Preferential vasoconstrictor properties of acetazolamide on the arteries of the choroid plexus.
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Acetazolamide↗
Biomedical subjects
R Dixon
Publications and source records attributed to R Dixon.
Aqueous humor turnover rates in the cat. II. Effect of ouabain and chlorothiazide.
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Animals↗
The isolation and biosynthesis of highly polar steroids found in placental tissue.
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Adrenal Cortex Hormones↗
Biosynthesis of steroid sulfates by normal human testis.
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Androgens↗
Assessment of the involvement of CYP3A in the vitro metabolism of a new modulator of MDR in cancer chemotherapy, OC144-193, by human liver microsomes.
The novel substituted imidazole compound, OC144-093 exhibits potent biological activity in vitro and in vivo for reversal of P-glycoprotein (PgP) based resistance to cancer chemotherapy. Its mechanism of action relies upon its inhibitory interaction with the mdr1 gene product, a known mediator of multidrug resistance (MDR). Overlapping substrate specificities and tissue distribution of cytochrome P450 3A (CYP3A) and PgP indicate the potential for drug-drug interactions when modulator and anticancer agent are co-administered. We have examined the metabolism of OC144-093 in vitro using human liver microsomes to determine if CYP3A is involved. Our results show that OC144-093 is converted to one major metabolite (M1) in human liver microsomes which was identified by LCMS to be the O-deethylated derivative. Km and Vmax for O-deethylation were determined as 3.96+/-0.67 microM and 32.08+/-9.73 pmol/mg protein/min, respectively (n=3). Correlation studies conducted in a panel of human livers phenotyped for specific P450 enzyme activity showed a significant relationship between M1 formation and the activity of CYP2C9, CYP2B6, CYP2E1 and CYP3A4. Treatment of microsomes with carbon monoxide gas inhibited M1 formation and diethyldithiocarbamate and ketoconazole (>3 microM), non-specific CYP inhibitors, gave IC50 values of 124.4+/-21.6 microM and 25.3+/-3.2 microM respectively for the inhibition of O-deethylation, also implicating the involvement of CYP enzymes. Specific CYP inhibitors of CYP3A4 were essentially non-inhibitory to M1 formation. We can conclude therefore that OC144-093 is not extensively metabolised in human liver microsomes although conversion to its O-deethylated derivative does occur. Our data indicates that this conversion is not mediated by CYP3A4.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Development of radioimmunoassay for chlorpromazine.
Antiserum against chlorpromazine (CPZ) was produced in rabbits immunized with CPZ hapten conjugated to bovine serum albumin. The antiserum was used to develop a radioimmunoassay for CPZ. As little as 10 pg of CPZ can be detected with this radioimmunoassay. Major metabolites, CPZ sulfoxide, Nor1 -CPZ and Nor2 -CPZ are not bound significantly by the antibody unless the concentrations are very high. Although the antibody can bind 7-HO-CPZ, 8-HO-CPZ and promazine, the concentrations required to produce a 50% inhibition of 3H-CPZ-antibody binding are 5-10 times greater than CPZ. The plasma levels of CPZ and some minor metabolites in rats following administration of 10 mg/kg i.v. were determined by radioimmunoassay and showed a biphasic decay curve. Brain levels revealed that following i.v. administration CPZ traverses the blood-brain barrier rapidly and achieves peak concentration within 5 min. Plasma and brain levels can be detected for at least 24 hr.
Animals↗
Recommendations for the control of rubella within hospitals.
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Cross Infection↗
Biomedical ethics: seeking the best alternative.
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Canada↗