Research Article

Synthesis and Pharmacological Screening of 1-(2`, b s4`-dimethoxyphenacyl)-4-hydroxy-4-phenylpiperidinium bromide

Syed I.H. Taqvi, Mohammad T. Aftab, Muhammad N. Ghayur, Anwar H. Gilani and Zafar S. Saify
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The intestinal and cardiovascular relaxant activities of a newly synthesized piperidine derivative: 1-(2`, s4`-dimethoxyphenacyl)-4-hydroxy-4-phenylpiperidinium bromide were studied in isolated tissue preparations. The test compound was prepared by dissolving 4-hydroxyphenylpiperidine and 1-(4-methylphenacyl) bromide in acetone. The test compound exhibited dose-dependent relaxant effect on the spontaneous and K+ (75 mM)-induced contractions of isolated rabbit jejunum with respective EC50 values of 0.31 mM (0.09-0.96, 95% CI) and 0.61 mM (0.38-0.99). The Ca++ Channel Blocking (CCB) activity was confirmed when the test compound (0.1-0.5 mM) shifted the Ca++ dose-response curves to the right, similar to that produced by verapamil (0.1-1.0 μM), a standard CCB. When tested in Langendorff perfused rabbit heart preparation, it exhibited a negative chronotropic effect in atria and ventricles with respective EC50 values of 0.28 mM (0.01-8.79) and 0.37 mM (0.01-9.01) and also a negative inotropic effect in atria and ventricles with respective EC50 values of 0.91 mM (0.04-17.69) and 2.77 mM (0.23-32.96). In the isolated rabbit aorta, the test compound showed a dose-dependent vasodilator effect on K+ (75 mM)-induced contractions and norepinephrine (1 μM) peak responses with EC50 values of 0.55 mM (0.24-1.26) and 0.22 mM (0.13-0.38), respectively. The results showed that inhibitory effects of the piperidine derivative on intestinal and cardiovascular preparations are mediated possibly via blockade of voltage and receptor-operated Ca++ channels.

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  How to cite this article:

Syed I.H. Taqvi, Mohammad T. Aftab, Muhammad N. Ghayur, Anwar H. Gilani and Zafar S. Saify, 2006. Synthesis and Pharmacological Screening of 1-(2`, b s4`-dimethoxyphenacyl)-4-hydroxy-4-phenylpiperidinium bromide . International Journal of Pharmacology, 2: 146-151.

DOI: 10.3923/ijp.2006.146.151



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