Blocking Effects of OPC-21268 and OPC-31260 (Vasopressin V1- and V2-Receptor Antagonists) on Vasopressin-Induced Constrictions in Isolated, Perfused Dog Femoral Arteries

Chiba, Shigetoshi; Tsukada, Miyoko

doi:10.1254/jjp.59.133

Cited by 8 publications

(2 citation statements)

References 11 publications

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“…In isolated, perfused dog femoral arteries, OPC-2 1268 dose-dependently inhibited vasoconstriction induced by AVP but not by ANG 11 or NE ( Fig. 5) (2). With intravenous administration to pithed Sprague-Dawley rats, OPC-2 1268 inhibited pressor responses of AVP in a dose-dependent manner but did not inhibit the responses to ANG I1 or NE ( 6) (19).…”

Section: Effects On Pressor Responses To Avpmentioning

confidence: 87%

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OPC‐21268: An Orally Effective, Nonpeptide Vasopressin V₁ Antagonist

Kohmoto

Serizawa

1993

Cardiovascular Drug Reviews

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Arginine vasopressin (AVP) is among the strongest vasoconstrictors (mediated by V, receptors) and is also an osmotic and body fluid regulator through renal water reabsorption (mediated by V, receptors). The classification of AVP receptors was originally based on intracellular mechanisms: CAMP-independent (V,) and CAMP-dependent (V,) pathways. The intracellular mechanisms of action of V, receptor was explained by the activation of phospholipase C and the subsequent mobilization of intracellular Ca2+ and activation of protein kinase C (10). The angiotensin I1 (ANG 11) type 1 receptor (vascular type) has a common intracellular signal transduction pathway. In patients with congestive heart failure (CHF) (13) and essential hypertension (HT) (3), plasma concentrations of AVP and ANG II are elevated although vascular tone is usually inadequately high in these conditions. Inhibition of ANG I1 action by angiotensin converting enzyme (ACE) inhibitors in HT and CHF have been successful (15); ACE inhibitors improve the cardiac performance acutely via vasodilation and inhibition of water retention and also the long-term prognosis. Several studies suggest that direct cardiac effects of ANG I1 also play an important role in the long-term prognosis of CHF. An intravenous V, blocker decreases the blood pressure in patients with HT as do intravenous ANG I1 blockers. Cardiac muscle also has V, receptors (1).These reports suggest that a V, antagonist may have a similar beneficial effect in the treatment of HT and CHF as ACE inhibitors do. Many kinds of AVP antagonists have been developed for therapeutic use, but all were peptide analogues and do not have oral bioavailability (8). Recently, an orally active, nonpeptide form of V, antagonist, OPC-21268, has been selected from thousands of synthetic compounds (19). CHEMISTRYOPC-21268, i.e., 1-{ 1-[4-(3-acetylaminopropoxy)benzoyl]-4-pipe~dyl}-3,4-dihydro-2(1H)-quinolinone (Fig. l), was synthesized by Yamamura and colleagues of Otsuka

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Section: Effects On Pressor Responses To Avpmentioning

confidence: 87%

“…(2). With intravenous administration to pithed Sprague-Dawley rats, OPC-2 1268 inhibited pressor responses of AVP in a dose-dependent manner but did not inhibit the responses to ANG I1 or NE (Fig.…”

mentioning

confidence: 86%

OPC‐21268: An Orally Effective, Nonpeptide Vasopressin V₁ Antagonist

Kohmoto

Serizawa

1993

Cardiovascular Drug Reviews

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Diuretic Agents

Cervoni¹,

Chan²

2000

Kirk-Othmer Encyclopedia of Chemical Technology

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Diuretics are agents that increase urine output or flow. The effects of diuretic agents on electrolyte and water excretion in the kidney for the treatment of edema, congestive heart failure, ascites, and hypertension are reviewed. The structure and function of the kidney in the formation of urine are presented using the functional unit of the kidney, the nephron. The various sites where absorption, secretion, and the passive and active transport of water and electrolytes alter the composition of the glomerular filtrate from Bowman's capsule as it passes through the lumen of the nephron to the collecting ducts on its way to becoming urine are described. Diuretics are classified as low ceiling, high ceiling (loop), and potassium‐sparing diuretics, natriuretic peptides, atrial natriuretic peptides, atrial natriuretic peptide potentiators, osmotic diuretics, carbonic anhydrase inhibitors, methylxanthines, organomercurials, and aquaretics. The pharmacology, mechanisms or site of action in the nephron, and clinical effectiveness are discussed. Included is a discussion of the risk factors and side effects of diuretic agents.

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