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        Synthesis and Smooth Muscle-Selective Relaxant Activity of a Piperidine Analogue: 1-(4'-Fluorophenacyl)-4-Hydroxy-4-Phenyl-Piperidinium Chloride

        Taqvi, Syed Intasar Hussain,Ghayur, Muhammad Nabeel,Gilani, Anwarul Hassan,Saify, Zafar Saeed,Aftab, Mohammad Tariq The Pharmaceutical Society of Korea 2006 Archives of Pharmacal Research Vol.29 No.1

        The antispasmodic and vasodilator activities of a newly synthesized piperidine derivative (1-(4'fluorophenacyl)-4-hydroxy-4-phenyl-piperidinium chloride) were studied in vitro. The test compound exhibited a dose-dependent relaxant effect on the spontaneous and $K^+$ (75 mM)-induced contractions of isolated rabbit jejunum with respective $EC_{50}$ values of 0.01 mM(0.01-0.02, 95% CI) and 0.30 mM (0.17-0.56). The $Ca^{++}$ channel blocking (CCB) activity was confirmed when the test compound (0.1-0.2 mM) shifted the $Ca^{++}$ dose-response curves to the right, similar to that produced by verapamil ($0.1-1.0{\mu}M$), a standard CCB. In the isolated rabbit aorta, the test compound showed a dose-dependent vasodilator effect on $K^+$ (75 mM)-induced contractions with an $EC_{50}$ value of 0.08 mM (0.02-0.26) while also suppressed the norepinephrine ($1{\mu}M$) control peak responses with $EC_{50}$ value of 0.08 mM (0.05-0.13, n=5). When tested in Langendorff perfused rabbit heart preparation, the test compound exhibited a negligible inhibitory effect on the rate or force of atrial and ventricular contractions when tested up to 5 mM. The results show smooth muscle-selective relaxant effect of the test compound on intestinal and vascular preparations mediated possibly via blockade of voltage and receptor-operated $Ca^{++}$ channels.

      • KCI등재

        Synthesis and Smooth Muscle-Selective Relaxant Activity of a Piperidine Analogue: 1-(4'-Fluorophenacyl)-4-Hydroxy-4-Phenyl-Piperidinium Chloride

        Syed Intasar Hussain Taqvi,Muhammad Nabeel Ghayur,Anwarul Hassan Gilani,Zafar Saeed Saify,Mohammad Tariq Aftab 대한약학회 2006 Archives of Pharmacal Research Vol.29 No.1

        The antispasmodic and vasodilator activities of a newly synthesized piperidine derivative (1-(4'- fluorophenacyl)-4-hydroxy-4-phenyl-piperidinium chloride) were studied in vitro. The test compound exhibited a dose-dependent relaxant effect on the spontaneous and K+ (75 mM)- induced contractions of isolated rabbit jejunum with respective EC50 values of 0.01 mM (0.01- 0.02, 95% CI) and 0.30 mM (0.17-0.56). The Ca++ channel blocking (CCB) activity was confirmed when the test compound (0.1-0.2 mM) shifted the Ca++ dose-response curves to the right, similar to that produced by verapamil (0.1-1.0 µM), a standard CCB. In the isolated rabbit aorta, the test compound showed a dose-dependent vasodilator effect on K+ (75 mM)- induced contractions with an EC50 value of 0.08 mM (0.02-0.26) while also suppressed the norepinephrine (1 µM) control peak responses with EC50 value of 0.08 mM (0.05-0.13, n=5). When tested in Langendorff perfused rabbit heart preparation, the test compound exhibited a negligible inhibitory effect on the rate or force of atrial and ventricular contractions when tested up to 5 mM. The results show smooth muscle-selective relaxant effect of the test compound on intestinal and vascular preparations mediated possibly via blockade of voltage and receptoroperated Ca++ channels.

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