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At least 19 recordsLinked to original sources

Stabilization by ethylenediaminetetraacetic acid of amide and other groups in drug compounds.

Ethylenediaminetetraacetic acid (EDTA) was shown to be effective in stabilizing pharmaceutical compounds, which contain acetamido groups, from degradation by light, e.g. paracetamol. Its addition is particularly effective in stabilizing such compounds from the action of ascorbic acid in the light or dark. EDTA was also shown to stabilize lignocaine, sulphadiazine and succinylsulphathiazole. Previous studies had shown that EDTA stabilizes the acetamido group present in two synthetic food colouring compounds.

Acetaminophen

Polymethylmethacrylate-antiblastic drug compounds: an in vitro study assessing the cytotoxic effect in cancer cell lines--a new method for local chemotherapy of bone metastasis.

An in vitro study was performed assessing the pharmacologic properties of polymethylmethacrylate (PMMA)-antiblastic agent (doxorubicin and cisplatinum) mixtures in normal and neoplastic cell lines cultures. The study's aim was to analyze the polymerization capacity of PMMA in the presence of doxorubicin and cisplatinum, the release of drug from the mixture, the kinetics of release, and the effect of the released drugs in normal and neoplastic cell cultures. Our data show that even at high concentrations neither doxorubicin nor cisplatinum inhibit the polymerization of PMMA. Moreover, mixtures in vitro can release the antiblastic drug which maintains its pharmacologic activity on sensitive neoplastic cells. Therefore, the PMMA-antiblastic drug mixtures, along with current anti-cancer therapy (systemic chemotherapy and radiation therapy), may provide better local control of the metastatic lesion and of some bone tumors.

Bone Neoplasms

A "carrier effect" observed in assay of antidiarrhoeal drug compounds.

A carrier effect has been shown to exist in a stable isotope dilution assay for diphenoxylate. When a tetradeuterated analogue is used as a carrier and internal standard a sevenfold increase in sensitivity is observed for the unlabelled compound. Examination of a related pharmacologically active compound (SC-27166) showed a much smaller effect.

Antidiarrheals

Alteration of enzyme specificity and catalysis by protein engineering.

New substrate specificities can be introduced into existing enzymes for the purpose of making them more suitable for the chemoenzymic synthesis of single compound drugs and other chiral compounds. The most productive route used in the past year has involved the utilization of the catalytic and substrate-binding properties from homologous enzymes found in nature, one example being the broadening of the substrate specificity of yeast alcohol dehydrogenase. Other highlights include the creation of thermostable dehydrogenases that will interconvert NADPH and NADH, and the design of mutant enzymes with improved catalytic rates compared with their wild-type counterparts.

Amino Acid Sequence

Inhibition of collagen peptidase in HeLa cells and human tumours by compounds including drugs used in cancer therapy.

Collagen-peptidase activity in extracts of HeLa cells and human tumours is inactivated by Razoxane (ICRF-159), cyclophosphamide, 5-fluorouracil, thiotepa, aprotinin, EDTA and phenanthroline. As this activity, in association with other enzymes, may contribute to tissue lysis in cancers, chemical intervention may reduce invasiveness and modify the processes of infiltration and metastasis. Accordingly, some drugs used in therapy or for the prevention of metastasis may produce their observed effects by a combination of factors including enzyme inhibition.

Antineoplastic Agents

Leveraging the genetics of psychiatric disorders to prioritize potential drug targets and compounds.

Genetics can inform biologically relevant drug development and repurposing, which may improve patient care. Here, we leverage the genetics of psychiatric disorders to prioritize potential drug targets and compounds. We used the genome-wide association studies of four psychiatric disorders [attention deficit hyperactivity disorder (ADHD), bipolar disorder, depression, and schizophrenia] and genes encoding drug targets. We conducted drug enrichment analyses incorporating the novel and biologically specific GSA-MiXeR tool. We conducted multiple molecular trait analyses using large-scale transcriptomic and proteomic datasets sampled from brain and blood tissue. This included the novel use of the UK Biobank proteomic data for a proteome-wide association study of psychiatric disorders. With the accumulated evidence, we prioritize potential drug targets and compounds for each disorder. We reveal candidate drug targets associated with a single or multiple disorders that implicate glutamate signaling. Drug prioritization indicated genetic support for psychotropic medications, including several top-ranked antipsychotics for schizophrenia. We also observed genetic support for commonly used psychotropics for psychiatric treatment (e.g., clozapine, duloxetine, and lithium). Revealed opportunities for drug repurposing included cholinergic drugs for ADHD, estrogen modulators for depression, and matrix metalloproteinases for ADHD and depression. Our findings indicate the genetic liability to schizophrenia is associated with reduced brain and blood expression of CYP2D6, a gene encoding a metabolizer of drugs and neurotransmitters, suggesting a genetic risk for poor drug response and altered neurotransmission. Our extensive analyses highlight the utility of genetics for informing drug development and repurposing for psychiatric disorders, providing novel opportunities for improving patient outcomes. Depicted is the series of analyses conducted to generate a list of prioritized drug targets and compounds. First pairings of genome-wide association study (GWAS) traits with drugs are generated using enrichment analyses. Next, a series of molecular trait analyses is conducted to generate and rank a list of potential drug targets for each GWAS trait. Finally, enrichment and molecular trait results are combined to generate a ranked list of prioritized drugs for each GWAS trait based on supporting genetic evidence. ADHD = Attention deficit hyperactivity disorder, BIP = Bipolar disorder, DEP = Depression, SCZ = Schizophrenia, DBP = Diastolic blood pressure, T2D = Type 2 diabetes, RNA = ribonucleic acid, XWAS = both transcriptome and proteome-wide association studies, MR = Mendelian randomization, coloc = colocalization.

Humans

Liquid preparations for oral administration.

Liquids are easier to swallow and act more quickly than solid dosage forms, but may be unpalatable and relatively unstable. Solutions contain dissolved drugs and may be difficult to formulate or to make palatable; suspensions are usually more pleasant to take but accuracy of dosing may be affected by settling of drug particles. The dose of a drug in liquid and solid form may differ because different drug compounds are often used. Liquids contain many additives which can give rise to adverse affects in the patient.

Chemistry, Pharmaceutical