Interaction of noscapine with the bradykinin mediation of the cough response.
Angiotensin Converting Enzyme Inhibitors (ACEI) like captopril and enalapril, can induce persistant cough in man. Noscapine, an antitussive alkaloid, can be used to suppress ACEI-induced cough. Some workers have suggested a role for bradykinin in precipitation of ACE-induced cough. Work carried out in our laboratory has shown noscapine to be a non-competitive inhibitor of bradykinin in guinea pig ileum. It is therefore possible that noscapine suppresses cough by blocking the effect of bradykinin receptor activation in the airways. Guinea pigs were placed in a cough-chamber connected to an air pump and a pressure transducer. Capsaicin was sprayed into the chamber and cough was recorded as a distinctive change in air pressure inside the cough-chamber. Animals treated with 1 mg/kg captopril and enalapril for 7 days, showed increased cough response. Ten microgram/kg FR190997, a non-peptide agonist of the bradykinin B2 receptor, also increased the cough response. Noscapine at 0.5, 1 and 2 mg/kg was able to reverse the effects of ACEI and FR190997. Naloxone, a specific opioid receptor inhibitor, did not block the antitussive effects of noscapine in enalapril or FR190997 treated guinea pigs. This antitussive effect of noscapine is not mediated via the mu, kappa or delta opioid receptors. It is therefore possible that noscapine exerts its antitussive action by interfering with the bradykinin cough mediation.
Ebrahimi
S A
SA
Razi Institute for Drug Research, Iran University for Medical Sciences, Tehran, Iran.
Zareie
M R
MR
Rostami
P
P
Mahmoudian
M
M
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D001920:Bradykinin / Q000187:drug effects / Q000502:physiology*; D002211:Capsaicin; D002216:Captopril; D003371:Cough / Q000139:chemically induced / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004656:Enalapril; D006168:Guinea Pigs; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009665:Noscapine / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology; D043782:Receptor, Bradykinin B2 / Q000819:agonists / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D000996:Antitussive Agents; C107104:FR 190997; D009292:Narcotic Antagonists; D011804:Quinolines; D043782:Receptor, Bradykinin B2; D009270:Naloxone; D004656:Enalapril; D009665:Noscapine; D002216:Captopril; D002211:Capsaicin; D001920:Bradykinin