The NK1-receptor antagonist NKP608 has an antidepressant-like effect in the chronic mild stress model of depression in rats.
The chronic mild stress (CMS) model of depression was used to study the potential antidepressant-like activity of NKP608, a non-peptidic, specific, potent and orally active NK1 receptor antagonist. In this model, a substantial decrease in consumption of a 1% sucrose solution is observed in rats continously subjected to a variety of mild stressors. This effect can be reversed by chronic administration of various classes of antidepressant drugs. Chronic, oral treatment with NKP608 (once daily for 5 weeks) gradually reversed CMS-induced reductions in sucrose consumption and, the magnitude of this effect was comparable to that observed following administration of imipramine (10 mg/kg). The time-course of action of NKP608 in the CMS model was dose-dependent. At the dose of 0.03 mg/kg, NKP608 caused a full reversal of the CMS-induced deficit in sucrose consumption after 4 weeks of treatment (comparable to 5 weeks required for imipramine), while only 1 week of treatment was required in the group receiving the dose of 0.1 mg/kg NKP608. Lower (0.003 mg/kg) and higher (1.0 mg/kg) doses of the compound were ineffective. These results suggest that NKP608 has antidepressant-like properties in the CMS model in rats; the effect was comparable to conventional drugs, but the onset of action was faster than with the representative tricyclic antidepressant imipramine.
Papp
M
M
Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna St., 31-343, Krakow, Poland.
Vassout
A
A
Gentsch
C
C
D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D002908:Chronic Disease; D003863:Depression / Q000188:drug therapy* / Q000209:etiology*; D004597:Electroshock; D007099:Imipramine / Q000627:therapeutic use; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000627:therapeutic use*; D011804:Quinolines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000150:complications*
D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011804:Quinolines; C414491:quinoline-4-carboxylic acid (1-(3,5-bis-trifluoromethylbenzoyl)-2-(4-chlorobenzyl)piperidin-4-yl)amide; D007099:Imipramine