Peripheral tachykinin receptors as potential therapeutic targets in visceral diseases.
More than 10 years of intensive preclinical investigation of selective tachykinin (TK) receptor antagonists has provided a rationale to the speculation that peripheral neurokinin (NK)-1, -2 and -3 receptors may be involved in the pathophysiology of various human diseases at the visceral level. In the airways, despite promising effects in animal models of asthma, pilot clinical trials with selective NK-1 or -2 receptor antagonists in asthmatics have been ambiguous, whereas the potential antitussive effects of NK-1, -2 or -3 antagonists have not yet been verified in humans. In the gastrointestinal (GI) tract, irritable bowel syndrome (IBS) and pancreatitis are appealing targets for peripherally-acting NK-1 and -2 antagonists, respectively. In the genito-urinary tract, NK-1 receptor antagonists could offer some protection against nephrotoxicity and cytotoxicity induced by chemotherapeutic agents, whereas NK-2 receptor antagonists appear to be promising new agents for the treatment of neurogenic bladder hyperreflexia. Finally, there is preclinical evidence for hypothesising an effect of NK-3 receptor antagonists on the cardiovascular disturbance that characterises pre-eclampsia. Other more speculative applications are also mentioned.
Lecci
Alessandro
A
Pharmacology Department of Menarini Ricerche, via Rismondo 12/A, 50131 Florence, Italy. alecci@menarini-ricerche.it
Maggi
Carlo Alberto
CA
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D005260:Female; D005765:Gastrointestinal Agents / Q000494:pharmacology / Q000627:therapeutic use; D005767:Gastrointestinal Diseases / Q000188:drug therapy / Q000503:physiopathology; D006168:Guinea Pigs; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011225:Pre-Eclampsia / Q000188:drug therapy / Q000503:physiopathology; D011247:Pregnancy; D051381:Rats; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors*; D015320:Tachykinins / Q000037:antagonists & inhibitors / Q000502:physiology; D014555:Urination Disorders / Q000188:drug therapy / Q000503:physiopathology
D018927:Anti-Asthmatic Agents; D019380:Anti-HIV Agents; D005765:Gastrointestinal Agents; D018039:Receptors, Tachykinin; D015320:Tachykinins