Substance P is thought to be one of the most important neurotransmitters and neuromodulators present in the brain. Its pharmacology and that of its preferred neurokinin 1 (NK1) receptor has been intimately linked to the pathophysiology of neurological and psychiatric disorders, namely nociception, migraine, asthma, nausea, inflammatory bowel syndrome, urinary incontinence, anxiety and depression. This wide therapeutic potential triggered efforts to identify appropriate NK1 receptor antagonists. To date, aprepitant (MK-869, an anti-emetic agent) remains the only NK1 receptor antagonist on the market. Numerous NK1 antagonists are in development, not only for prevention of nausea and vomiting, but also for treatment of overactive bladder and irritable bowel syndrome. Experimental data indicate a role of tachykinin NK2 receptors in the regulation of intestinal motor functions (both excitatory and inhibitory), secretions, inflammation and visceral sensitivity. Accordingly, selective NK2 receptor antagonists can reactivate inhibited motility or decrease inflammation- or stress-associated hypermotility. Thus, blockade of peripheral tachykinin NK2 receptors should be considered as a viable mechanism for decreasing the painful symptoms and altered bowel habits of irritable bowel syndrome patients. In fact, several projects are in preclinical and clinical development for treatment of irritable bowel syndrome.

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