The tachykinins were first identified in 1931 however the therapeutic potential of their receptor antagonists is only starting to become realized. Tachykinin receptor antagonists have been implicated in various conditions such as depression/anxiety, pain, airway disease, incontinence, nausea and bowel disorder. Perhaps the big breakthrough in tachykinin therapeutics came in 1998 with the first demonstration that an NK-1 antagonist, MK-869, displays therapeutic activity in depressed patients. This was important not only for the development of tachykinin receptor antagonists but also for the treatment of depression. Affective disorders (including depression) and anxiety are amongst the 10 leading causes of disability in the US and other developed countries, affecting 9.5% and 15% of the US population respectively. Depressive disorders are therefore major contributors to the $40-55 billion global CNS therapeutics market. Treatments of depression are almost exclusively related to the modulation of monoamine neurotransmission and are commonly afflicted with tolerance or onset time related issues. Hence for the past decade the pharmaceutical industry has been seeking anti-depressant targets that involve novel mechanisms. This was one of the major reasons for the excitement surrounding MK-869. The same is true for angiotensin receptor ligands, which we have recently identified as candidate anti-depressants. Since the development of MK-869 a further 8 neurokinin receptor antagonists have entered the clinic. Likewise studies are underway in an attempt to optimize the therapeutic efficacy of this class. One issue is the question of which brain region(s) represent(s) the site of action of neurokinin receptor antagonist. This has been addressed by investigating NK-1 binding in various regions of the human brain. Tissue taken from subjects with depression showed decreased binding to NK-1 receptors across all cortical layers. To our knowledge this study represents only the second SP receptor binding study in humans with affective disorder and offers important information regarding the role of SP in psychiatric disease.

Entry date September, 2002

Adapted from Stockmeier et al Neuroreport 2002 Jul 2;13(9):1223-7

Interested in collaborating with this group? Contact leaddiscovery@bioportfolio.co.uk