in this study, we investigated the interactive effects of intraperitoneal (i.p.) injections of three different phosphodiesterase inhibitors (pdeis) on morphine-induced analgesia in mice using tail-flick method. subcutaneous administration of morphine (1, 3 and 6 mg/kg) caused significant antinociceptive effects in a dose dependent manner. administration of pentoxifylline (12.5, 25, 50 and 100 m...

       In this study, we investigated the interactive effects of intraperitoneal (i.p.) injections of three different phosphodiesterase inhibitors (PDEIs) on morphine-induced analgesia in mice using tail-flick method. Subcutaneous administration of morphine (1, 3 and 6 mg/kg) caused significant antinociceptive effects in a dose dependent manner. Administration of pentoxifylline (12.5, 25, 50 an...

The subcellular distribution of plasminogen activator (PA) was studied in the human fibrosarcoma cell line HT 1080. The cells were homogenized and the cytoplasmic extract (postnuclear supernatant) was fractionated by rate sedimentation and isopyknic equilibration in continuous sucrose density gra dients. The distribution of PA was compared with that of a number of subcellular marker enzymes. PA...

Selective and nonselective cytochromes P450 (P450) chemical inhibitors and monoclonal antibodies (mAbs) are routinely used to determine the contribution of P450 enzymes involved in the biotransformation of a drug. A fluorometric assay has been established using fluorescein diacetate as a model substrate to determine the effect of some commonly used P450 inhibitors and mAbs on human liver micros...

cells possess the ability to suppress the growth of cocultivated malignant cells and that this inhibition can be modulated by the concentration of serum (2) or by the presence of phosphodi esterase inhibitors such as IBX (3). In neither case could the phenomenon be attributed to the presence of diffusible growth inhibitory factors in the culture medium, but, in the case of IBX, this inhibition ...

Carboxylesterases are essential enzymes in the hydrolysis and detoxification of numerous pharmaceuticals and pesticides. They are vital in mediating organophosphate toxicity and in activating many prodrugs such as the chemotherapeutic agent CPT-11. It is therefore important to study the catalytic mechanism responsible for carboxylesterase-induced hydrolysis, which can be accomplished through th...

Carboxylesterases are important enzymes responsible for the hydrolysis and metabolism of numerous pharmaceuticals and xenobiotics. These enzymes are potently inhibited by trifluoromethyl ketone containing (TFK) inhibitors. We demonstrated that the ketone hydration state was affected by the surrounding chemical moieties and was related to inhibitor potency, with inhibitors that favored the gem-d...

p-Nitrophenyl and cholesteryl-N-alkyl carbamates are good inhibitors of porcine pancreatic cholesterol esterase-catalyzed hydrolysis of p-nitrophenyl butyrate. p-Nitrophenyl-N-butyl and N-octyl carbamates (compounds 1 and 2, respectively) are potent active site-directed irreversible inhibitors of this enzyme. The inhibition of cholesterol esterase by compound 1 or 2 shows saturation kinetics wi...

Tenofovir disoproxil fumarate (TDF), the bisphosphonate ester prodrug of tenofovir (TFV), has poor bioavailability due to intestinal degradation and efflux transport. Reformulation using U.S. Food and Drug Administration-approved esterase and efflux inhibitors to increase oral bioavailability could provide lower dose alternatives and reduce costs for patients with HIV in resource-limited settin...