cfm-2 and Disease-Models--Animal

cfm-2 has been researched along with Disease-Models--Animal* in 3 studies

Other Studies

3 other study(ies) available for cfm-2 and Disease-Models--Animal

ArticleYear
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
    Proceedings of the National Academy of Sciences of the United States of America, 2020, 12-08, Volume: 117, Issue:49

    When Zika virus emerged as a public health emergency there were no drugs or vaccines approved for its prevention or treatment. We used a high-throughput screen for Zika virus protease inhibitors to identify several inhibitors of Zika virus infection. We expressed the NS2B-NS3 Zika virus protease and conducted a biochemical screen for small-molecule inhibitors. A quantitative structure-activity relationship model was employed to virtually screen ∼138,000 compounds, which increased the identification of active compounds, while decreasing screening time and resources. Candidate inhibitors were validated in several viral infection assays. Small molecules with favorable clinical profiles, especially the five-lipoxygenase-activating protein inhibitor, MK-591, inhibited the Zika virus protease and infection in neural stem cells. Members of the tetracycline family of antibiotics were more potent inhibitors of Zika virus infection than the protease, suggesting they may have multiple mechanisms of action. The most potent tetracycline, methacycline, reduced the amount of Zika virus present in the brain and the severity of Zika virus-induced motor deficits in an immunocompetent mouse model. As Food and Drug Administration-approved drugs, the tetracyclines could be quickly translated to the clinic. The compounds identified through our screening paradigm have the potential to be used as prophylactics for patients traveling to endemic regions or for the treatment of the neurological complications of Zika virus infection.

    Topics: Animals; Antiviral Agents; Artificial Intelligence; Chlorocebus aethiops; Disease Models, Animal; Drug Evaluation, Preclinical; High-Throughput Screening Assays; Immunocompetence; Inhibitory Concentration 50; Methacycline; Mice, Inbred C57BL; Protease Inhibitors; Quantitative Structure-Activity Relationship; Small Molecule Libraries; Vero Cells; Zika Virus; Zika Virus Infection

2020
An alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate glutamate-receptor antagonist can inhibit premicturition contractions in rats with bladder outlet obstruction.
    BJU international, 2007, Volume: 100, Issue:1

    To explore the possible involvement of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) glutamate-receptors in bladder dysfunction associated with bladder outlet obstruction (BOO), as detrusor overactivity (DO) is common in men with benign prostatic hyperplasia.. Proposed mechanisms of DO include the myogenic or neurogenic theory, and the autonomous bladder hypothesis. In rats, BOO produces premicturition contractions (PMCs) that are assumed to be a consequence of inappropriate non-micturition activity during the filling phase. Using pharmacology, we explored the cause of PMCs to provide new insights into DO in humans. BOO was created in female Wistar rats; 6 weeks after obstruction we evaluated them using conscious-filling cystometry. A specific AMPA receptor antagonist, 1-(4'-aminophenyl)- 3,5-dihydro-7,8-dimethoxy-4H-2,3-benzodiazepin-4-one (CFM-2) was administered intravenously (i.v.) (0.003-3 mg/kg) or intrathecally (i.t.) (0.01-10 microg).. The i.v. administration of CFM-2 in rats with BOO significantly decreased the threshold pressure and micturition pressure. The most remarkable findings were that i.v. administration of CFM-2 in rats with BOO significantly and dose-dependently decreased the amplitude and number of PMCs. The highest dose of CFM-2 almost completely eliminated PMCs. The i.t. administration of CFM-2 had no significant effect on PMCs.. AMPA receptors have never been suggested as a neural mechanism of bladder dysfunction associated with BOO. Although PMCs in rats with BOO have been assumed to be mainly of myogenic origin, PMCs were suppressed by the i.v. administration of CFM-2. Thus, we think that PMCs have neurogenic components that are linked with AMPA receptors. In the present study, i.v. but not i.t. administration of CFM-2 suppressed PMCs, suggesting peripheral and/or supraspinal sites of inhibitory action of CFM-2 on PMCs.

    Topics: Animals; Benzodiazepinones; Disease Models, Animal; Female; Muscle Contraction; Rats; Rats, Wistar; Receptors, AMPA; Urinary Bladder Neck Obstruction; Urinary Bladder, Overactive; Urination; Urodynamics

2007
Synthesis and evaluation of pharmacological properties of novel annelated 2,3-benzodiazepine derivatives.
    Journal of medicinal chemistry, 2003, Aug-14, Volume: 46, Issue:17

    New cyclofunctionalized 2,3-benzodiazepines characterized by a triazolone or triazindione ring fused on the "c" edge of the heptatomic nucleus have been prepared. These compounds were evaluated as potential anticonvulsant agents, and some of them proved to be more potent noncompetitive 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionate (AMPA) receptor antagonists. In particular, 8,9-dimethoxy-6-(4-bromophenyl)-11H-[1,2,4]triazolo[4,5-c][2,3]benzodiazepin-3(2H)-one (5b) was almost 10-fold more active than GYKI-52466 and 3.5-fold more active than Talampanel. Furthermore, 5b potently reduced AMPA-evoked currents in electrophysiological experiments.

    Topics: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Animals; Anticonvulsants; Benzodiazepines; Disease Models, Animal; Epilepsy; Excitatory Amino Acid Agonists; In Vitro Techniques; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred DBA; Neurons; Olfactory Pathways; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Receptors, AMPA; Structure-Activity Relationship; Triazoles

2003
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