Search results for "Potency"
showing 10 items of 122 documents
Relaxation by β3-adrenoceptor agonists of the isolated human internal anal sphincter
2009
In this study, responses of beta(3)-adrenoceptor agonists were examined on human isolated internal anal sphincter (IAS) in order to explore their relaxant effects on hypertonicity of IAS.The relaxant efficacy (E(max)) and potency (-logIC(50)) of BRL37344 and SR58611A, beta(3)-adrenoceptor agonists, were examined in contracted IAS muscle strips. The presence of beta(3)-adrenoceptors, and changes in intracellular calcium and cyclic nucleotide levels in IAS muscle were tested by Western blotting, epifluorescence microscopy and enzyme immunoassay, respectively.BRL37344 and SR58611A relaxed contracted IAS muscle (E(max)=27+/-3% and 35+/-3%; -logIC(50)=6.26+/-0.24 and 4.87+/-0.13; respectively). …
Risperidone in the Treatment of Disorders with a combined Psychotic and Depressive Syndrome - A Functional Approach
1992
In vitro receptor-binding profiles and in vivo pharmacological studies have shown risperidone to be a potent mixed serotonin-S2 dopamine-D2-like receptor antagonist. While anti-D2 activity may relate to the antipsychotic potency of neuroleptic drugs, an antidepressive efficacy of substances with anti-S2 activity has been suggested. In an open pilot-study, ten patients with schizodepressive disorders or a DSM-III-R diagnosis of psychotic major depressive episodes were treated with risperidone (2-10 mg/d) for six weeks. Weekly psychopathological evaluation was performed, including BPRS, SANS, SAPS, VAS scales, and AIMS and UKU for the assessment of side-effects. Generally, the psychotic syndr…
Pulsatile versus continuous oxytocin infusion for the oxytocin challenge test.
1994
In a prospective study, 140 patients had an oxytocin challenge test with either a continuous or a pulsed infusion (one minute of infusion in every five minutes). Both infusion regimens had similar success rates in terms of uterine contractions (97.1 vs 98.6%). The potency ratio (pulsed versus continuous infusion) was significant at 2.7 (1.27 to 5.2), which means that more uterine activity was induced with each mU of oxytocin with pulsatile than with continuous administration. The total amount of oxytocin required to obtain three good contractions in 10 minutes was about 40% less with pulsed administration than with continuous infusion, but the test took 40 minutes longer with the pulsed tha…
Endothelin receptors mediating contraction in goat cerebral arteries
1993
1. The aim of the present study was to identify the subtype of receptor mediating contraction to endothelin-1 and sarafotoxin S6b in goat isolated middle cerebral arteries. 2. Endothelin-1, endothelin-2 and endothelin-3 contracted cerebral arteries in a concentration-dependent manner. Although the three peptides were full agonists, the order of potency was endothelin-1 = endothelin-2 > endothelin-3, with a relative potency of endothelin-1 and endothelin-2 versus endothelin-3 of approximately 280. Sarafotoxin S6b induced concentration-dependent contractions with lower potency than endothelin-1/endothelin-2, higher potency than endothelin-3 and a higher maximum response than the three endothe…
Ability of the T cell-replacing polyanion dextran sulfate to trigger the alternate pathway of complement activation.
1973
Dextran sulfate (DS) consumed C3 in C4 deficient guinea pig serum. This temperature-dependent reaction required Mg++ ions and could therefore be blocked by EDTA. Isolated C3 was not influenced by DS, but serum factors were required for C3 consumption. The C3 proactivator as well as C3 were converted to their activated state by DS in guinea pig and human serum, as revealed by immunoelectrophoretical analysis. DS generated anaphylatoxin activity in serum. It is concluded that DS activates C3 via the alternate pathway of complement activation. This potency of the polyanion might serve as a tentative explanation for its T cell-replacing effect in an antibody-forming system, which was reported b…
Discovery of 5-benzyl-3-phenyl-4,5-dihydroisoxazoles and 5-benzyl-3-phenyl-1,4,2-dioxazoles as potent firefly luciferase inhibitors.
2013
Luciferase reporter assays are commonly used in high-throughput screening methods. Here, we report new firefly luciferase (FLuc) inhibitors based on 5-benzyl-3-phenyl-4,5-dihydroisoxazoles and 5-benzyl-3-phenyl-1,4,2-dioxazoles, which showed up as "false positives" in a luciferase reporter gene-based assay for nuclear receptor antagonists. The inhibition was shown to be noncompetitive for both natural enzyme substrates (d-luciferin and ATP) and selective to FLuc and proven to arise from a direct interaction between the enzyme and the inhibitor. Of the 63 evaluated compounds, 28 showed significantly better inhibition potency than the well-known inhibitor resveratrol (IC(50) = 59 nM), with fi…
Inhibition of inflammatory responses by epitaondiol and other marine natural products
1995
The marine metabolites pacifenol, stypotriol triacetate and epitaondiol were tested for their effects on a number of inflammatory responses. Epitaondiol exhibited a potent topical anti-inflammatory activity related to inhibition of leukocyte accumulation. The other compounds showed a lower potency, similar to that of indomethacin. None of the compounds affected superoxide generation by human neutrophils but pacifenol effectively inhibited the degranulation response. This compound and epitaondiol decreased the release of eicosanoids with a higher potency on the cyclo-oxygenase pathway. Only epitaondiol inhibited human recombinant synovial phospholipase A2 activity in a concentration-dependen…
COX-1/COX-2 inhibitors based on the methanone moiety
2002
This paper focuses on the synthesis and the in vitro testing of dual COX-1/COX-2 inhibitors. Starting from structures of non-steroidal anti-inflammatory drugs (NSAIDs) the diaryl methanone element was chosen as a lead. Modifications were carried out on this scaffold to obtain potent inhibitors of the COX enzymes. The N-(2-aroylphenyl)sulphonamides and -amides were studied in detail, and to consolidate the data evaluated the corresponding 3- and 4-regioisomers were also investigated. The potency and the enzyme selectivity were varied by structural modifications of the lead.
Tucupentol, a novel mono-tetrahydrofuranic acetogenin from Annona montana, as a potent inhibitor of mitochondrial complex I.
2009
Ten acetogenins, one of them new, were isolated from leaves and twigs of a Bolivian collection of Annona montana. The new compound that we named tucupentol (1) is a mono-tetrahydrofuranpentahydroxy-acetogenin. The inhibitory potency of tucupentol (1) on the mitochondrial complex I was evaluated, and this activity was compared with that of the known acetogenins, annonacin-A, cisannonacin-10-one, aromin, and gigantetronenin, also isolated from this plant material. The mentioned acetogenins acted as selective inhibitors of mitochondrial complex I in the 0.8-5.4-nM range. Fil: Álvarez Colom, Olga. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química …
Role of genetic factors on the effect of additional loading doses and two maintenance doses used to overcome clopidogrel hyporesponsiveness.
2014
Background and objective: Additional loading doses and higher maintenance doses (MDs) have been used to overcome hyporesponsiveness of clopidogrel. We aimed to investigate whether genetic polymorphisms of two cytochromes (CYP2C19 and CYP2C9) and ABCB1 modify effect of such dose-adjustment strategy.Materials and methods: We enrolled 118 patients undergoing elective or acute percutaneous coronary intervention (PCI) with drug eluting stent (DES). Platelet reactivity index (PRI) was measured using the vasodilator-stimulated phosphoprotein (VASP) index and a cut-off value of ≥60% was defined as hyporesponsiveness. Polymorphism of two cytochromes (CYP2C19, CYP2C9) and gene ABCB1 were determined. …