Involvement of haloperidol-sensitive sigma-sites in antitussive effects.
The effects of selective sigma-ligands on the capsaicin-induced cough reflex in rats were studied. Intraperitoneal injection of (+)-N-allylnormetazocine ((+)-SKF-10,047) and N,N'-di(ortho-tolyl)guanidine (DTG) in doses that ranged from 0.3 to 3.0 mg/kg decreased the number of coughs dose dependently. The antitussive effects of these sigma-ligands were significantly attenuated by pretreatment with haloperidol. Pretreatment with haloperidol also markedly reduced the antitussive effects of (+/-)-pentazocine and dextromethorphan. These results suggest that haloperidol-sensitive sigma-sites may be involved in the regulation of coughs.
Kamei
J
J
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
Iwamoto
Y
Y
Kawashima
N
N
Hitosugi
H
H
Misawa
M
M
Kasuya
Y
Y
D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D002211:Capsaicin; D003371:Cough / Q000139:chemically induced / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006146:Guanidines / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D010620:Phenazocine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000187:drug effects*; D013237:Stereoisomerism
D000996:Antitussive Agents; D006146:Guanidines; D017480:Receptors, sigma; C012134:SK&F 10047; D010620:Phenazocine; D006220:Haloperidol; C050232:1,3-ditolylguanidine; D002211:Capsaicin