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At least 271 records · Page 15Linked to original sources
PubMed1995

Antioxidant and anti-inflammatory property of Sandhika: a compound herbal drug.

The present study was envisaged to assess the rationality for the use of "Sandhika", a popular Ayurvedic drug in rheumatoid arthritis. This drug, when tested against carrageenan induced paw oedema and cotton pellet granuloma, showed significant anti-inflammatory activity at the dose of 0.25 g/kg body weight. The antioxidant property was assessed by determining cumene hydroperoxide (CHP) induced lipid peroxidation and reduced glutathione content in rat liver homogenate (in vitro). Experiments show the significant protection against lipid peroxidation at the dose of 80 micrograms/ml, measured as reduction in the level of malondialdehyde (MDA) induced by 1.5 mM cumene hydroperoxide (CHP). This effect was accompanied by the maintained reduced glutathione (GSH) content in drug treated rats. Oral treatment of drug up to 2 g/kg body weight for 15 days did not show any rise in serum transaminases (SGOT and SGPT). The results suggest that "Sandhika" which is an indigenous drug for inflammation with no detectable adverse effect, might be acting through scavenging the free radicals.

Animals↗
PubMed2026

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↗
PubMedDate not supplied

Immediate-type allergy to drugs and related compounds: evaluation and management.

Adverse drug reactions (ADR) constitute a major health issue in outpatient and inpatient clinical settings. An allergic drug reaction is an immunologically mediated adverse drug reaction that exhibits specificity and recurrence on re-exposure to the offending and/or cross-reactive compound(s). Diagnosis of drug allergy is difficult, as a broad spectrum of different drugs can elicit various immune-mediated diseases with distinct (sometimes unclear) pathomechanism, the exact structure (epitope) that causes the reaction is frequently unknown, the presence of an in vitro or in vivo test results might not be predictive of a clinical situation, and the gold standard or reference test for diagnosis, the drug challenge, is a complicated and sometimes dangerous endeavour. Nevertheless, during the past few years serious attempts have been made to standardise and validate in vitro and in vivo techniques for the diagnosis of drug allergy. New techniques, e.g. flow-assisted analysis of in vitro basophil activation, are replacing older ones like histamine release for immediate-type hypersensitivity reactions. However, additional comprehensive studies are required to further validate the technique and allow its entrance in mainstream diagnostic use, particularly for non-IgE-mediated hypersensitivity. This review attempts to summarize the major causes of immediate hypersensitivity reactions to drugs and related compounds. Special attention is paid to the diagnostic and therapeutic management of this common iatrogenic complication.

Drug Hypersensitivity↗
PubMed1996

Outsourcing inpatient i.v. compounding: expense and medication error implications.

A quasi-experiment was conducted to evaluate differences in intravenous (i.v.) drug compounding costs and frequency of medication administration errors of omission before and after outsourcing the hospital's i.v. admixture refill program to an alternate site home i.v. infusion pharmacy. As part of the outsourcing changes, the pharmacy redeployed an i.v. admixture technician to do i.v. recycling on the nursing units. The study was a single subject, pretest, posttest (within subjects) design using an observer. The independent variables were outsourcing and having an i.v. recycling technician. The dependent variables were medication errors of omission and costs directly associated with the two i.v. programs. A statistically significant reduction in the frequency of medication administration errors of omission was associated with implementation of the outsourcing program. In addition, first year expenses were reduced by an estimated $86,356.

Clinical Pharmacy Information Systems↗
PubMed2003

High-throughput cytochrome p450 inhibition assays by ultrafast gradient liquid chromatography with tandem mass spectrometry using monolithic columns.

