title: RA 642, a pyrimido-pyrimidine-derivative with vasodilating and hypertensive potency.
abstract: 2,2'-[(4,8-bis(diethylamino)-pyrimido[5,4-d]-pyrimidine-2,6-diyl)di-(2-methoxyethyl)imino]diethanol), RA 642, combines hypertensive and vasodilating effects. In anaesthetized animals arterial blood pressure was increased by i.v. doses of 0.25-4 mg/kg in cats and 0.025-0.25 mg/kg in dogs. In conscious dogs, 25 mm increase of mean blood pressure was achieved with 0.2 mg/kg i.v. and 18.8 mg/kg p.o. Cerebral blood flow was enhanced and calculated cerebral vascular resistance was reduced by RA 642. Total peripheral resistance was diminished by 0.25-1.0 mg/kg i.v. A vasodilatation of femoral and coronary vessels was shown after intraarterial injection. This effect as well as a BaCl2-antagonism in the isolation ileum is explained by a papaverine-like relaxant effect on smooth muscle. Activity on peripheral adrenergic receptors was excluded. Hypertension was abolished in spinalized cats, indicating a central mechanism of this effect.
mesh_terms: D000818:Animals; D001464:Barium / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003655:Decerebrate State; D004048:Diethylamines / Q000494:pharmacology; D004285:Dogs; D005260:Female; D005263:Femoral Artery / Q000502:physiology; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D013268:Stimulation, Chemical; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents
chemical_list: D004048:Diethylamines; D011743:Pyrimidines; D014665:Vasodilator Agents; D001464:Barium; C010650:RA 642