title: In vivo characterisation of ZM 241385, a selective adenosine A2A receptor antagonist.
abstract: 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 A2A 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 A3/A1 receptor agonist N(6)-2-(4-amino-3-iodophenyl)ethyladenosine (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 A2A receptors in the action of adenosine in vivo.
authors.affiliation: Cardiovascular and Metabolism Department, Zeneca Pharmaceuticals, Mereside, Macclesfield, Cheshire, UK.
authors.forename: J R
authors.initials: JR
authors.lastname: Keddie
authors.forename: S M
authors.initials: SM
authors.lastname: Poucher
authors.forename: G R
authors.initials: GR
authors.lastname: Shaw
authors.forename: R
authors.initials: R
authors.lastname: Brooks
authors.forename: M G
authors.initials: MG
authors.lastname: Collis
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology; D003655:Decerebrate State / Q000503:physiopathology; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply / Q000187:drug effects; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D011918:Rats, Inbred SHR; D012039:Regional Blood Flow / Q000187:drug effects; D014227:Triazines / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D002317:Cardiovascular Agents; D058915:Purinergic P1 Receptor Antagonists; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; C046507:N(6)-2-(4-amino-3-iodophenyl)ethyladenosine; D000241:Adenosine