Assessment of affinities of propranolol and bopindolol to membranes from COS-7 cell transiently transfected with beta-1- and beta-2-adrenoceptors using a radioligand-binding assay method.
Activities of aqueous (AQU), methanolic (MET), methylene chloride (MC), and methylene chloride-methanol (MCM) extracts of TS were evaluated on isolated rat aortic rings precontracted with phenylephrine (PE) or high KCl.
The FDA approved HIV-1 protease inhibitors, ritonavir, saquinavir, and indinavir, are very effective in inhibiting HIV-1 replication, but their long-term efficacy is unknown. Since in vivo efficacy depends on access of these drugs to intracellular sites where HIV-1 replicates, we determined whether these protease inhibitors are recognized by the MDR1 multidrug transporter (P-glycoprotein, or P-gp), thereby reducing their intracellular accumulation. In vitro studies in isolated membrane preparations from insect cells infected with MDR1-expressing recombinant baculovirus showed that these inhibitors significantly stimulated P-gp-specific ATPase activity and that this stimulation was inhibited by SDZ PSC 833, a potent inhibitor of P-gp. Furthermore, photoaffinity labeling of P-gp with the substrate analogue [125I]iodoarylazidoprazosin (IAAP) was inhibited by all three inhibitors. Cell-based approaches to evaluate the ability of these protease inhibitors to compete for transport of known P-gp substrates showed that all three HIV-1 protease inhibitors were capable of inhibiting the transport of some of the known P-gp substrates but their effects were generally weaker than other documented P-gp modulators such as verapamil or cyclosporin A. Inhibition of HIV-1 replication by all three protease inhibitors was reduced but could be restored by MDR1 inhibitors in cells expressing MDR1. These results indicate that the HIV-1 protease inhibitors are substrates of the human multidrug transporter, suggesting that cells in patients that express the MDR1 transporter will be relatively resistant to the anti-viral effects of the HIV-1 protease inhibitors, and that absorption, excretion, and distribution of these inhibitors in the body may be affected by the multidrug transporter.
In pH 2.8~3.6 HCl-NaAc buffer solution, eosin Y (EY) can react with verapamil hydrochloride(VP) to form a 1:1 ion-association complex, which not only causes the change of absorption spectra and the quenching of fluorescence, but also results in the great enhancement of resonance Rayleigh scattering (RRS). Furthermore, a new RRS spectrum with the maximum wavelength at 324 nm will appear. In this work, the spectral characteristics of absorption, fluorescence and resonance Rayleigh scattering spectra, the optimum conditions for the reaction, the influencing factors and the analytical properties have been investigated. Thereby, a sensitive, simple, rapid and new method for the determination of VP by using eosin Y as a probe has been developed. The detection limit is 0.95 ng/mL for RRS method, 6.4 ng/mL for fluorophotometry and 0.18 μg/mL for spectrophotometric method. The absorbance, RRS and fluorescence intensity is proportional to the concentration of VP in the range of 0.6036~4.0 μg/mL, 0.0032~4.5 μg/mL and 0.0213~4.0 μg/mL, respectively. The effects of the reaction of verapamil hydrochloride and eosin Y on the absorption, fluorescence and resonance Rayleigh scattering spectra have been investigated. Meanwhile, the influences of coexisting substances are tested by RRS method and the results show that this method can be satisfactorily applied to the determination of VP in tablet and human serum samples. The composition and structure of the ion-association complex and the reaction mechanism are discussed. Moreover, the energy transfer among absorption, fluorescence and RRS was investigated briefly in this work.
Despite all medical therapies and splenectomy performed, severe life-threatening thrombocytopenia persists in many adult patients.
The effect of Myristica fragrans is similar to Verapamil and therefore it can be used effectively in the treatment of peptic ulcer and all other conditions that require calcium channel blockers for the treatment of these disorders.
Tilianin is the substrate of P-gp, BCRP and SGLT1. The effluent effect of P-gp and BCRP is the main mechanism of tilianin in intestinal absorption, indicating that tilianin can realize intestinal absorption and transport by relying on SGLT1. Tilianin is not the substrate of bile salt transporter protein.
The objectives of this analysis were to assess HR patterns in two populations (patients with chronic stable angina or stage I to III hypertension) and to compare the effects of various antianginal and antihypertensive treatments on HR.
The purpose of this study was to investigate the pathways involved in rhodamine 123 (R-123) accumulation enhancement in Caco-2 cells with a low molecular-weight methoxypolyethylene glycol-block-polycaprolactone (MePEG-b-PCL) diblock copolymer.
In brief, 11C-verapamil (approximately 0.2 mCi/kg) was administered to healthy volunteers (n = 12 [6 women and 6 men]) as an intravenous infusion over a period of approximately 1 minute before and after at least a 1-hour infusion of cyclosporine (2.5 mg x kg(-1) x h(-1)). Arterial blood samples and brain positron emission tomography images were obtained at frequent intervals for 45 minutes. Both blood and plasma radioactivity contents were determined in each verapamil sample. The content of verapamil and its metabolites in the 20- and 45-minute plasma samples was determined by a rapid solid-phase extraction method. The brain uptake of 11C-radioactivity (brain area under the curve [AUCbrain ]/blood area under the curve [AUCblood]) was determined in the presence and absence of cyclosporine.