Skip to main content
Log in

Pharmacodynamic interaction between mibefradil and other calcium channel blockers

  • Original Article
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract.

Briefly after withdrawal of the (T-type) calcium channel blocker mibefradil from the market, four cases of life-threatening interaction of mibefradil with dihydropyridines were reported. We investigated in vitro whether mibefradil interacts with a dihydropyridine, as described for other non-dihydropyridine compounds. Rat working hearts were used to examine functional interactions between amlodipine and mibefradil. Gallopamil and another T-type-channel blocker, ethosuximide, were included for comparison. Effects of mibefradil, (+)- and (–)-gallopamil on [3H](+)-isradipine binding were studied in membranes from tsA201-cells transfected with α1C-, α2δ-, and β1a- or β2a-calcium channel subunits.

Mibefradil increased negative inotropic effect of amlodipine, but not of gallopamil. Gallopamil and ethosuximide showed no influence on contractile effects of amlodipine. Furthermore, mibefradil concentration-dependently caused bradycardic rhythm disturbance. The same type of arrhythmia was observed combining low concentrations of mibefradil with amlodipine, or with gallopamil, respectively. Amlodipine alone, or the combination of gallopamil or ethosuximide with amlodipine did not cause any arrhythmia. Binding studies showed a concentration-dependent positive allosteric interaction between [3H](+)-isradipine and mibefradil, but not with [3H](+)-isradipine and gallopamil enantiomers.

Molecular and functional evidence points to an interaction between a dihydropyridine and mibefradil. Mibefradil caused rhythm disturbances and potentiation of negative inotropy when combined with amlodipine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Author information

Authors and Affiliations

Authors

Additional information

Electronic Publication

Rights and permissions

Reprints and permissions

About this article

Cite this article

Matthes, J., Huber, I., Haaf, O. et al. Pharmacodynamic interaction between mibefradil and other calcium channel blockers. Naunyn-Schmied Arch Pharmacol 361, 578–583 (2000). https://doi.org/10.1007/s002100000239

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s002100000239

Navigation