Effects of rimcazole, a specific antagonist of sigma sites, on the antitussive effects of non-narcotic antitussive drugs.
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.
Kamei
J
J
Department of Pharmacology, Faculty of Pharmacological Sciences, Hoshi University, Tokyo, Japan.
Iwamoto
Y
Y
Misawa
M
M
Kasuya
Y
Y
D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D003915:Dextromethorphan / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009665:Noscapine / Q000494:pharmacology*; D017480:Receptors, sigma / Q000037:antagonists & inhibitors*
D002227:Carbazoles; D017480:Receptors, sigma; D003915:Dextromethorphan; D009665:Noscapine; C034931:rimcazole