Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1984 May;73(5):1291–1296. doi: 10.1172/JCI111331

Effective treatment of verapamil intoxication with 4-aminopyridine in the cat.

S Agoston, E Maestrone, E J van Hezik, J M Ket, M C Houwertjes, D R Uges
PMCID: PMC425150  PMID: 6538884

Abstract

To study the value of 4-aminopyridine as an antidote to verapamil intoxication, we subjected 12 adult cats to verapamil poisoning by administering doses of 4.0-25.0 mg/kg verapamil by intravenous infusion. Six animals were given 4-aminopyridine 2 X 0.5 mg/kg i.v. after the verapamil infusion was stopped and the other six animals (the control group) were not. Verapamil caused profound cardiovascular depression and also partial neuromuscular block, both of which were completely reversed by 4-aminopyridine within 50 min, in spite of extremely high serum verapamil concentrations (ranging between 3,700 and 13,500 ng/ml). The six animals that received 4-aminopyridine survived the verapamil intoxication, whereas four of the six animals in the control group died. The results suggest that 4-aminopyridine may be useful in the treatment of verapamil intoxication.

Full text

PDF
1296

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Agoston S., Bowman W. C., Houwertjes M. C., Rodger I. W., Savage A. O. Direct action of 4-aminopyridine on the contractility of a fast-contracting muscle in the cat. Clin Exp Pharmacol Physiol. 1982 Jan-Feb;9(1):21–34. doi: 10.1111/j.1440-1681.1982.tb00775.x. [DOI] [PubMed] [Google Scholar]
  2. Al-Haboubi H. A., Bowman W. C., Houston J., Savage A. O. Effects of 4-aminopyridine on the isolated parasympathetically-innervated oesophagus of the domestic fowl chick. J Pharm Pharmacol. 1978 Aug;30(8):517–518. doi: 10.1111/j.2042-7158.1978.tb13309.x. [DOI] [PubMed] [Google Scholar]
  3. Bowman W. C., Savage A. O. Pharmacological actions of aminopyridines and related compounds. Rev Pure Appl Pharmacol Sci. 1981 Oct-Dec;2(4):317–371. [PubMed] [Google Scholar]
  4. Eichelbaum M., Birkel P., Grube E., Gütgemann U., Somogyi A. Effects of verapamil on P-R-intervals in relation to verapamil plasma levels following single I.V. and oral administration and during chronic treatment. Klin Wochenschr. 1980 Sep 15;58(18):919–925. doi: 10.1007/BF01477049. [DOI] [PubMed] [Google Scholar]
  5. Fleckenstein A. Specific pharmacology of calcium in myocardium, cardiac pacemakers, and vascular smooth muscle. Annu Rev Pharmacol Toxicol. 1977;17:149–166. doi: 10.1146/annurev.pa.17.040177.001053. [DOI] [PubMed] [Google Scholar]
  6. Folgering H., Rutten J., Agoston S. Stimulation of phrenic nerve activity by an acetylcholine releasing drug: 4-aminopyridine. Pflugers Arch. 1979 Mar 16;379(2):181–185. doi: 10.1007/BF00586945. [DOI] [PubMed] [Google Scholar]
  7. Gelbke H. P., Schlicht H. J., Schmidt G. Fatal poisoning with verapamil. Arch Toxicol. 1977 Jun 18;37(2):89–94. doi: 10.1007/BF00293857. [DOI] [PubMed] [Google Scholar]
  8. Hattori V. T., Mandel W. J., Peter D. Calcium for myocardial depression from verapamil. N Engl J Med. 1982 Jan 28;306(4):238–238. doi: 10.1056/nejm198201283060413. [DOI] [PubMed] [Google Scholar]
  9. Illes P., Thesleff S. 4-Aminopyridine and evoked transmitter release from motor nerve endings. Br J Pharmacol. 1978 Dec;64(4):623–629. doi: 10.1111/j.1476-5381.1978.tb17325.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Immonen P., Linkola A., Waris E. Three cases of severe verapamil poisoning. Int J Cardiol. 1981;1(1):101–105. doi: 10.1016/0167-5273(81)90056-5. [DOI] [PubMed] [Google Scholar]
  11. Johns A., Golko D. S., Lauzon P. A., Paton D. M. The potentiating effects of 4-aminopyridine on adrenergic transmission in the rabbit vas deferens. Eur J Pharmacol. 1976 Jul;38(1):71–78. doi: 10.1016/0014-2999(76)90202-8. [DOI] [PubMed] [Google Scholar]
  12. Katz B., Miledi R. Modification of transmitter release by electrical interference with motor nerve endings. Proc R Soc Lond B Biol Sci. 1967 Jan 31;167(1006):1–7. doi: 10.1098/rspb.1967.0008. [DOI] [PubMed] [Google Scholar]
  13. Katz B., Miledi R. The release of acetylcholine from nerve endings by graded electric pulses. Proc R Soc Lond B Biol Sci. 1967 Jan 31;167(1006):23–38. doi: 10.1098/rspb.1967.0011. [DOI] [PubMed] [Google Scholar]
