Additive competitive interaction of verapamil and quinidine at alpha-adrenergic receptors of isolated cardiac guinea pig myocytes and human platelets

Life Sci. 1988;42(6):667-77. doi: 10.1016/0024-3205(88)90458-4.


Recent clinical work has questioned the safety of a combined therapy of oral quinidine and intravenous verapamil, because some patients were reported to react with severe hypotension probably due to drug interactions with vascular alpha-adrenergic receptors. In order to obtain further quantitative information on the underlying mechanism, we used the radioligands (3H)-prazosin and (3H)-yohimbine to perform binding studies on intact cells, with predominantly alpha-1 (isolated myocytes) or alpha-2 subtypes (human platelets) of adrenergic receptors. Our studies confirm that both verapamil and quinidine possess a distinct alpha-adrenergic receptor blocking activity and do not discriminate between the alpha-1 and alpha-2 subtype (Ki-values were between 0.24-0.28 mumol/l for alpha-1 receptors and 0.49-0.50 mumol/l for alpha-2 receptors). Their interaction was competitive and in the presence of both drugs inhibition of radioligand binding was additive. The alpha-adrenergic blockade by verapamil was stereospecific as D-verapamil increased the dissociation constant of the radioligand to a much lesser degree than L-verapamil (Ki = 1.67 +/- 0.29 mumol/l for D-verapamil). The calcium channel blocker nitrendipine, a 1,4-dihydropyridine derivative, did not show any competition up to concentrations of 10 mumol/l. Our results thus give evidence that verapamil and quinidine have already at therapeutic blood levels significant alpha-adrenergic blocking activities which may be of clinical interest. In addition our results show that adult cardiac myocytes are very well suited for pharmacological adrenergic interaction studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive
  • Blood Platelets / metabolism*
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Drug Interactions
  • Guinea Pigs
  • Humans
  • Isomerism
  • Kinetics
  • Myocardium / metabolism*
  • Nitrendipine / pharmacology
  • Quinidine / pharmacology*
  • Receptors, Adrenergic, alpha / drug effects
  • Receptors, Adrenergic, alpha / metabolism*
  • Verapamil / pharmacology*


  • Receptors, Adrenergic, alpha
  • Nitrendipine
  • Verapamil
  • Quinidine