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Cardiovascular Effects of Noscapine, the Anti-Tussive Opioid Alkaloid

Background: Noscapine is a phtalideisoquinoline alkaloid with known anti-tussive properties. Recently, some other pharmacological effects and new potential clinical applications have been proposed for the drug. Since there is no data regarding its cardiovascular effects, cardiovascular actions of Noscapine were investigated in the present study. Methods: In this experimental study, the effects of cumulative concentrations of Noscapine on the vascular tone in rat isolated aorta and atrial rate and force of contraction in guinea pig isolated atria were evaluated using organ bath technique. Also, the Systolic Blood Pressure ( SBP) was assessed after administration of different single doses of Noscapine (0.5, 1, 2 and 3 mg/kg, i.p.) by tail-cuff method in rats. Moreover, in a randomized, double-blind, placebo-controlled crossover study, the effect of conventional anti-tussive dosage of Noscapine (15 mg, p.o., t.i.d) on the blood pressure and pulse rate of 24 healthy volunteers was assessed. For data analysis Student's t-test and ANOVA were used. Results: 1) High concentrations of Noscapine relaxed endothelium-lined rat aortic segments. Significant reduction in the dilatory response (%) of aortic segments was shown in the presence of Indomethacin (10 -5 M), a cyclooxygenase (COX) inhibitor, or L-NMMA (2×10 -4 M), a nitric oxide synthase (NOS) inhibitor, 2) Atrial contractility increased progressively with higher concentrations of Noscapine. Conversely, there was a trend for a decrease in spontaneous atrial contraction rate with the same concentrations of the drug, 3) No changes in SBP were demonstrated in rats receiving different doses of Noscapine and 4) Noscapine did not affect the blood pressure and pulse rate of healthy volunteers in both supine and upright positions. Conclusion: High concentrations of Noscapine caused a direct vasodilation, partly dependent to the COX and NO pathways in rat isolated aorta, and exerted positive inotropic and negative chronotropic effects in guinea pig isolated atria. Also, the drug did not affect the blood pressure either in healthy animal model or human volunteers, but further studies seems to be necessary to evaluate its effects in pathophysiological processes such as hypertension.