Olprinone: A Phosphodiesterase III Inhibitor with Positive Inotropic and Vasodilator Effects

Mizushige, Katsufumi; Ueda, Takashi; Yukiiri, Kazushi; Suzuki, Hitoshi

doi:10.1111/j.1527-3466.2002.tb00085.x

Cited by 256 publications

(105 citation statements)

References 47 publications

(65 reference statements)

Supporting

Mentioning

104

Contrasting

Unclassified

Order By: Relevance

“…Various types of arteries in human [8] and animal [1,6] experiments have differential pharmacological sensitivities to PDE3 inhibitors, although the mechanism remains unknown. It has been shown that olprinone increases cerebral blood flow and that there is no direct correlation between changes in cerebral blood flow and cardiac output [3]. Although this finding suggests that the direct vasodilation may play an important role in the olprinone-induced change in cerebral blood flow, the direct effect of olprinone on the cerebral artery is poorly understood.…”

Section: Discussionmentioning

confidence: 98%

“…Although this finding suggests that the direct vasodilation may play an important role in the olprinone-induced change in cerebral blood flow, the direct effect of olprinone on the cerebral artery is poorly understood. The carotid artery plays a role in the regulation of cerebral blood flow, and recent studies have also revealed that the distensibility of the wall of the common carotid artery is improved by olprinone [3,14]. PDE3 inhibitors are known to have a potent vasodilation effect on renal and splanchnic arteries [4][5][6]15].…”

Section: Discussionmentioning

confidence: 99%

“…Olprinone, a relatively newly commercially available PDE3 inhibitor, is known to increase both cerebral [3] and visceral organ blood flow [4,5]. The vasodilation response to PDE3 inhibitors including amrinone and milrinone is not uniform among the different vascular beds including the renal and cerebral arteries [6,7].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Differential vasodilation response to olprinone in rabbit renal and common carotid arteries

et al. 2010

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Differential vasodilation response to olprinone in rabbit renal and common carotid arteries

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Imidazo[1,2-a]pyridines are important structural motifs in medicinal chemistry, such as zolpidem 63 63,64 , alpidem 64 65 , minodronic acid 65 66 , olprinone 66 67 , and zolimidine 67 68 ( Figure 11). The fluorination of imidazo[1,2-a]pyridines has recently been accomplished by Sun and coworkers.…”

Section: A3-imidazoheterocyclic Derivativesmentioning

confidence: 99%

Fluorination methods in drug discovery

2016

View full text Add to dashboard Cite

Fluorination reactions of medicinal and biologically-active compounds will be discussed. Late stage fluorination strategies of medicinal targets have recently attracted considerable attention on account of the influence that the fluorine atom can impart to targets of medicinal importance, such as a modulation of lipophilicity, electronegativity, basicity and bioavailability, this latter as a consequence of membrane permeability. Therefore, the recourse to late-stage fluorine substitution on compounds with already known and relevant biological activity can provide the pharmaceutical industry with new leads with improved medicinal properties. The fluorination strategies will take into account different fluorinating reagents, nucleophilic, electrophilic and of radical nature. Diverse families of organic compounds such as (hetero)aromatic rings, and aliphatic substrates (sp 3 , sp 2 , and sp carbon atoms) will be studied in late-stage fluorination reaction strategies. The omniphobicity/lipophilicity and electrostatic interactions can be considered among the most prominent effects. Thus, introducing fluorine into an organic compound can significantly alter its biological properties.One other subtle but important effect of introducing fluorine into the backbone of a medicinal target is the inflection of acidity and basicity of the parent compound 4 , which can change, inter alia, the binding affinity, and bioavailability. Highly basic groups can have a detrimental effect on the bioavailability of a drug. Thus introducing a fluorine atom next to a basic group can reduce its basicity, enhancing its membrane permeability, and increasing bioavailability. Although the replacement of hydrogen for fluorine does not have a profound steric influence, electrostatic interactions with other groups can change conformations significantly. The replacement of hydrogen for fluorine on aromatic rings is a well-known strategy to decelerate oxidative metabolic processes by Cytochrome P450 monooxygenases. In this respect, the electron-withdrawing properties of fluorine on aromatic rings, which can slow down hydrolytic metabolism, alter reaction rates and stability of intermediates. Fluorine substitution on aromatic rings is also known to increase binding affinity, as a result of enhancing electrostatic interactions.However, it is difficult to predict the influence of fluorine substitution on the overall profile in a given situation.As numerous reports attest 1 , the number of marketed drugs that contain a fluorine atom has increased rapidly. As of 2009, the FDA-had approved >140 fluorine-containing drugs. This review article is intended to present new synthetic methodologies 9 for accomplishing fluorination reactions on molecules (drugs/prodrugs) with pharmacological activity. It is not our aim (Figure 3). would be beneficial to the syntheses. 3a.-Conversion of C Ar -H into C Ar -F BondsXu and co-workers 38 have developed an ortho C-H bond fluorination of 2-phenoxyl pyridine derivatives through a palladium-catalyzed reaction v...

show abstract

“…Olprinone is a newly developed selective phosphodiesterase (PDE) type III inhibitor with combined positive inotropic and vasodilating properties through the elevation of intracellular cyclic adenosine monophosphate (cAMP) levels in vascular smooth muscle cells and cardiomyocytes by preventing the degradation of cAMP (1). In Japan, this agent is extensively used in the treatment of acute heart failure and myocardial depression after cardiac surgery.…”

Section: Introductionmentioning

confidence: 99%

Effect of Olprinone, a Phosphodiesterase Iii Inhibitor, on Hepatic Ischemia-Reperfusion Injury in Rats

Yamaguchi

Kawahara²,

Kumakura³

et al. 2010

Shock

View full text Add to dashboard Cite

I/R injury is the main cause for hepatic dysfunction and failure after liver transplantation and liver resection. Therefore, reduction of I/R injury is the most important goal to improve the outcome of these procedures. Olprinone is a newly developed selective phosphodiesterase III inhibitor, which has been reported to ameliorate renal I/R injury in rats. However, no clear evidence for the actions of olprinone on inflammatory response after hepatic I/R injury has been disclosed thus far. Our study was designed to evaluate the action of olprinone on the hepatic I/R injury in rats. Olprinone increased the cyclic adenosine monophosphate level in injured liver tissue and ameliorated the liver injury after hepatic I/R. Moreover, olprinone suppressed the activation of p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and nuclear factor-kappaB, cytokine production (TNF-alpha, IL-6, and cytokine-induced neutrophil chemoattractant factor 1), and intercellular adhesion molecule 1 expression in liver after hepatic I/R. These observations suggest that olprinone protects liver against I/R injury via the elevation of cyclic adenosine monophosphate level and suppression of intercellular adhesion molecule 1 expression and cytokine production (TNF-alpha, IL-6, and cytokine-induced neutrophil chemoattractant factor 1), possibly by interfering with the signaling pathways of p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and nuclear factor-kappaB in rats.

show abstract

Olprinone: A Phosphodiesterase III Inhibitor with Positive Inotropic and Vasodilator Effects

Cited by 256 publications

References 47 publications

Differential vasodilation response to olprinone in rabbit renal and common carotid arteries

Differential vasodilation response to olprinone in rabbit renal and common carotid arteries

Fluorination methods in drug discovery

Effect of Olprinone, a Phosphodiesterase Iii Inhibitor, on Hepatic Ischemia-Reperfusion Injury in Rats

Contact Info

Product

Resources

About