Synthesis and smooth muscle-selective relaxant activity of a piperidine analogue: 1-(4'-fluorophenacyl)-4-hydroxy-4-phenyl-piperidinium chloride.

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% Cl) 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 microM), 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 microM) 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 receptor-operated Ca++ channels.