THE POTENTIATION OF CARDIAC RESPONSES TO ADENOSINE BY BENZODIAZEPINES

  • 1 January 1982
    • journal article
    • research article
    • Vol. 222  (3) , 752-758
Abstract
The concentration-related sensitization of guinea pig left atria to adenosine produced by 6 benzodiazepines and dipyridamole was analyzed with a quantitative procedure which theoretically yields the pKi (-log equilibrium dissociation constant) of an uptake inhibitor for the site of uptake. Four benzodiazepines produced sensitization of atria to adenosine and no alteration of responses to 2-chloroadenosine (a purine agonist which is not a substrate for adenosine uptake or degradation), the rank order of potency being diazepam (pKi = 5.6) .mchgt. oxazepam (4.6) > clonazepam (4.3) = lorazepam (4.2). Chlordiazepoxide and prazepam produced little sensitization to adenosine, but a concentration-related antagonism of responses to 2-chloroadenosine. Prior inhibition of adenosine uptake with dipyridamole unmasked antagonism of responses to adenosine by these 2 benzodiazepines as well, indicating a dual self-canceling effect (for inhibition of adenosine uptake; chlordiazepoxide, pKi = 5.0; prazepam, pKi = 4.8). Although benzodiazepines have been shown to inhibit uptake of adenosine in the CNS, the potency of these drugs and dipyridamole is more in accord with inhibition of a myocardial uptake process distinct from the synaptosomal transport of adenosine.