In vivo characterisation of ZM 241385, a selective adenosine A(2A) receptor antagonist

The in vivo characterisation of ZM 241385 (4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol), a novel, non-xanthine, selective adenosine A(2A) antagonist is described. In anaesthetised dogs ZM 241385 (i.v.) was 140-fold more potent in attenuating vasodilator responses to exogenous adenosine in the constant flow perfused hind limb than the bradycardic effects. In pithed rats in which blood pressure was supported by angiotensin II infusion, ZM 241385 (10 mg kg(-1), i.v.) did not inhibit the hypotensive or bradycardic effects of the A(3)/A(1) receptor agonist N-6-2-(4-amino-3-iodophenyl)ethyladenosin (APNEA). In conscious spontaneously hypertensive rats, ZM 241385 (3-10 mg kg(-1), p.o.) selectively attenuated the mean arterial blood pressure response produced by exogenous adenosine. No inhibition of the bradycardic effects of adenosine was observed following these doses of ZM 241385. The results indicate that ZM 241385 can be used to evaluate the role of adenosine A(2A) receptors in the action of adenosine in vivo.