TCRM-4026-Casopitant: a novel NK1-receptor antagonist in
نویسندگان
چکیده
Correspondence: Christina Ruhlmann Odense University Hospital, Department of Oncology, Sdr. Boulevard 29, DK-5000 Odense C, Denmark Tel +45 6541 3834 email christina.ruhlmann@ouh. regionsyddanmark.dk Abstract: Chemotherapy-induced nausea and vomiting (CINV) are among the most feared and distressing symptoms experienced by patients with cancer. The knowledge of the pathogenesis and neuropharmacology of CINV has expanded enormously over the last decades, the most significant discoveries being the role of 5-hydroxytryptamine (5-HT) 3 and neurokinin (NK) 1 receptors in the emetic reflex arch. This has led to the development of two new classes of antiemetics acting as highly selective antagonists at one of these receptors. These drugs have had a huge impact in the protection from chemotherapy-induced vomiting, whereas the effect on nausea seems to be limited. The first NK 1 receptor antagonist, aprepitant, became clinically available in 2003, and casopitant, the second in this class of antiemetics, has now completed phase III trials. This review delineates the properties and clinical use of casopitant in the prevention of CINV.
منابع مشابه
Casopitant: a novel NK1-receptor antagonist in the prevention of chemotherapy-induced nausea and vomiting
Chemotherapy-induced nausea and vomiting (CINV) are among the most feared and distressing symptoms experienced by patients with cancer. The knowledge of the pathogenesis and neuropharmacology of CINV has expanded enormously over the last decades, the most significant discoveries being the role of 5-hydroxytryptamine (5-HT)(3)- and neurokinin (NK)(1) receptors in the emetic reflex arch. This has...
متن کامل(S)-1-[3,5-Bis(trifluoromethyl)phenyl]-N-methylethylamine–(R)-2-hydroxybutanedioic acid (1/1)
In the title compound, C(11)H(11)F(6)N·C(4)H(6)O(5), a key inter-mediate in the synthesis of the NK1 receptor antagonist of casopitant, the F atoms of the trifluoro-methyl groups are disordered over two sites with equal occupancies. In the crystal, the components are linked by bifurcated N-H⋯(O,O) hydrogen bonds.
متن کاملPharmacokinetics and brain penetration of casopitant, a potent and selective neurokinin-1 receptor antagonist, in the ferret.
The pharmacokinetics and brain penetration of the novel neurokinin (NK)-1 receptor antagonist casopitant [1-piperidinecarboxamide, 4-(4-acetyl-1-piperazinyl)-N-((1R)-1-(3,5-bis(trifluoromethyl)phenyl)ethyl)-2-(4-fluoro-2-methylphenyl)-N-methyl-, (2R,4S)-; GW679769] were examined in ferrets. The ferret is known to respond to the full spectrum of agents recognized to induce emesis in humans, and ...
متن کاملCasopitant and ondansetron for postoperative nausea and vomiting prevention in women at high risk for emesis: a phase 3 study.
HYPOTHESIS Postoperative nausea and vomiting (PONV) are associated with a variety of complications. Neurokinin subtype 1 receptor antagonists have antiemetic activity in the postoperative setting, and the neurokinin subtype 1 receptor antagonist casopitant mesylate (GW679769) was well tolerated and effective at reducing the incidence of PONV in phase 1 and phase 2 trials. DESIGN A multicenter...
متن کاملThe difficult trials.
addition of the NK1-receptor antagonist, casopitant (day 1–3), to a combination of ondansetron (day 1–3) plus dexamethasone (day 1) was investigated in patients receiving moderately emetogenic chemotherapy [4]. In a subpopulation (n = 123) treated with oxaliplatin-based chemotherapy, the 0–120-h complete response rate (no emesis and no need for rescue antiemetics) was improved from approximatel...
متن کامل