Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 346, Issue 3, pp 339–344 | Cite as

Effects of the novel calcium channel blocker, anipamil, on the isolated rabbit heart

Comparison with verapamil and gallopamil
  • Riccardo Raddino
  • Enzo Poli
  • Evasio Pasini
  • Roberto Ferrari


The calcium channel blocking activity of the novel phenylalkylamine derivative, anipamil, was tested on the isolated rabbit heart, in comparison with verapamil and gallopamil. Anipamil and the other calcium channel blockers lower left ventricular pressure in the same concentration range (10−8 –10−4 mol/1). The negative inotropic effect of anipamil is only partially reversed (nearly 65%) by rising calcium concentration in the perfusion fluid, whilst a complete recovery is observed for verapamil and gallopamil. The negative inotropic effect of anipamil is of rapid onset but long lasting, being still present 12 h after washout. On the contrary, that of gallopamil or verapamil completely disappears within 3 h of washout.

Verapamil and gallopamil (10−8 –10−4 mol/1) depress spontaneous heart rate up to asystolia and abolish the vasopressin- and Bay K 8644-induced coronary spasm. Anipamil, on the contrary, does not modify coronary spasm elicited by both stimulants and spontaneous heart rate up to 10−4 mol/l.

These observations suggest that anipamil, in the isolated rabbit heart, possesses a peculiar pharmacological profile, since its calcium channel blocking activity is confined to the myocardial muscle.

