RA 642, a pyrimido-pyrimidine-derivative with vasodilating and hypertensive potency.

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.