Medicine and Health Sciences Commons^™

What Evidence Is Available On Aldosterone Antagonists For Use In Heart Failure With Preserved Ejection Fraction?, Vivian Loo, Laura Tsu

Pharmacy Faculty Articles and Research

This drug information question and answer sheet discusses the use of aldosterone antagonists for use in heart failure with preserved ejection fraction.

Small Molecule Antagonists Of The Urokinase (Upa): Urokinase Receptor (Upar) Interaction With High Reported Potencies Show Only Weak Effects In Cell-Based Competition Assays Employing The Native Upar Ligand, Melissa De Souza, Hayden Matthews, Jodi A. Lee, Marie Ranson, Michael J. Kelso

Illawarra Health and Medical Research Institute

Binding of the urokinase-type plasminogen activator (uPA) to its cell-surface-bound receptor uPAR and upregulation of the plasminogen activation system (PAS) correlates with increased metastasis and poor prognosis in several tumour types. Disruptors of the uPA:uPAR interaction represent promising anti-tumour/metastasis agents and several approaches have been explored for this purpose, including the use of small molecule antagonists. Two highly potent non-peptidic antagonists 1 and 2 (IC50 1 = 0.8 nM, IC50 2 = 33 nM) from the patent literature were reportedly identified using competition assays employing radiolabelled uPAR-binding uPA fragments and appeared as useful pharmacological tools for studying the PAS. Before …

Muscarinic Receptor Antagonists, The Overactive Bladder And Efficacy Against Urinary Urgency, Kylie J. Mansfield

Graduate School of Medicine - Papers (Archive)

The overactive bladder (OAB) is a debilitating condition in which patients suffer from urinary urgency, frequency and nocturiawith or without urge urinary incontinence. The mainstay of pharmacotherapy for OAB is muscarinic receptor antagonists, which havebeen shown to be effective treatments for the symptoms of OAB. The mechanism underlying the efficacy of antimuscarinic agentsagainst the symptoms of OAB is not completely understood. This review explores the role of bladder mucosal muscarinic receptors in the signaling pathways that are activated in response to bladder filling. The cholinergic system is seen to be involved in bladder afferent signaling at many levels and as …

Phosphorylation-Induced Conformational Switching Of Cpi-17 Produces A Potent Myosin Phosphatase Inhibitor, Masumi Eto, Toshio Kitazawa, Fumiko Matsuzawa, Sei-Ichi Aikawa, Jason A. Kirkbride, Noriyoshi Isozumi, Yumi Nishimura, David L. Brautigan, Shin-Ya Ohki

Department of Molecular Physiology and Biophysics Faculty Papers

Phosphorylation of endogenous inhibitor proteins specific for type-1 Ser/Thr phosphatase (PP1) provides a mechanism for reciprocal coordination of kinase and phosphatase activities. Phosphorylation of Thr38 in the inhibitor protein CPI-17 transduces G-protein-mediated signaling into a > 1000-fold increase of inhibitory potency toward myosin phosphatase. We show here the solution NMR structure of phospho-T38-CPI-17 with r. m. s. d. of 0.36 ± 0.06 Å for the backbone secondary structure, which reveals how phosphorylation triggers a conformational change and exposes the PP1 inhibitory surface. This active conformation is stabilized by the formation of a hydrophobic core of intercalated side-chains, which is not formed …

Nicotinic Receptor Antagonists In The Treatment Of Neuropharmacological Disorders, Peter A. Crooks, Linda P. Dwoskin, Alain Ravard

Pharmaceutical Sciences Faculty Patents

Nicotine analogs that have nicotinic receptor antagonist properties. These compounds have been shown to competitively inhibit dopamine release induced by nicotine. The nicotine analog compounds are useful in the treatment of nicotine abuse, smoking cessation therapy, as an antidote for nicotine intoxication, treatment of cognitive disorders such as Alzheimer's disease and for the treatment of Parkinson's disease.

Aminoalkylpyridine Compounds Which Are Useful As Anticonvulsant Drugs, Excitatory Amino Acid Inhibitors And Nmda Sigma Receptor Antagonists, Pankaja K. Kadaba

Pharmaceutical Sciences Faculty Patents

Pharmaceutical compositions comprise as the active ingredient potent orally active, nonneurotoxic anticonvulsant compounds that are excitatory amino acid and NMDA/sigma receptor antagonists . . .

To read the remainder of this abstract, please download this patent.