[mrsD]

There has been research for quite a while on this concept, and it looks like
perhaps we will see these soon.

Antidepressants in the Pipeline
Question

When do you think the antidepressants targeting NK-1/NK-2 receptors will be approved?
Expert Response from C. Lindsay DeVane, PharmD
Professor of Psychiatry and Vice Chair of Research, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina

Drugs that act as antagonists at neurokinin (NK) receptors have the potential to provide therapeutic benefits for a number of conditions. Evidence exists for the involvement of one or more NK receptors in the pathophysiology or modulation of stress, anxiety, depression, nausea, and bowel disorders.

The endogenous neurochemicals known as tachykinins were discovered over 70 years ago, but compounds that antagonize their action at specific receptors were only developed during the past decade. The tachykinins are products of 2 genes that code for substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). Three subtypes of NK receptors have been identified and designated as NK-1, NK-2, and NK-3.

The first NK receptor antagonist to be developed was an SP, NK-1 antagonist previously known as MK-869. It was initially shown to have therapeutic effects in a clinical trial of patients with mixed anxiety and depression. Subsequently, randomized controlled trials comparing it with paroxetine in depressed patients failed to substantiate its initial efficacy, and development shifted to its antinauseant effect. This drug, now known as aprepitant, was marketed in 2003 with the brand name of Emend for the prevention of nausea and vomiting in cancer patients undergoing chemotherapy. Despite the failure of MK-869 as an antidepressant, subsequent NK antagonists now in phase 2 or 3 of development appear likely to be marketed as antidepressants. Phase 2 involves testing a drug in 100 to 500 patients to gather evidence of efficacy and tolerability, while phase 3 testing represents the last hurdle before accumulated data from testing of 1000 to 5000 patients is submitted to the FDA for approval.

The premarketing development of saredutant, an NK-2 antagonist, is nearing completion by sanofi-aventis. There are indications from preclinical studies that NK-2 antagonists may have more consistent anxiolytic and antidepressant effects than SP or NK-1 antagonists. Data on the FDA Web site on April 9, 2007 (http://www.clinicaltrials.gov) indicated that several phase 3 clinical trials of saredutant are complete or nearly completed. These include randomized, double-blind, placebo-controlled studies in depression compared with placebo; discontinuation effects; comparison with escitalopram as an active control; and the treatment of generalized anxiety disorder. Given the time required for the FDA to review the comprehensive database submitted with a request for drug marketing, and to reach a decision, we can hope for the appearance of the first NK-2 antagonist with antidepressant properties in late 2007 or 2008.
Posted 04/24/2007
Suggested Readings

* Griebel G, Perrault G, Soubrie P. Effects of SR48968, a selective non-peptide NK2 receptor antagonist on emotional processes in rodents. Psychopharmacology. 2001;158:241-251.
* Herpfer I, Lieb K. Substance P receptor antagonists in psychiatry: rationale for development and therapeutic potential. CNS Drugs. 2005;19:275-294.
* Salome N, Stemmelin J, Cohen C, Griebel G. Selective blockade of NK2 or NK3 receptors produces anxiolytic and antidepressant-like effects in gerbils. Pharmacol Biochem Behav. 2006;83:533-539.
* Steinberg R, Alonso R, Griebel G, et al. Selective blockade of neurokinin-2 receptors produces antidepressant-like effects associated with reduced corticotropin-releasing factor function. J Pharm Exp Ther. 2001;299:449-458.

http://www.medscape.com/viewarticle/555557?src=mp

These look very promising to me...as they affect Substance P expression.
Substance P is elevated in chronic pain patients and also becomes elevated in the elderly. I myself would give these a try (and I do not expose myself to other types).

[fiberowendy2000]

Substance P is also major factors in Bipolar Disorder and Fibromyalgia. Sounds promising, but then again so has everything else I have heard of coming down the pike. Then they go on the market and poop out.
I will cross my fingers but I don't hold out hope.