Merck + Co., Inc.

Robert J Gould

George D Hartman

Bohumil Bednar

Melissa S Egbertson

Steven A Nichtberger

Patricia A Rhymer

Lars Olofsson

Daniel F Veber

Ruth F Nutt

Dong-Mei Feng

Thomas M Connolly

Daniel M Bollag

Jules A Shafer

Michael F Sugrue

Jacquelynn J Cook

Frederic L Sax

Hybridomas and monoclonal antibodies for an anticoagulant test

The instant invention involves a combination therapy and pharmaceutical compositions comprised of a therapeutically effective amount of a cholesterol reducing agent such as an HMG-CoA reductase inhibitor in combination with a platelet aggregation inhibitor which is useful for inhibiting platelet aggregation, for inhibiting the formation of thrombotic occlusions, and for treating, preventing and reducing the risk of occurrence of cardiovascular and cerebrovascular events and related vaso-occlusive disorders.

Combination therapy for reducing the risks associated with cardiovascular disease

The present invention involves a combination therapy of administering a cholesterol reducing agent, such as a 3-hydroxy-3-methylglutaryl coenzyme a (HMG-CoA) reductase inhibitor and a platelet aggregation inhibitor for treating, preventing or reducing the risk of developing cardiovascular and cerebrovascular events and disorders in a mammal.

Anticoagulant test

A method for inhibiting platelet aggregation in a mammal comprising administering to the mammal a safe and therapeutically effective amount of a GPIIb/IIIa receptor antagonist or a pharmaceutically acceptable salt thereof and a safe and therapeutically effective amount of low molecular weight heparin. A method for inhibiting platelet aggregation in a mammal comprising administering to the mammal a safe and therapeutically effective amount of (2-S-(n-butylsulfonylamino)-3[4-(piperidin-4-yl)butyloxyphenyl]-propionic acid or a pharmaceutically acceptable salt thereof and a safe and therapeutically effective amount of low molecular weight heparin.

Platelet aggregation inhibition using low molecular weight heparin in

The present invention is a method for identifying a patient at risk to developing fibrinogen receptor antagonist-induced thrombocytopenia which comprises incubating patient plasma with a GPIIb/IIIa receptor:GPIIb/IIIa receptor antagonist complex to form a GPIIb/IIIa receptor:GPIIb/IIIa receptor antagonist:plasma antibody complex, incubating the GPIIb/IIIa receptor:GPIIb/IIIa receptor antagonist:plasma antibody complex with a secondary anti-human detectable antibody to form a GPIIb/IIIa receptor:GPIIb/IIIa receptor antagonist:plasma antibody:secondary anti-human detectable antibody complex, and detecting the presence of the secondary anti-human detectable antibody in the GPIIb/IIIa receptor:GPIIb/IIIa receptor antagonist:plasma antibody:secondary anti-human detectable antibody complex.

The compositions and methods of the invention provide a convenient means for systemically administering an integrin receptor antagonist or a pharmaceutically effective amount thereof to a patient by introducing the antagonist, in an ophthalmic formulation, to the patient's eye.

Methods for administering integrin receptor antagonists

Thrombin receptor binding peptides

The invention is directed to a series of novel compounds, and their pharmaceutically acceptable salts, of the formula ##STR1## wherein R is C.sub.0-6 alkyl substituted with R.sup.5 or a mono or polycyclic aromatic or heteroaromatic system comprised of 5 or 6-membered aromatic or heteroaromatic rings that are either unsubstituted or substituted with one or more of R.sup.1 and R.sup.2 ; R.sup.1 and R.sup.2 are independently C.sub.1-6 alkyl, carboxyl, hydroxyl, azido, nitro, amino, C.sub.1-6 alkylamino, C.sub.1-6 dialkylamino, arylamino, aryl C.sub.1-6 alkylamino, hydroxysulfonyl or arylazo; aryl is a phenyl or naphthyl ring which is unsubstituted or substituted with one or more of R.sup.3 and R.sup.4 ; R.sup.3 and R.sup.4 are independently C.sub.1-6 alkyl, azido, nitro, amino, C.sub.1-6 dialkylamino or hydroxysulfonyl; R.sup.5 is ##STR2## provided that when R is an unsubstituted monocyclic ring, the monocyclic ring is not phenyl or pyridyl. Such compounds are useful as fluorescent probes for identifying antiplatelet agents which selectively bind to activated platelets.

Compounds and methods for identifying activated platelets

The radioligands are six amino acid peptides having iodinated tyrosine at amino acid position six, including Ala-pFPhe-hArg-Cha-hArg-Tyr(I)-NH.sub.2, which mimic the activated form of the thrombin receptor protein. Thrombin receptor radioligands of the present invention are useful for screening for thrombin receptor antagonists.

Thrombin receptor radioligands

Compounds of the general formula ##STR1## and the pharmaceutically acceptable salts thereof wherein

Method of inhibiting osteoclast-mediated bone resorption by

Compounds of the general formula ##STR1## Y is an integer of from 0 to 6 is chosen from: O,

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Green Lane, PA, United States of America

Robert J Gould