Therapeutic Potential of Monteplase in Acute Myocardial Infarction

Inoue, Teruo; Nishiki, Ryoichi; Kageyama, Manabu; Node, Koichi

doi:10.2165/00129784-200505040-00002

Cited by 3 publications

(2 citation statements)

References 28 publications

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“…Alternatively, the therapeutic efficacy of t-PA molecules is being enhanced by lowering its affinity for endogenous inhibitors via rational design as demonstrated in tenecteplase. Newer variants include duteplase [104] and monteplase [105]. Notwithstanding the success of t-PA therapeutics, it appears that alternative directions may be necessary for optimal thrombolytic therapy.…”

Section: Expanding the Protease Pharmacopeiamentioning

confidence: 99%

Proteases as therapeutics

Craik

Page

Madison

2011

Biochemical Journal

202

151

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Proteases are an expanding class of drugs that hold great promise. The U.S. FDA (Food and Drug Administration) has approved 12 protease therapies, and a number of next generation or completely new proteases are in clinical development. Although they are a well-recognized class of targets for inhibitors, proteases themselves have not typically been considered as a drug class despite their application in the clinic over the last several decades; initially as plasma fractions and later as purified products. Although the predominant use of proteases has been in treating cardiovascular disease, they are also emerging as useful agents in the treatment of sepsis, digestive disorders, inflammation, cystic fibrosis, retinal disorders, psoriasis and other diseases. In the present review, we outline the history of proteases as therapeutics, provide an overview of their current clinical application, and describe several approaches to improve and expand their clinical application. Undoubtedly, our ability to harness proteolysis for disease treatment will increase with our understanding of protease biology and the molecular mechanisms responsible. New technologies for rationally engineering proteases, as well as improved delivery options, will expand greatly the potential applications of these enzymes. The recognition that proteases are, in fact, an established class of safe and efficacious drugs will stimulate investigation of additional therapeutic applications for these enzymes. Proteases therefore have a bright future as a distinct therapeutic class with diverse clinical applications.

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Section: Expanding the Protease Pharmacopeiamentioning

confidence: 99%

Proteases as therapeutics

Craik

Page

Madison

2011

Biochemical Journal

202

151

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“…Treatment requires administration of PAs in doses several orders of magnitude above physiological levels to attain therapeutic efficacy, posing a considerable risk of hemorrhage (Ridker et al, 1994). To date, modifications in the design and delivery of plasminogen activators to attain greater affinity for fibrin, longer circulation time, and greater resistance to inhibitors have been of rather modest clinical benefit (Keyt et al, 1994;Benedict et al, 1995;Liberatore et al, 2003;Rijken et al, 2004;Inoue et al, 2005).…”

mentioning

confidence: 99%

The Glycocalyx Protects Erythrocyte-Bound Tissue-Type Plasminogen Activator from Enzymatic Inhibition

Ganguly¹,

Murciano²,

Westrick³

et al. 2007

J Pharmacol Exp Ther

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Coupling tissue-type plasminogen activator (tPA) to carrier red blood cells (RBC) prolongs its intravascular life span and permits its use for thromboprophylaxis. Here, we studied the susceptibility of RBC/tPA to PA inhibitors including plasminogen activator inhibitor-1 (PAI-1) that constrain its activity and may reduce the duration of its effect. Despite lesser spatial and diffusional limitations, soluble tPA was far less effective than RBC/tPA in dissolving clots formed in vitro from blood of wildtype (WT) mice (40 versus 80% lysis at equal doses of tPA). Furthermore, after i.v. injection, soluble tPA lost activity faster in transgenic mice expressing a high level of PAI-1 than in WT mice, whereas the activity of RBC/tPA was unaffected. PAI-1 inactivated soluble tPA at equimolar ratios in vitro, but it had no effect on the amidolytic or fibrinolytic activity of RBC/tPA. RBC/ tPA was also more resistant than soluble tPA to in vitro inhibition by other serpins (␣ 2 -macroglobulin and ␣ 1 -antitrypsin) and pathologically high levels of glucose. However, coupling to RBC did not protect a truncated tPA mutant, Retavase, from plasma inhibitors. Chemical removal of the RBC glycocalyx negated tPA protection from inhibitors: tPA coupled to glycocalyx-stripped RBC bound twice as much 125 I-PAI-1 as did tPA coupled to naive RBC, and susceptibility of the bound tPA to inhibition by PAI-1 was restored. Thus, the RBC glycocalyx protects RBC-coupled tPA against inhibition. Resistance to high levels of inhibitors in vivo contributes to the potential utility of RBC/tPA for thromboprophylaxis.

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Endovascular Thrombolysis Using Monteplase for Non-chronic Deep Venous Thrombosis

Yamagami

Yoshimatsu

Tanaka

et al. 2010

Cardiovasc Intervent Radiol

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This study was designed to evaluate the usefulness of endovascular thrombolysis using monteplase for deep venous thrombosis (DVT). Between December 2005 and October 2009, at our institution nine endovascular thrombolysis treatments with monteplase were performed for symptomatic DVT in eight patients (6 women, 2 men; mean age, 56 (range, 15-80) years). In all, systemic anticoagulation administered by the peripheral intravenous route with heparin and/or thrombolysis with urokinase followed by anticoagulation with orally administered warfarin had been performed, and subsequently six endovascular treatments without monteplase were administered. However, DVT persisted, and endovascular treatments with monteplase were tried. In six (67%) of the nine procedures, DVT completely or almost completely disappeared after endovascular thrombolysis with monteplase. Mean dose of monteplase used was 2,170,000 IU. There was only one procedure-related complication. In one patient, just after thrombolysis with monteplase, bleeding at the puncture site and gingival bleeding occurred. Bleeding was stopped by manual astriction only. Endovascular thrombolysis with monteplase may be an effective treatment for DVT, even in cases resistant to traditional systemic anticoagulation and thrombolysis and endovascular procedures without monteplase.

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Therapeutic Potential of Monteplase in Acute Myocardial Infarction

Cited by 3 publications

References 28 publications

Proteases as therapeutics

Proteases as therapeutics

The Glycocalyx Protects Erythrocyte-Bound Tissue-Type Plasminogen Activator from Enzymatic Inhibition

Endovascular Thrombolysis Using Monteplase for Non-chronic Deep Venous Thrombosis

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