Mental disorders are common in the United States and internationally. An estimated 22% of Americans ages 18 and older suffer from a diagnosable mental disorder in a given year translating to 44.3 million people. Affective disorders, including various anxiety and mood disorders and are amongst the 10 leading causes of disability in the US and other developed countries. Anxiety disorders are the most common mental illnesses and include panic disorder, phobias, extreme shyness, obsessive-compulsive behaviors, and generalized anxiety, which together disrupt the lives of an estimated 15% of the population. Depressive (mood) disorders are less common but often more debilitating and include major depression, bipolar disorder and dysthymic disorder. Perhaps most importantly, there is significant co-morbity amongst the various mental disorders and, for example, 50-60% of individuals with major depression report a lifetime history of one or more anxiety disorders. Classical antidepressants such as the TCAs and MAOIs are effective because they enhance either noradrenergic or serotonergic mechanisms, or both, however these therapeutic classes bring about numerous undesirable side effects. More recent developments such as SSRIs, norepinephrine reuptake inhibitors or molecules able to block the uptake of both serotonin and norepinephrine were designed to provide similar efficacy to that of the TCAs but with a higher safety and tolerability profile. The most recent developments in the antidepressant market are still limited to the modulation of monoamine activity and up until recently there has been limited mechanistic diversity. Furthermore despite the development of newer antidepressants undesirable side effects remain a problem as does the slow onset of activity. Furthermore, approximately 30% of the population do not respond to current therapies. An important new development has been the emergence of potential novel mechanisms of action beyond the monoaminergic synapse (click here for "Central Nervous System Report 2002" an analysis of future directions in the CNS therapeutics). Researchers from Synaptic Pharmaceutical Corporation have recently described a novel antagonist of one such target, the Melanin concentrating hormone MCH1 receptor. This molecule, SNAP-7941, produced effects similar to clinically used antidepressants and anxiolytics in three animal models of depression/anxiety: the rat forced-swim test, rat social interaction and guinea pig maternal-separation vocalization tests. Given these observations, an MCH1-R antagonist may offer novel approaches to depression and/or anxiety. A further condition that is receiving considerable attention is obesity. It is estimated that somewhere between 34 and 61 million people in the US are obese and in much of the developing world incidence is increasing by about 1% per year. Obesity increases the likelihood of death from all causes by 20%, and more specifically death from coronary artery disease and stroke are increased by 25% and 10% respectively. The therapeutic market for obesity is relatively unmet and therefore offers considerable opportunities to companies with a focus on this condition. It is of considerable interest therefore that in addition to being anxiolytic/antidepressent, SNAP-7941 inhibited food intake stimulated by central administration of MCH, reduced consumption of palatable food, and, after chronic administration to rats with diet-induced obesity, resulted in a marked, sustained decrease in body weight. SNAP-7941, and MCH1 receptor antagonists in general therefore appear to represent a highly exciting advance in therapeutics.

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