Supplementary Observations on Matsubara Cancer Reaction (Fortification of the Action of Specific Intracutaneous Reaction for Cancer)

Matsubara, Masaka; Mori, T.

doi:10.2169/internalmedicine1962.9.215

Cited by 1 publication

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“…These results suggest that chronic administration of KRH-594, or of candesartan cilexetil, should produce a long-lasting and stable antihypertensive effect. Indeed, in clinical studies, candesartan cilexetil (4 and 8 mg once a day) has already been found to reduce blood pressure in essential hypertensive patients, the effect continuing for 24 h without any effects on the normal circadian variation [31,32]. This being so, it is possible that KRH-594 may have a similar long-lasting and stable antihypertensive effect in essential hypertensive patients.…”

Section: Discussionmentioning

confidence: 99%

Effects of the New Angiotensin II Type 1 Receptor Antagonist KRH-594 on Several Types of Experimental Hypertension

Inada

Murakami

Kaido

et al. 2011

Arzneimittelforschung

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The antihypertensive effect of dipotassium (Z)-2-[[5-ethyl-3-[2'-(1H- tetrazol-5-yl)biphenyl-4-yl]methyl-1,3,4-thiadiazoline-2- ylidene]aminocarbonyl]-1-cyclopentenecarboxylate (CAS 169328-25-0, KRH-594), a new angiotensin II type 1 (AT1) receptor antagonist, was studied in several experimental hypertensive models. The effects of KRH-594 on the circulating reninangiotensin system and on renal function were also investigated. Oral administration of KRH-594 (0.3 or 1 mg/kg) dose-dependently inhibited the angiotensin II-induced pressor response in common marmosets. KRH-594 (1, 3, or 10 mg/kg p.o.) dose-dependently exerted a long-lasting antihypertensive effect in spontaneously hypertensive rats (SHRs) and in 2-kidney 1-clip renal hypertensive rats (RHRs). Furthermore, repeated oral administration of KRH-594 (3 or 10 mg/kg/d) reduced blood pressure dose-dependently in SHRs, RHRs, and renal hypertensive dogs without tachycardia and with no evidence of a rebound phenomenon following drug withdrawal. On the other hand, in deoxycorticosterone acetate salt rats and normotensive rats, KRH-594 (10 or 30 mg/kg p.o.) did not have significant effects on systolic blood pressure. In SHRs, KRH-594 (3 or 10 mg/kg/d p.o. for 2 weeks) dose-dependently increased both plasma renin activity and the plasma angiotensin I concentration, but had no effect on the urinary excretion of sodium, potassium, and chloride or on creatinine clearance. These results suggest that KRH-594 should be effective in patients with essential or renal hypertension.

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Section: Discussionmentioning

confidence: 99%