Disease relevance of R-29814

• It is concluded that neither alpha 1- and alpha 2- nor opiate-receptors are involved as the primary targets for R 28935 and its congeneric drugs to induce hypotension [1].
• In anaesthetized beagles with renal hypertension, the lowering of the blood pressure by R 28935, (0.02-0.64 mg/kg i.v.) is associated with a considerable decrease in the total peripheral vascular resistance, whereas the myocardial function is not affected [2].
• Significant postural hypotension during tilting, is induced by guanethidine and mecamylamine but not by R 28935 [2].

High impact information on R-29814

• Specific binding of threo 1-(1-[2-(1,4-benzodioxane-2-yl)-2-hydroxyethyl]4-piperidyl)-2-benzimidazolinone (R 29814), to rat brain membranes [3].
• Since the hypotensive activities of R 29814 and R 28935 greatly differ, it is concluded that the high affinity binding sites of 3[H]R 29814 as well as those of 3[H]R 28935 are not compatible with the sites responsible for the hypotensive effect [3].
• The influence of various alpha-adrenoceptor antagonists (phentolamine, yohimbine, R 28935, prazosine, terazosine) on clonidine's blood pressure effects at different steady state plasma concentrations was investigated in awake spontaneous hypertensive rats [4].
• R 28935 neither influenced resting heart rate nor the baroreceptor reflex response in beta-blocked dogs [5].
• The following surgical interventions did not diminish the central hypotensive action of R 28935: bilateral vagotomy, bilateral cervical sympathectomy, bilateral extirpation of the stellate ganglia [6].

Biological context of R-29814

• The decrease of the renal blood flow and the increase of the femoral blood flow, during hypothalamic stimulation were greatly reduced or reversed after R 28935 equals erythro-1-(1--e12-(1,4-benzodioxan-2-yl)-2-OH-Et]-4-piperidyl)-2-benzimidaxolinone, 80 mug/kg i.v., but not after clonidine, 5 mug/kg i.v [7].

Anatomical context of R-29814

• It is concluded that R 28935 is a potent blood pressure lowering drug, acting on the brain stem, presumably in the pontomedullary region--although the drug has no alpha-sympathomimetic activity [8].
• The carotid occlusion reflex is markedly reduced by low doses of R 28935 (40 to 80 mug/kg i.v.), whereas the pressor response elicited by electrical stimulation of the hypothalamus remains unimpaired [8].
• In the dog, erythro-1-[2-(1,4benzodioxan-2-yl)-2-OH-ET]-4-piperidyl)-2-benzimidazolinone (R 28935) lowers the blood pressure for several hours at dosages of 80 mug/kg when injected intravenously, of 10 mug/kg when injected into the vertebral artery and of 1.25 mug/kg when injected suboccipitally [8].

References