Kobinger W, Walland A, Kadatz R
Naunyn Schmiedebergs Arch Pharmacol. 1976;292(2):105-11. doi: 10.1007/BF00498579.
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.
RA 642，即2,2'-[14,8-双（二乙氨基）-嘧啶并[5,4-d]嘧啶-2,6-二基]二（2-甲氧基乙基）亚氨基]二乙醇，先前已报道其全身给药时会导致高血压。在本实验中，向猫的椎动脉内注射50微克/千克的RA 642（椎动脉内注射）会引起高血压，而静脉注射相同剂量则无作用。由于该药物在延髓前方脑已被切除的猫中仍有效，但在脊髓动物中无效，因此得出其作用部位在延髓的心血管中枢。椎动脉内注射会增加血管系统的总外周阻力。静脉注射1毫克/千克该物质后，颈前神经节交感神经纤维的放电率与动脉血压平行增加。静脉注射1毫克/千克RA 642可降低在用β-肾上腺素能受体阻断药物预处理以研究压力感受器反射的迷走效应反应，并用地昔帕明促进反射的犬中，静脉注射血管紧张素引起的反射性心动过缓。因此，RA 642增加交感神经活动，并且在用地昔帕明治疗后，降低迷走反射活动。RA 642通过中枢作用刺激呼吸。该药物没有惊厥作用。
