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International Journal of Pharmacology

Year: 2006 | Volume: 2 | Issue: 1 | Page No.: 146-151
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ABSTRACT

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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REFERENCES

  1. Saify, Z.S. and D.J. Haleem, 1994. Studies on the effect of 4-hydroxy-4-phenylpiperidine derivative (4HPPD) on mice brain dopamine metabolism. Int. Symp. Biochem. Biophys., 1: 36-39.
  2. Saify, Z.S., N. Mushtaq, K.M. Khan, S. Perveen and S.T. Shah et al., 2005. Synthesis and pharmacological activity of 4-4'-chlorophenyl-4-hydroxypiperidine derivatives. Chem. Pharm. Bull., 53: 64-66.
    Direct Link
  3. Saeed, M., Z.S. Saify, A.H. Gilani and Z. Iqbal, 1998. Studies on the effects of piperidine derivatives on blood pressure and smooth muscles contractions. Arch. Pharm. Res., 21: 370-373.
    CrossRefPubMedDirect Link
  4. McCarlin, P.P. and J. Butterworth, 2000. Bupivacaine suppresses Ca2+i oscillations in neonatal rat cardiomyocytes with increased extracellular K+ and is reversed with increased extracellular Mg2+. Anesth. Analg., 91: 82-88.
    Direct Link
  5. Hanouz, J.L., A. Yuon, G. Guesne, C. Eustratiades and G. Babatasi et al., 2001. The in vitro effects of renifentanil, sufentanil, fentanyl and alfentanil on isolated human right atria. Anesth. Analg., 93: 543-549.
    Direct Link
  6. Annoura, H., K. Nakainshi, M. Useugi, A. Fukunaga and S. Imajo et al., 2002. Synthesis and biological evaluation of new 4-arylpiperidine and 4-arylpiperidinols: Dual Na+ and Ca2+ channel blockers with reduced affinity for dopamine D2 receptors. Bioorg. Med. Chem., 10: 371-383.
    Direct Link
  7. Ziang, X., C. Cao, L. Wang, Y. Ding and Q. Xia, 2003. Negative inotropic effect of meperidine in rat ventricular muscle and the underlying mechanism. Acta Physiol. Sin., 55: 197-200.
    Direct Link
  8. Huang, Z.Q., G.G. Shi, J.H. Zheng and B. Liu, 2003. Effects of N-n-butylhaloparidol iodide on rat myocardial ischemia and reperfusion injury and L-type calcium current. Acta Pharmacol. Sin., 24: 757-763.
  9. North, R.A., 1986. Opioid receptor types and membrane ion channels. Trends Neurosci., 11: 114-117.
  10. NRC, 1996. Guide for the Care and Use of Laboratory Animals. National Academy Press, Washington, DC., USA., ISBN-10: 0309053773, Pages: 140.
    Direct Link
  11. Anwar-ul, S., H. Gilani and L. B. Cobbin, 1986. The cardio-selectivity of himbacine: A muscarine receptor antagonist. Naunyn-Schmiedebergs Arch. Pharmacol., 332: 16-20.
    CrossRefPubMedDirect Link
  12. Farre, A.J., M. Colombo, M. Fort and B. Gutierrez, 1991. Differential effects of various Ca2+ antagonists. Gen. Pharmacol.: Vasc. Syst., 22: 177-181.
    CrossRefPubMedDirect Link
  13. Van Rossum, J.M., 1963. Cumulative dose-response curves. II. Technique for the making of dose-response curves in isolated organs and the evaluation of drug parameters. Arch. Pharmacodyn. Therapie, 143: 299-330.
    PubMed
  14. Bolton, T.B., 1979. Mechanism of action of transmitter and other substances on smooth muscles. Physiol. Rev., 59: 606-718.
    PubMed
  15. McLeod, L.J., 1970. Pharmacological Experiments on Intact Preparation. 2nd Edn., Churchill Livingston, Edinburgh, London and New York, pp: 113.
  16. Karaki, H. and G. Weiss, 1988. Mini-review: Calcium release in smooth muscles. Life Sci., 42: 111-122.
  17. Godfraind, T., 1987. Classification of calcium antagonists. Am. J. Cardiol., 59: 11-23.
    PubMedDirect Link
  18. Godfraind, T., R. Miller and M. Wibo, 1986. Calcium antagonism and calcium entry blockade. Pharmacol. Rev., 38: 321-416.
    PubMedDirect Link
  19. Triggle, D.J., 1992. Drugs Affecting Calcium Regulation and Actions. In: Textbook of Pharmacology, Smith, G.M. and A.M. Reynard (Eds.). W.B. Saunders Co., Philadelphia, pp: 453-479.
  20. Hernnadez-Hernandez, R., M. Velasco, M. Armas-Hernandez, M.C. Armas-Padilla, 2002. Update on the use of calcium antagonists on hypertension. J. Hum. Hypertens, 16: 114-117.
    Direct Link
  21. Malecot, H. and W. Trautwein, 1987. On the relationship between Vmax of slow responses and Ca++-current availability in whole-cell clamped guinea-pig heart cell. Pflugers Arch., 410: 15-22.
    PubMedDirect Link
  22. Fleckenstein, A., 1977. Specific pharmacology of calcium in myocardium, cardiac pacemakers and vascular smooth muscle. Annu. Rev. Pharmacol. Toxicol., 17: 149-166.
    CrossRef
  23. Conti, C.R., C.J. Pepine, R.L. Feldman and J.A. Hill, 1985. Calcium antagonists. Cardiology, 72: 297-321.
  24. Clark, R.D., J.M. Caroon, A.F. Kluge, D.B. Repke and A.P. Roszkowski et al., 1983. Synthesis and antihypertensive activity of 4'-substituted spiro 4H-3,1-benzoxazine-4,4'-piperidin-2(1H)-ones. J. Med. Chem., 26: 657-661.
    Direct Link
  25. Takai, H., H. Obase, M. Teranishi, A. Karasawa and K. Kubo et al., 1985. Spiropiperidines. I. Synthesis of 1'-substituted spiro 4H-3,1-benzoxazine-4,4'-piperidin-2(1H)-one derivatives and evaluation of their antihypertensive activity. Chem. Pharm. Bull., 33: 1129-1139.
    Direct Link

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