Key words

Anipamil Verapamil Gallopamil Calcium channels Isolated rabbit heart 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bayer R, Kalusche D, Kaufmann R, Mannhold R (1975) Inotropic and electrophysiological actions of verapamil and D-600 in mammalian myocardium. III. Effects of the optical isomers on transmembrane action potentials. Naunyn-Schmiedeberg's Arch Pharmacol 290:81–97Google Scholar
  2. Brezinski ME, Darius H, Lefer AM (1986) Cardioprotective actions of a new calcium channel blocker in acute myocardial ischemia. Arzneimittelforschung 36:464–466Google Scholar
  3. Bristow MR, Green RD (1977) Effect of diazoxide, verapamil and compound D-600 on isoproterenol and calcium-mediated dose-response relationships. Eur J Pharmacol 45:267–279Google Scholar
  4. Broadley KJ (1979) The Langendorff heart preparation. Reappraisal of its role as a research and teaching model for coronary vasoactive drugs. J Pharmacol Methods 2:143–152Google Scholar
  5. Curtis MJ, Walker MJ, Yuswack T (1986) Actions of the verapamil analogues, anipamil and ronipamil, against ischaemia-induced arrhythmias in conscious rats. Br J Pharmacol 88:355–361Google Scholar
  6. Denniss AR, Kingma JG Jr, Hearse DJ, Downey JM, Yellon DM (1990) Long acting calcium antagonist anipamil limits myocardial necrosis and penetrates the ischaemic zone during 24 h of coronary artery occlusion in the dog. Can J Cardiol 6:31–37Google Scholar
  7. Dies R, Schneider G, Hahn KJ (1989) Antihypertensive efficacy of anipamil in mild to moderate hypertension. J Cardiovasc Pharmacol 13 [Suppl 4]:S76-S78Google Scholar
  8. Dillon JS, Nayler WG (1988) The Ca2+-antagonist and binding properties of the phenylalkylamine, anipamil. Br J Pharmacol 94:253–263Google Scholar
  9. Ferrari R, Raddino R, Ceconi C, Curello S, Ghielmi S, Visioli O (1989) Prolonged protective effect of the calcium antagonist anipamil on the ischemic reperfused rabbit myocardium: comparison with verapamil. Cardiovasc Drugs Ther 3:403–412Google Scholar
  10. Ferrari R, Boraso A, Cargnoni A, Pasini E, Raddino R,Albertini A (1990) Effects of anipamil on myocardial sarcolemmal and mitochondrial calcium transport, comparison with verapamil and nifedipine. Eur J Pharmacol - Mol Pharmacol Sect 189:149–161Google Scholar
  11. Fleckenstein A (1977) Specific pharmacology of calcium in myocardium, cardiac pacemakers, and vascular smooth muscle. Ann Rev Pharmacol Toxicol 17:149–166Google Scholar
  12. Fleckenstein-Grain G, Frey M, Fleckenstein A (1984) Calcium antagonists: mechanisms and therapeutic uses. TIPS 5:283–286Google Scholar
  13. Frey M, Zorn J, Fleckenstein-Grun G, Fleckenstein A (1989) Antihypertensive, anticalcinotic, and antiarteriosclerotic properties of anipamil, a long-acting new derivative of verapamil. J Cardiovasc Pharmacol 13 [Suppl4]:S23-S28Google Scholar
  14. Galizzi JP, Qar J, Fosset M, Van Renterghem C, Lazdunski M (1987) Regulation of calcium channels in aortic muscle cells by protein kinase C activators (diacylglycerol and phorbol esters) and by peptides (vasopressin and bombesin) that stimulate phosphoinositide breakdown. J Biol Chem 262:6947–6950Google Scholar
  15. Glossman H, Ferry DR, Lübbecke F, Mewes R, Hofman F (1982) Calcium channels: direct identification with radioligand binding studies. TIPS 3:431–437Google Scholar
  16. Guerrero JR, Martin SS (1984) Verapamil: full spectrum calcium channel blocking agent: an overview. Med Res Rev 4:87–109Google Scholar
  17. Henry PD (1980) Comparative pharmacology of calcium antagonists: nifedipine, verapamil and diltiazem. Am J Cardiol 46:1047–1058Google Scholar
  18. Janis RA, Scriabine A (1983) Sites of action of Ca2+ channel inhibitors. Biochem Pharmacol 32:3499–3507Google Scholar
  19. Mac Leod BA, Moult M, Saint KM, Walker MJA (1989) The antiarrhythmic efficacy of intravenous anipamil against occlusion and reperfusion arrhythmias. Br J Pharmacol 98:1165–1171Google Scholar
  20. Mattiazzi AR, Garay A (1983) Negative inotropic effect of verapamil, nifedipine and phenylamine and its reversal by calcium or isoproterenol. Arch Int Physiol Biochim 91:133–144Google Scholar
  21. Nayler WG (1988) Ion-conducting channels: calcium. In: Nayler WG (ed) Calcium antagonists. Academic Press, London, pp 23–44Google Scholar
  22. Opie LH (1988) Calcium channel antagonists. Part V: second-generation agents. Cardiovasc Drugs Ther 2:191–203Google Scholar
  23. Raddino R, Manca C, Poli E, Bolognesi R, Visioli O (1986) Effects of 17 β-estradiol on the isolated rabbit heart. Arch Int Pharmacodyn Thér 281:57–65Google Scholar
  24. Raddino R, Poli E, Pelà G, Manca C (1989) Action of steroid sex hormones on the isolated rabbit heart. Pharmacology 38:185–190Google Scholar
  25. Raschack M (1984) Anipamil, a novel calcium antagonist with long lasting oral efficacy, as assessed against hypoxic and ischaemic damage of heart and kidney. International Symposium on Calcium Entry Blockers and Tissue Protection, Rome, March 15–16, p 34 (abstr)Google Scholar
  26. Tabrizchi R, Pang CCY, Walker MJA (1989) Effect of anipamil on cardiovascular status and regional blood flow in anaesthetized rats. Br J Pharmacol 98:1185–1190Google Scholar
  27. Thomas G, Chung M, Cohen CJ (1985) A dihydropyridine (Bay K 8644) that enhances calcium currents in guinea pig and calf myocardial cells. Circ Res 56:87–96Google Scholar
  28. Van Rossum JM (1963) Cumulative dose-response curves. Techniques for making the dose-response curves in isolated organs and the evaluation of drug parameters. Arch Int Pharmacody Ther 143:299–330Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Riccardo Raddino
    • 1
  • Enzo Poli
    • 2
  • Evasio Pasini
    • 1
  • Roberto Ferrari
    • 1
  1. 1.Department of CardiologyUniversity of BresciaBresciaItaly
  2. 2.Institute of PharmacologyUniversity of ParmaParmaItaly

Personalised recommendations