The present experiment was designed to investigate the role of peripheral dopamine D1-like receptors and to evaluate the prophylactic effect of zelandopam, a dopamine D1-like receptor agonist, on puromycin aminonucleoside (PA)-induced nephrosis in rats. Rats were divided into six groups (n=10 per group): 0.9% saline-injected rats (control); PA-injected rats (PAN); PA-injected rats treated with the selective dopamine D1-like receptor agonist zelandopam (30, 100, 300 mg/kg p.o. twice a day); PA-injected rats treated with prednisolone (1 mg/kg p.o. once a day). Nephrosis was induced in rats with a single intravenous injection of PA at a dose of 50 mg/kg. The effects of zelandopam and prednisolone in PA nephrosis rats were evaluated before injection of PA and at 7 and 14 days after injection. PA-induced nephrosis was characterized by an increase in urinary protein excretion (proteinuria) and plasma total cholesterol. Zelandopam dose-dependently attenuated the increase in proteinuria and total cholesterol. Prednisolone significantly attenuated the increase in proteinuria and total cholesterol and resulted in a significant decrease in body weight. The present study demonstrates for the first time that zelandopam, a selective dopamine D1-like receptor agonist, is effective in blunting the development of PA-induced nephrosis, and that the effects of zelandopam are dose dependent.

01 Feb 2003·European Journal of PharmacologyQ3 · MEDICINE

Preventive effect of zelandopam, a dopamine D1 receptor agonist, on cisplatin-induced acute renal failure in rats

Q3 · MEDICINE

Article

Author: Osamu Inagaki ; Takeyuki Yatsu ; Motonori Aoki

To elucidate the role of peripheral dopamine D1 receptors in cisplatin-induced acute renal injury, effect of zelandopam (YM435, (-)-(S)-4-(3,4-dihydroxyphenyl)-7,8-dihydroxy-1,2,3,4-tetrahydroisoquinoline hydrochloride hydrate), a selective renal dopamine D1 receptor agonist, on cisplatin-induced acute renal failure in rats was studied. Rats were divided into six groups: control, cisplatin and cisplatin plus zelandopam (30, 100, 300 mg/kg p.o. twice, 75 and 15 min before cisplatin injection) or the free radical scavenger CV-3611 (2-O-octadecylascorbic acid, 10 mg/kg p.o., 75 min before cisplatin injection) treated groups. Rats received intraperitoneal injection of cisplatin at a dose of 5 mg/kg. Four days after cisplatin injection, plasma creatinine, blood urea nitrogen and body weight were measured and the kidneys were removed for histological examination. Cisplatin induced acute renal failure characterized by the increases in plasma creatinine and blood urea nitrogen with tubular damage, and decreased body weight. Zelandopam dose-dependently prevented all these changes. The free radical scavenger CV-3611 significantly attenuated a decrease in body weight and renal dysfunction without reducing tubular damage. The present study is the first demonstration for that a selective dopamine D1 receptor agonist is effective in preventing acute renal failure induced by cisplatin.

16 May 2000·CirculationQ1 · MEDICINE

Dopamine as a Novel Antioxidative Agent for Rat Vascular Smooth Muscle Cells Through Dopamine D ₁ -Like Receptors

Q1 · MEDICINE

Article

Author: Kano, Hiroaki ; Yoshikawa, Junichi ; Yasunari, Kenichi ; Kohno, Masakazu ; Minami, Mieko

Background —To elucidate the roles of vascular D 1 -like receptors in atherosclerosis, the effects of the specific D 1 -like agonists on platelet-derived growth factor (PDGF)-BB–mediated oxidative stress in vascular smooth muscle cells (VSMCs) were studied. Methods and Results —Immunohistochemical studies demonstrated the coexistence of D 1A and D 1B dopamine receptors in VSMCs. Western blotting revealed a band of ≈70 kDa for D 1A and D 1B dopamine receptors. VSMCs stimulated by PDGF-BB exhibited increased oxidative stress directly measured by flow cytometry. These effects were prevented by dopamine, SKF 38393, or YM 435, and this prevention was reversed by Sch 23390. These effects were blocked by a specific protein kinase A (PKA) inhibitor, N -(2-[ p -bromocinnamylamino]ethyl)-5-isoquinolinesulfonamide (H 89). The PDGF-BB–mediated increase in oxidative stress of VSMCs was significantly suppressed by the indirect phospholipase D (PLD) inhibitor suramin or the specific protein kinase C (PKC) inhibitor calphostin C. Both antisense but neither sense nor scrambled oligonucleotides to D 1A and D 1B receptors inhibited dopamine-induced suppression of increase in oxidative stress of VSMCs induced by PDGF-BB. Conclusions —These findings suggest that vascular D 1 -like receptors (D 1A and D 1B receptors) inhibit any increase in oxidative stress of VSMCs, possibly through activation of PKA and suppression of PLD and PKC.

100 Deals associated with Zelandopam hydrochloride

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Indication	Highest Phase	Country/Location	Organization	Date
Heart Failure	Phase 2	-	Mochida Pharmaceutical Co., Ltd.	-
Heart Failure	Phase 2	-	Astellas Pharma, Inc.	-
Hypertension	Phase 2	-	Astellas Pharma, Inc.	-
Hypertension	Phase 2	-	Mochida Pharmaceutical Co., Ltd.	-

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