A generic method employing ultrafast liquid chromatography with tandem mass spectrometry (LC/MS/MS) was developed and employed for routine screening of drug candidates for inhibition of five major human cytochrome p450 (CYP) isozymes, CYP3A4, CYP2D6, CYP2C9, CYP2C19, and CYP1A2. The method utilized a monolithic silica rod column to allow fast flow rates to significantly reduce chromatographic run time. The major metabolites of six CYP-specific probe substrates for the five p450 isoforms were monitored and quantified to determine IC(50) values of five drug compounds against each p450 isozyme. Human liver microsomal incubation samples at each test compound concentration were combined and analyzed simultaneously by the LC/MS/MS method. Each pooled sample containing six substrates and an internal standard was separated and detected in only 24 seconds. The combination of ultrafast chromatography and sample pooling techniques has significantly increased sample throughput and shortened assay turnaround time, allowing a large number of compounds to be screened rapidly for potential p450 inhibitory activity, to aid in compound selection and optimization in drug discovery.

Chromatography, Liquid↗
PubMed2001

The popliteal lymph node assay: a tool for predicting drug allergies.

A considerable number of drugs is able to induce systemic hypersensitivity in man. Systemic hypersensitivity can be drug- or autoantigen-specific, but in either case a complex of immunological processes and predisposing factors are involved and it is rarely if ever noticed in standard toxicity testing. The popliteal lymph node assay (PLNA) is regarded a suitable test to screen for the immunostimulating ability of a chemical, which may indicate its immunosensitizing potential. The most simple, primary PLNA measures popliteal lymph node hyperplasia after subcutaneous injection of a chemical into the footpad of the hindpaw of a mouse or rat. In order to assess the involvement of T cells, and hence immunosensitizating potential of a chemical, anamnestic immune reactions to a chemical or its metabolite can be measured in previously exposed (and sensitized) animals or in naive animals that received an adoptive transfer of syngeneic T cells from previously exposed animals. In the recently introduced modified PLNA, defined reporter antigens TNP-OVA (T cell-dependent antigen) and TNP-Ficoll (T cell-independent antigen) are used to distinguish between sensitizing and non-sensitizing (IgG1-response or not to TNP-Ficoll, respectively) and between mere inflammatory and complete innocent (no IgG1-response to TNP-Ficoll and an IgG1-response or not to TNP-OVA, respectively) drugs. Results with about 130 compounds (drugs and environmental pollutants) with the various types of the PLNA show a good correlation with documented immunostimulating (both autoimmunogenic and allergic) potential and no false negative chemicals were detected if metabolism was considered. The PLNA awaits further validation before this test can be recommended as a tool for prediction of drug allergy.

Allergens↗
PubMed1985

Regional hospital pharmacy information index.

An index system was developed that provides participating hospitals with an up-to-date list of regionally available written materials used in hospital pharmacy practice. Eight acute-care hospitals agreed to participate in developing the index to avoid duplication of effort in producing original materials. A regional drug information center agreed to maintain the index and serve as the central repository for the materials. Newsletters and bulletins were given high priority for coverage by the system, followed by drug monographs and directed studies and residency projects. A three-year back-index period was set for most categories to ensure that the index was current. Only active entries were listed for investigational drug lists, i.v. drug administration monographs, and extemporaneously compounded drug products. Other categories were drug administration policies, unusual drug information requests, and patient-oriented drug information. The representatives provided the relevant materials from their institutions, and it was categorized and indexed. The index was entered on a word processor, which permits efficient updating. The index has been useful to the participating hospital pharmacy departments. As the system is tested through use, it will be evaluated formally and refined.

Abstracting and Indexing↗
PubMed2003

Determination of content uniformity and distribution characteristics of an investigational drug in its tablets dosage form and granule by ICP-AES.

An investigational drug (A) in its calcium salt form has been developed as the tablet dosage form. Monitoring drug distribution and uniformity in granules and tablets during early stage formulation/process development is critical for drug product quality control and process robustness. In this report, an efficient and reliable analytical method for monitoring drug compound A uniformity and distribution has been developed by analyzing calcium, the counter ion of the drug substance, by Inductively Coupled Plasma Atomic Emission Spectrometer (ICP-AES). In this method, calcium in compound A granule and tablet samples was digested with 1 M hydrochloric acid by heating at 90 degrees C for 2 h. The resulting suspension was centrifuged, and the supernatant was directly aspirated into an ICP-AES. This method has been validated to demonstrate satisfactory precision, accuracy, specificity and sensitivity. Finally, this method has been used to analyze sieve fraction granules and tablets of drug compound A. The data generated were highly comparable to those by validated HPLC methods (UV method can not be applicable due to significant bias). In comparison with HPLC methods, this method demonstrates a significantly improved efficiency with very short analysis time (1 min per sample), and can be used as an excellent alternative for UV and HPLC methods to support formulation screening.

