• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.252-252
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• 1996

We Investigated the peripheral excitatory effect of capsaicin and KR-25018, a newly synthesized capsaicin derivative which was demonstrated to have a potent analgesic activity. KR-25018 and capsaicin were found to be both potent efficacious contractors of isolated guinea pig bronchial smooth muscle. KR-25018 was equipotent with capsaicin and [Sar$\^$9/,Met(O$_2$)$\^$11/]-substance P, 10-fold more potent than histamine and 10-fold less potent than (${\beta}$ -Ala$\^$8/)-neurokinin A(4-10), and their -log(M)EC$\_$50/ values were 6.94${\pm}$0.08, 6.86${\pm}$0.05, 6.96${\pm}$0.07, 5.64${\pm}$0.04, 7.96${\pm}$0.02, respectively. Contractile responses to KR-25018 and capsaicin were potentiated by phosphoramidon (1 ${\mu}$M), an inhibitor of neuropeptide-inactivating endopeptidase, but completely abolished in a calcium-free medium. These responses to KR-25018 and capsaicin were unaffected by the NK-1 antagonist CP96345 (1${\mu}$M), partially inhibited by the NK-2 antagonist SR48968 (1 ${\mu}$M) but almost completely abolished by a combination of the antagonists. A vanilloid receptor antagonist capsazepine competitively antagonized the responses to both KR-25018 and capsaicin (pA$_2$: aganst KR-25018, 5.98${\pm}$0.47; against capsaicin, 5.80${\pm}$0.31), and a capsaicin-sensitive cation channel antagonist ruthenium red caused significant reduction in the maximum responses to KR-25018 and capsaicin (pD'$_2$: against KR-25018, 4.61${\pm}$0.33; against capsaicin 4.96${\pm}$0.21). In conclusion, the present results suggest that KR-25018 and cpasaicin act on the same vanilloid receptor inducing the influx of calcium through ruthenium red-sensitive cation channel and produce contractile responses via the release of tachykinins that act on both NK-1 and NK-2 receptor subtypes.

• Korean Journal of Clinical Pharmacy
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• v.20 no.1
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• pp.17-23
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• 2010

Aprepitant is a substance P/neurokinin-1 (NK1)-receptor antagonist that was approved in 2003 for prevention of CINV. In addition, updated anti-emetic guidelines that include the aprepitant regimen have been published by NCCN and ASCO. However there is scarce clinical data in Korea. The prospective study was performed to evaluate the prevention of high dose cisplatin induced nausea and vomiting in all patients who started high-dose cisplatin-based chemotherapy at our hospital. We checked the nausea severity and vomiting episodes by calling patients within 4 to 5 days after chemotherapy. The retrospective study was performed to compare the prevention of CINV in solid tumor patients who switched their anti-emesis regimen from the standard regimen to the aprepitant regimen. In aprepitant regimen, aprepitant was added to the same anti-emetic regimen used during previous cycles. We checked the nausea, vomiting grades and adverse events in electronic medical records (EMR). In prospective study, 195 patients were included in the analysis. 88.2% of patients achieved a complete response (no emesis and no rescue therapy). In retrospective study, 54 patients were reviewed. With aprepitant regimen, nausea and vomiting grades were improved in 22 patients (40.7%) and in 9 patients (16.7%), respectively. Compared with standard regimen, addition of aprepitant provided superior prevention against CINV in Korean patients receiving highly emetogenic cisplatin-based chemotherapy. Moreover, aprepitant significantly prevented CINV in patients who received the standard regimen to prevent CINV in previous chemotherapy cycles.