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
 
Facebook Twitter Digg Reddit Linkedin StumbleUpon E-mail
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.
Services
Related Articles in ASCI
Search in Google Scholar
View Citation
Report Citation
 
  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

URL: https://scialert.net/abstract/?doi=ijp.2006.146.151

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.
    CrossRef  |  PubMed  |  Direct 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.
    CrossRef  |  PubMed  |  Direct 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.
    CrossRef  |  PubMed  |  Direct 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.
    PubMed  |  Direct Link  |  


  18. Godfraind, T., R. Miller and M. Wibo, 1986. Calcium antagonism and calcium entry blockade. Pharmacol. Rev., 38: 321-416.
    PubMed  |  Direct 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.
    PubMed  |  Direct 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  |  
©  2023 Science Alert. All Rights Reserved