Kamei J, Iwamoto Y, Misawa M, Kasuya Y
Department of Pharmacology, Faculty of Pharmacological Sciences, Hoshi University, Tokyo, Japan.
Eur J Pharmacol. 1993 Sep 28;242(2):209-11. doi: 10.1016/0014-2999(93)90083-t.
We examined the effects of rimcazole, a specific antagonist of sigma sites, on the antitussive effects of dextromethorphan and noscapine in mice. Intraperitoneal injection of rimcazole, in doses from 1 to 10 mg/kg, significantly and dose dependently antagonized the cough depressant effect of N,N'-di(orthotolyl)guanidine (DTG), a sigma ligand. The cough depressant effects of dextromethorphan (3 mg/kg i.p.) and noscapine (10 mg/kg i.p.) were also significantly and dose dependently reduced by pretreatment with rimcazole. However, rimcazole (10 mg/kg i.p.) did not have a significant effect on the antitussive effect of morphine (3 mg/kg i.p.). Furthermore, rimcazole by itself (10 and 30 mg/kg i.p.) had no significant effect on the number of coughs. These results suggest that sigma sites may be involved in the antitussive mechanism of centrally acting non-narcotic antitussive drugs.
我们研究了西格玛位点特异性拮抗剂利姆卡唑对右美沙芬和那可丁在小鼠体内镇咳作用的影响。腹腔注射剂量为1至10mg/kg的利姆卡唑，可显著且剂量依赖性地拮抗西格玛配体N，N'-二（邻甲苯基）胍（DTG）的镇咳作用。利姆卡唑预处理也可显著且剂量依赖性地降低右美沙芬（腹腔注射3mg/kg）和那可丁（腹腔注射10mg/kg）的镇咳作用。然而，利姆卡唑（腹腔注射10mg/kg）对吗啡（腹腔注射3mg/kg）的镇咳作用没有显著影响。此外，利姆卡唑本身（腹腔注射10和30mg/kg）对咳嗽次数没有显著影响。这些结果表明，西格玛位点可能参与中枢性非麻醉性镇咳药物的镇咳机制。
