q000037:antagonists & inhibitors* / Q000502:physiology
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D015507:Drugs, Investigational; D018040:Receptors, Neurokinin-1; D013373:Substance P