EVIDENCE THAT THE POSITIVE INOTROPIC EFFECTS OF THE ALKYLXANTHINES ARE NOT DUE TO ADENOSINE RECEPTOR BLOCKADE

The potency of 8-phenyltheophylline, theophylline and enprofylline as adenosine antagonists was assessed in vitro, using the guinea-pig isolated atrium, and in vivo, using the anesthetized dog. The order of potency of the alkylxantines as antagonists of the negative inotropic response to 2-chloroadenosine in vitro, and of the hypotensive response to adenosine in vivo was 8-phenyltheophylline > theophylline > enprofylline. The order of potency of the alkylxanthines as positive inotropic and chronotropic agents in the anesthetized dog was enprofylline > theophylline > 8-phenyltheophylline. Evidently, the inotropic effects of the alkylxanthines in the anesthetized dog are not due to adenosine receptor blockade.