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• W3149777908 startingPage "173" @default.
• W3149777908 abstract "This chapter is focused on the pharmacology of most relevant tachykinin NK1 receptor-selective compounds, with emphasis on the progress ofknowledge made possible by their use and on the therapeutic perspectives of these drugs. The first peptide antagonists of SP, synthesized about 20 years ago, were hampered by poor selectivity for NK1 receptors and other serious side effects. Since then the number of new compounds, peptidic at first and nonpeptidic later, being endowed with increasing potency and selectivity toward the NK1 receptor, has been growing continuously. A milestone in the field has been the introduction in 1991 of the first nonpeptide compound, CP96345, by Pfizer. CP96345 was instrumental, along with RP 67580 from Rhone-Poulenc, for recognition of the existence of species-related heterogeneity of NK1 receptors. CP96345 has been used in a plenty of preclinical studies aiming at investigating the pathophysiological role of the NK1 receptor, demonstrating the involvement of this receptor in pain perception and inflammation. The following compounds introduced in the field have been deprived of the undesired ion channel-blocking activity accompanying CP96345 and related compounds. By their use, the involvement of the NK1 receptor in emesis and in mediating affective disorders such as depression and anxiety has been proven. Antiemetic and antidepressive activity in humans has been reported first by CP122721 from Pfizer and by L754030 (MK869) from Merck, respectively. In contrast, disappointing results have been obtained with tachykinin NK1 antagonists tested as analgesics in patients affected by osteorathritis, neuropathic pain, dental pain and migraine, for reasons that are still not fully understood. Tachykinin NK1 receptor-selective antagonists are expected to provide therapeutic effects in peripheral inflammatory diseases such as asthma and inflammatory bowel disease. However, the first trials with these compounds in asthmatic patients have been negative." @default.
• W3149777908 created "2021-04-13" @default.
• W3149777908 creator A5007685909 @default.
• W3149777908 creator A5010124185 @default.
• W3149777908 date "2004-01-01" @default.
• W3149777908 modified "2023-10-01" @default.
• W3149777908 title "Tachykinin NK1 Receptor Antagonists" @default.
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