Effect of neurokinin-1 receptor antagonists on serotoninergic, noradrenergic and hippocampal neurons: comparison with antidepressant drugs.
Neurokinin-1 (NK1) receptor antagonists have been reported to possess antidepressant and anxiolytic properties in controlled trials. Since antidepressant and anxiolytic drugs act mainly by enhancing serotonin (5-HT) and norepinephrine (NE) neurotransmission in forebrain areas, the main focus of the present review is to critically examine the electrophysiological effects of NK1 receptor antagonists on serotoninergic and noradrenergic neurons, and then hippocampal neurons. It is concluded that NK1 antagonists increase the firing and burst activity of 5-HT neurons, increase burst activity of NE neurons, and modulate postsynaptic transmission at the hippocampus level. Further research is needed in order to develop more selective ligands for the human NK1 receptor and to gain better knowledge of required brain penetration and optimal pharmacodynamic conditions for their use in patients.
Gobbi
Gabriella
G
Department of Psychiatry, Univ. de Montreal and McGill University, 1033, Av. des Pins Ouest, Montreal, Canada H3A 1A1. gabriella.gobbi@mcgill.ca
Blier
Pierre
P
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008024:Ligands; D008959:Models, Neurological; D064729:Neurokinin-1 Receptor Antagonists; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000037:antagonists & inhibitors* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D012701:Serotonin / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology
D000928:Antidepressive Agents; D007211:Indoles; D054833:Isoindoles; D008024:Ligands; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D018040:Receptors, Neurokinin-1; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D012701:Serotonin; D013373:Substance P; C032292:substance P (6-11); D011761:Pyrrolidonecarboxylic Acid; D009638:Norepinephrine