RA 642, 2,2'-[14,8-bis(diethylamino)-pyrimido[5,4-d]
pyrimidine-2,6-diyl)di-(2-methoxyethyl)-imino]diethanol, has formerly been described to hypertensive when administered systemically. In the present experiments injection of 50 mug/kg
RA 642 into the vertebral artery (i.a. vert.) of the cat exerted
hypertension, while the same dose given intravenously (i.v.) elicited no effect. Since the
drug was still effective in cats of which the brain was removed rostrad of the myelencephalon but not in spinal animals, its site of action was concluded to be in cardiovascular centres of the medulla oblongata. An i.a. vert. injection increased total peripheral resistance of the vasculature. The electrical discharge rate in preganglionic cervical sympathetic nerve fibres increased in parallel to the arterial blood pressure following the i.v. injection of 1 mg/kg of the substance. 1 mg/kg
RA 642 i.v. decreased the reflex
bradycardia elicited by the i.v. injection of
angiotensin in dogs pretreated with a beta-
adrenoceptor blocking
drug to study the vagal effector reactions of the baroreceptor reflex, and treated with
clonidine to facilitate the reflex. Thus,
RA 642 increased sympathetic and, following
clonidine treatment, decreased vagal reflex activity.
RA 642 stimulated the respiration by a central action. The
drug had no
convulsant action.