Drugs, Investigational↗
PubMed1988

[Analysis of residues of organochlorine compounds in plant drugs. 3. Identification of residues of polychlorobiphenyl compounds by comparison of gas chromatography on packed and capillary columns and GCMS coupling].

The identification of residues of polychlorinated biphenyls in a test sample of Flores Chamomillae could be achieved by the retention behavior at gas chromatographic analyses on packed and capillary columns compared with reference standard Clophen A 60, respectively as well as well by capillary GC/MS using single ion monitoring of substance-characteristic ion mass.

Chromatography, Gas↗
PubMed2006

Acyclic nucleoside analogues as inhibitors of Plasmodium falciparum dUTPase.

We report the discovery of novel uracil-based acyclic compounds as inhibitors of deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase), an enzyme involved in nucleotide metabolism that has been identified as a promising target for the development of antimalarial drugs. Compounds were assayed against both P.falciparum dUTPase and intact parasites. A good correlation was observed between enzyme inhibition and cellular assays. Acyclic uracil derivatives were identified that showed greater or similar potency and in general increased selectivity compared to previously reported inhibitors. The most active compound reported here against the P. falciparum enzyme had a K(i) of 0.2 microM. Molecular modeling studies provided a good rationale for the observed activities. Preliminary ADME studies indicated that some of the lead compounds are drug-like molecules. These compounds are useful tools for further investigating P. falciparum dUTPase for the development of much-needed novel antimalarial drugs.

Animals↗
PubMedDate not supplied

TLC fractionation and visualization of selected phenolic compounds applied as drugs.

Sixteen visualizing agents, thirteen of which were a group of alkacemetric indicators were used for the detection of selected drugs (being phenolic compounds): adrenaline, dopamine, phenylephrine, metaraminol, fenoterol, and bithionol. Visualizing effects for the drugs investigated after their TLC separation were estimated on silicagel (A), mixture silica gel/kieselguhr (B), and on polyamide (C). The best separations and the most positive visualising effects were obtained on adsorbent A, and the least on absorbent C. On adsorbent A, the most profitable detectability equal to 100 ng, was obtained also for adrenaline, dopamine and fenoterol with the application of basic solution of bromocresol green and brilliant cresyl blue as visualizing agents.

Chromatography, Thin Layer↗
PubMed1984

Are levodopa "drug holidays" justified?

Complete withdrawal of all levodopa compounds "drug holiday" for a period of at least one week in severely disabled, unresponsive Parkinson patients may influence receptor blockade by resensitizing and can alter denervation hypersensitivity. Twenty four patients with 31 holidays were evaluated. Transient improvement was noted in most patients, however significant long term benefit of over 1 years duration occurred in only 6 individuals. In view of the unpredictability and limited responsiveness, drug holiday has not yet been established as a satisfactory treatment for the severe, intractable problems associated with chronic levodopa administration in Parkinson patients. Further trials appear to be warranted.

Humans↗
PubMedDate not supplied

Aqueous solubility prediction of drugs based on molecular topology and neural network modeling.

A method for predicting the aqueous solubility of drug compounds was developed based on topological indices and artificial neural network (ANN) modeling. The aqueous solubility values for 211 drugs and related compounds representing acidic, neutral, and basic drugs of different structural classes were collected from the literature. The data set was divided into a training set (n = 160) and a randomly chosen test set (n = 51). Structural parameters used as inputs in a 23-5-1 artificial neural network included 14 atom-type electrotopological indices and nine other topological indices. For the test set, a predictive r2 = 0.86 and s = 0.53 (log units) were achieved.

Models, Chemical↗
PubMed1997

Inter- and intraspecies polymorphisms in the cholecystokinin-B/gastrin receptor alter drug efficacy.