  14. Kirpekar M., Kirpekar S. M., Prat J. C. Effect of 4-aminopyridine on release of noradrenaline from the perfused cat spleen by nerve stimulation. J Physiol. 1977 Nov;272(3):517–528. doi: 10.1113/jphysiol.1977.sp012057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kraynack B. J., Lawson N. W., Gintautas J. Neuromuscular blocking action of verapamil in cats. Can Anaesth Soc J. 1983 May;30(3 Pt 1):242–247. doi: 10.1007/BF03013802. [DOI] [PubMed] [Google Scholar]
  16. Leander S., Arner A., Johansson B. Effects of 4-aminopyridine on mechanical activity and noradrenaline release in the rat portal vein in vitro. Eur J Pharmacol. 1977 Dec 15;46(4):351–361. doi: 10.1016/0014-2999(77)90229-1. [DOI] [PubMed] [Google Scholar]
  17. Lundh H., Thesleff S. The mode of action of 4-aminopyridine and guanidine on transmitter release from motor nerve terminals. Eur J Pharmacol. 1977 Apr 21;42(4):411–412. doi: 10.1016/0014-2999(77)90176-5. [DOI] [PubMed] [Google Scholar]
  18. Molgó J. Voltage-clamp analysis of the sodium and potassium currents in skeletal muscle fibres treated with 4-aminopyridine. Experientia. 1978 Oct 15;34(10):1275–1279. doi: 10.1007/BF01981414. [DOI] [PubMed] [Google Scholar]
  19. Perkins C. M. Serious verapamil poisoning: treatment with intravenous calcium gluconate. Br Med J. 1978 Oct 21;2(6145):1127–1127. doi: 10.1136/bmj.2.6145.1127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Russell J. T., Thorn N. A. Calcium and stimulus-secretion coupling in the neurohypophysis. II. Effects of lanthanum, a verapamil analogue (D600) and prenylamine on 45-calcium transport and vasopressin release in isolated rat neurohypophyses. Acta Endocrinol (Copenh) 1974 Jul;76(3):471–487. [PubMed] [Google Scholar]
  21. Sand O., Haug E., Gautvik K. M. Effects of thyroliberin and 4-aminopyridine on action potentials and prolactin release and synthesis in rat pituitary cells in culture. Acta Physiol Scand. 1980 Mar;108(3):247–252. doi: 10.1111/j.1748-1716.1980.tb06530.x. [DOI] [PubMed] [Google Scholar]
  22. Stoyanov E., Vulchev P., Shturbova M., Marinova M. Clinical electromyomechanographic and electromyographic studies in decurarization with pymadine. Anaesth Resusc Intensive Ther. 1976 Apr-Jun;4(2):139–142. [PubMed] [Google Scholar]
  23. Uges D. R., Huizinga T. 4-aminopyridine; analysis of the substance and a method for the preparation of a solution for injection in man. Pharm Acta Helv. 1981;56(6):158–162. [PubMed] [Google Scholar]
  24. Uges D. R., Sohn Y. J., Greijdanus B., Scaf A. H., Agoston S. 4-Aminopyridine kinetics. Clin Pharmacol Ther. 1982 May;31(5):587–593. doi: 10.1038/clpt.1982.82. [DOI] [PubMed] [Google Scholar]
  25. Uges D. R., Versluis A., Ket J. M., Wesseling H. 4-Aminopyridine tablets; a method for the preparation. In-vitro and in-vivo studies. Pharm Acta Helv. 1982;57(4):122–128. [PubMed] [Google Scholar]
  26. Vizi E. S., van Dijk J., Foldes F. F. The effect of 4-aminopyridine on acetylcholine release. J Neural Transm. 1977;41(4):265–274. doi: 10.1007/BF01252021. [DOI] [PubMed] [Google Scholar]
  27. Wesseling H., Houwertjes M. C., de Langen C. D., Kingma J. H. Hemodynamic effects of high dosages of verapamil and the lack of protection by 4-aminopyridine in the rabbit. Arch Int Pharmacodyn Ther. 1983 Nov;266(1):106–112. [PubMed] [Google Scholar]
  28. Woie L., Storstein L. Successful treatment of suicidal verapamil poisoning with calcium gluconate. Eur Heart J. 1981 Jun;2(3):239–242. doi: 10.1093/oxfordjournals.eurheartj.a061200. [DOI] [PubMed] [Google Scholar]
  29. Yanagisawa T., Satoh K., Taira N. Excitation of autonomic nerves by 4-aminopyridine in the isolated, blood-perfused sino-atrial node preparation of the dog. Eur J Pharmacol. 1978 May 15;49(2):189–192. doi: 10.1016/0014-2999(78)90077-8. [DOI] [PubMed] [Google Scholar]
  30. Yanagisawa T., Taira N. Positive inotropic effect of 4-aminopyridine on dog ventricular muscle. Naunyn Schmiedebergs Arch Pharmacol. 1979 Jul;307(3):207–212. doi: 10.1007/BF00505935. [DOI] [PubMed] [Google Scholar]
  31. Yeh J. Z., Oxford G. S., Wu C. H., Narahashi T. Interactions of aminopyridines with potassium channels of squid axon membranes. Biophys J. 1976 Jan;16(1):77–81. doi: 10.1016/S0006-3495(76)85663-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. de Faire U., Lundman T. Attempted suicide with verapamil. Eur J Cardiol. 1977 Oct-Nov;6(3):195–198. [PubMed] [Google Scholar]
  33. van der Meer J., van der Wall E. Fatal acute intoxication with verapamil. Neth J Med. 1983;26(5):130–132. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES