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Results for “Drug Compounding”

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At least 307 records · Page 17Linked to original sources
PubMed2005

Mutational analysis of the yeast multidrug resistance ABC transporter Pdr5p with altered drug specificity.

Multidrug resistance ABC transporter Pdr5p of Saccharomyces cerevisiae is particularly important due to its ability to export a wide range of unrelated substrates. To clarify its function, we generated Pdr5p mutants by random mutagenesis and screened for mutants with altered drug specificity in vivo by using 5 drug compounds. Nine point mutations that caused significant changes in drug specificity distributed throughout the length of Pdr5p, namely, in the extracellular, transmembrane or cytoplasmic regions of the transporter. We then investigated their effects upon drug resistance, using 36 chemically related or distinct substrates. From this study, overall geometry of the Pdr5p was suggested to contribute in acquiring the enormous range of drug specificity. Based on their ability to inhibit the growth of the mutant strains, the 36 tested drugs were classified into: drugs to which the mutants responded differently (Group 1), drugs to which all the mutants showed sensitivity (Group 2), and drugs to which all the mutants exhibited resistance (Group 3). The ability of the compounds to be partitioned to the plasma membrane seemed an important factor for recognition by Pdr5p.

ATP-Binding Cassette Transporters↗
PubMed2006

Screening of an annotated compound library for drug activity in a resistant myeloma cell line.

PURPOSE: Resistance to anticancer drugs is a major problem in chemotherapy. In order to identify drugs with selective cytotoxic activity in drug-resistant cancer cells, the annotated compound library LOPAC1280, containing compounds from 56 pharmacological classes, was screened in the myeloma cell line RPMI 8226 and its doxorubicin-resistant subline 8226/Dox40. METHODS: Cell survival was measured by the Fluorometric Microculture Cytotoxicity Assay. RESULTS: Selective cytotoxic activity in 8226/Dox40 was obtained for 33 compounds, with the most pronounced difference observed for the glucocorticoids. A microarray analysis of the cells showed a difference in mRNA-expression for the glucocorticoid receptor suggesting potential mechanisms for the difference in glucocorticoid sensitivity. In the presence of the glucocorticoid-receptor antagonist RU486, the sensitivity to the glucocorticoids was reduced and a similar effect level in RPMI 8226 and 8226/Dox40 was achieved. CONCLUSION: In conclusion, screening of mechanistically annotated compounds on drug-resistant cancer cells can identify compounds with selective activity and provide a basis for the development of novel treatments of drug-resistant malignancies.

Antineoplastic Agents↗
PubMed2003

Spectroscopic approach for on-line monitoring of particle size during the processing of pharmaceutical nanoparticles.

A novel application of near-infrared (near-IR) spectroscopy for the on-line determination of nanoparticle size of a drug compound in a high solids dispersion is described. The on-line spectroscopic technique provides real-time data for process monitoring and control and overcomes the limitations that are encountered using laboratory-based instrumentation for nanoparticle size determination. Near-IR spectroscopy is capable of providing an accuracy of 2.4 nm near the endpoint of particle production, where the volume-weighted D90 particle size is determined to be 200-220 nm. The accuracy is adequate for endpoint control, which minimizes excess processing and provides control over the particle size throughout nanoparticle production.

Drug Compounding↗
PubMed1978

Genetic screening of compounds used in drug abuse treatment. I. Naltrexone hydrochloride.

Several compounds used clinically in drug abuse therapy were evaluated for genetic activity in a series of in vitro assays. This initial report describes the results for one of these compounds, Naltrexone. Nalrexone is a relatively nontoxic drug antagonist related to Naloxone which appears to be effective in diminishing the euphoria and dependence upon heroin in clinical studies. With the exception of weak nonspecific DNA damage observed in an E. coli DNA repair test and possibly with WI-38 cells as well, Naltrexone did not demonstrate significant potential for the induction of gene mutations or chromosomal aberrations under the conditions of this evaluation.

Animals↗
PubMed2000

The discovery of 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1 ,5-a]-pyrimidine: a corticotropin-releasing factor (hCRF1) antagonist.

Structure activity relationship studies led to the discovery of 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazo lo-[1,5-a]-pyrimidine 11-31 (DMP904), whose pharmacological profile strongly supports the hypothesis that hCRF1 antagonists may be potent anxiolytic drugs. Compound 11-31 (hCRF1 Ki = 1.0+/-0.2 nM (n = 8)) was a potent antagonist of hCRF1-coupled adenylate cyclase activity in HEK293 cells (IC50= 10.0+/-0.01 nM versus 10 nM r/hCRF, n = 8); alpha-helical CRF(9-41) had weaker potency (IC50 = 286+/-63 nM, n = 3). Analogue 11-31 had good oral activity in the rat situational anxiety test; the minimum effective dose for 11-31 was 0.3 mg/kg (po). Maximal efficacy (approximately 57% reduction in latency time in the dark compartment) was observed at this dose. Chlordiazepoxide caused a 72% reduction in latency at 20 mg/kg (po). The literature compound 1 (CP154526-1, 30 mg/kg (po)) was inactive in this test. Compound 11-31 did not inhibit open-field locomotor activity at 10, 30, and 100 mg/kg (po) in rats. In beagle dogs, this compound (5 mg/kg, iv, po) afforded good plasma levels. The key iv pharmacokinetic parameters were t1/2, CL and Vd,ss values equal to 46.4+/-7.6 h. 0.49+/-0.08 L/kg/h and 23.0+/-4.2 L/kg, respectively. After oral dosing, the mean Cmax, Tmax t1/2 and bioavailability values were equal to 1260+/-290 nM, 0.75+/-0.25 h. 45.1+/-10.2 h and 33.1%, respectively. The overall rat behavioral profile of this compound suggests that it may be an anxiolytic drug with a low motor side effect liability.

Animals↗