The brain cholecystokinin-B/gastrin receptor (CCK-BR) is a major target for drug development because of its postulated role in modulating anxiety, memory, and the perception of pain. Drug discovery efforts have resulted in the identification of small synthetic molecules that can selectively activate this receptor subtype. These drugs include the peptide-derived compound PD135,158 as well as the nonpeptide benzodiazepine-based ligand, L-740,093 (S enantiomer). We now report that the maximal level of receptor-mediated second messenger signaling that can be achieved by these compounds (drug efficacy) markedly differs among species homologs of the CCK-BR. Further analysis reveals that the observed differences in drug efficacy are in large part explained by single or double aliphatic amino acid substitutions between respective species homologs. This interspecies variability in ligand efficacy introduces the possibility of species differences in receptor-mediated function, an important consideration when selecting animal models for preclinical drug testing. The finding that even single amino acid substitutions can significantly affect drug efficacy prompted us to examine ligand-induced signaling by a known naturally occurring human CCK-BR variant (glutamic acid replaced by lysine in position 288; 288E --> K). When examined using the 288E --> K receptor, the efficacies of both PD135,158 and L-740, 093 (S) were markedly increased compared with values obtained with the wild-type human protein. These observations suggest that functional variability resulting from human receptor polymorphisms may contribute to interindividual differences in drug effects.

Animals↗
PubMed2005

Comparison of human tracheal/bronchial epithelial cell culture and bovine nasal respiratory explants for nasal drug transport studies.

Ten drug compounds with varying physicochemical properties and transporter substrate specificities were investigated to compare their in vitro permeabilities across bovine nasal respiratory explants and the EpiAirway system, both established models for the assessment of nasal drug absorption. Permeability across the bovine explants and EpiAirway correlated well with the partitioning behavior of compounds whose clogDC values were greater than 0. The permeabilities of all ten compounds were well-correlated between the two tissue models, with the permeability values through the EpiAirway tissues being approximately 10-fold higher than through the bovine explants due to the thickness differences between the models. For more lipophilic compounds, the in vitro permeabilities measured with both tissue systems were also predictive of the reported in vivo nasal bioavailabilities. Deviations from these correlations were observed for compounds reported to be substrates of p-glycoprotein or OCT transporters, and differences were also seen between the permeabilities measured in the tissue models for these compounds. Both models can be used to estimate the systemic bioavailability of moderately lipophilic compounds administered intranasally, while each may have particular advantages or disadvantages in estimating the bioavailability of drug compounds that are subject to local mucosal metabolism or to carrier-mediated uptake or efflux.

Animals↗
PubMed1999

Capillary electrophoresis of natural products-II.

Capillary zone electrophoresis (CZE) and micellar electrokinetic capillary chromatography (MEKC) were used for the separation of widely different compounds from natural materials including compounds from tea, acids from different matrices, flavonoids and alkaloids, toxins and toxicological compounds, proteins and polypeptides, biogenic amines, phenolic compounds in alcoholic beverages, Chinese medicinal drugs, compounds in cells and cell extracts, and miscellaneous other applications. A section dealing with recent reviews related to natural products is also included.

Alkaloids↗
PubMed1998

Multiwavelength spectrophotometric determination of acid dissociation constants of ionizable drugs.

A multiwavelength spectrophotometric approach has been developed to determine acid dissociation constants (pKa values) of sparingly soluble drug compounds. UV absorption spectra of the drug solution are acquired using a versatile device based on a fiber optics dip probe, a light source and a photodiode array (PDA) detector while the PH and the ionic strength of the chemical system is manipulated precisely by means of a commercially available titrator. Target factor analysis (TFA) has been applied to deduce the pKa values from the multiwavelength UV absorption data recorded at different pH values. We have called this multiwavelength approach the WApH technique because the pKa results are determined from changes in Wavelength and Absorbance as a function of pH (WApH). The WApH technique is exemplified by using several pure drugs, namely, niflumic acid, nitrazepam, pyridoxine, quinine and terbutaline. The pKa values obtained agree well with those derived from pH-metric titrations. It has been demonstrated that the WApH technique is able to deduce pKa values with high accuracy even if the absorption spectra of the reacting species are very similar.

Hydrogen-Ion Concentration↗