Effect of noscapine, the antitussive opioid alkaloid, on bradykinin-induced smooth muscle contraction in the isolated ileum of the guinea-pig

Abstract

Bradykinin (BK) and related kinins are autocoid peptides that play integral roles in many pathophysiological processes such as cough. In this study, the inhibitory effect of noscapine, the antitussive opioid alkaloid, on BK receptors, was tested in the guinea-pig ileum. Contractions of the isolated ileum of the guinea-pig in response to BK were inhibited by noscapine (10-1,000 nM) in a concentration-dependent manner. Concentration-response curves (CRCs) to BK were slightly shifted to the right with a concomitant decrease in the maximum effect. A pA2 value of 6.68 was calculated for noscapine. The slope of the Schild plot of the antagonism was found to be 0.56. Noscapine had no effect on contractions induced by KCl, acetylcholine, histamine, 5-hydroxy tryptamine or angiotensin II. In conclusion, noscapine has a specific antagonistic effect on BK receptors and the mode of inhibition was found to be non-competitive.

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 mechanism of ACEI‐induced dry cough has been attributed to bradykinin accumulation and/or the increment of prostaglandin synthesis associated with the use of ACEI 4–7 . Recent work in our laboratory on the contractile effects of bradykinin on the guinea pig ileum has shown that noscapine, an isoquinoline alkaloid found in opium, 8 is a non‐competitive inhibitor of this peptide 9 . Unlike most other alkaloids obtained from the opium latex, this drug is devoid of any significant analgesic, sedative or euphoriant effects, which are commonly associated with this group of drugs.…”

Ovary Cells Apoptosis in Opium-Addicted Diabetic and Non-Diabetic Rats

“…Papaverine, another derivative of opium, is a vasodilator which is known to induce apoptosis in vascular endothelial and smooth muscle cells (15). Noscapine (one of the main components of opium) which serves as a tubulin-binding agent has also been demonstrated to activate micro-tubule dynamics to block mammalian cells mitosis through triggering of the c-Jun NH2-terminal kinase (JNK) pathway (11). It has been reported that C-Jun facilitates apoptosis of colorectal carcinoma P53 dependent pathway (10).…”

Chiral differentiation of the noscapine and hydrastine stereoisomers by electrospray ionization tandem mass spectrometry

“…Noscapine is an isoqiunoline alkaloid derived from opium. Noscapine has medical benefits, and it has been used as a natural antitussive agent for decades without any toxic effects. Furthermore, this alkaloid shows antitumor activity in various cancers like breast, lung and colon cancer .…”