Interaction of noscapine with the bradykinin mediation of the cough response

Abstract

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.

Noscapine suppresses angiotensin converting enzyme inhibitors‐induced cough

“…showed that FR190976 (a bradykinin agonist) similar to ACEI could potentiate cough reflexes. 10 The present study shows that noscapine, a bradykinin antagonist, could effectively suppress cough in patients treated with ACEI. 9 This further supports the involvement of bradykinin in ACEI-induced cough reflexes.…”

“…The only important and approved clinical effect of noscapine is its antitussive activity 8 . The experimental work with guinea pigs has shown that noscapine is very effective as an antitussive agent, 10 especially when cough is caused by bradykinin agonist FR190997 or ACEI, which inhibit the degradation of bradykinin 11 . The present work was carried out to investigate the effectiveness of noscapine in mitigating the dry cough induced by ACEI therapy.…”

Opium Poppy: Genetic Upgradation Through Intervention of Plant Breeding Techniques

“…In the treatment of cancers, noscapine appears to interfere with the functioning of microtubule and thus in division of cancer cells while in treatment of stroke patients, noscapine seems to block the bradykinine β-2 receptors which help in recovery from the disease. Early studies in the treatment of prostate cancer are very promising [21]. Scientists have found a noticeable decrease in mortality in patients treated with noscapine [22].…”

“…Papaverine is used in the treatment of spasms of the gastrointestinal tract, bile ducts and ureter. It is also used as a cerebral and coronary vasodilator in subarachnoid hemorrhage (combined with balloon angioplasty) and coronary artery bypass surgery [21,[23][24][25]. Papaverine is also used as an erectile dysfunction drug alone or sometimes in combination with phentolamine [26,27].…”

“…During microsurgery, papaverine is used as a smooth muscle relaxant and is directly applied to blood vessels [28,29]. It is also applied in cryopreservation of blood vessels along with other glycosaminoglycans and protein suspensions [21,30]. Papaverine also functions as a vasodilator during cryopreservation when used in conjunction with verapamil, phentolamine, nifedipine, tolazoline or nitroprusside [22,31].…”