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The Japanese Journal of Antibiotics Feb 1976
Clinical Trial Comparative Study
Topics: Acute Disease; Adolescent; Anti-Infective Agents, Urinary; Clinical Trials as Topic; Cystitis; Drug Evaluation; Escherichia coli; Female; Humans; Male; Nicotinic Acids; Piperazines; Pregnancy; Pyrimidines; Pyrrolidines; Recurrence
PubMed: 772246
DOI: No ID Found -
Molecular Pharmacology May 1993Four piperazinoquinolone antibacterial drugs (norfloxacin, ciprofloxacin, enoxacin, and pipemidic acid), known to be gamma-aminobutyric acid (GABA) antagonists, fully...
Indomethacin/ibuprofen-like anti-inflammatory agents selectively potentiate the gamma-aminobutyric acid-antagonistic effects of several norfloxacin-like quinolone antibacterial agents on [35S]t-butylbicyclophosphorothionate binding.
Four piperazinoquinolone antibacterial drugs (norfloxacin, ciprofloxacin, enoxacin, and pipemidic acid), known to be gamma-aminobutyric acid (GABA) antagonists, fully reversed the inhibitory effect of GABA on [35S]t-butylbicyclophosphorothionate ([35S] TBPS) binding to rat brain membranes in vitro. Twelve indomethacin/ibuprofen-like arylalkanoic acid (AAA) anti-inflammatory drugs alone had no effect on [35S]TBPS binding, or on its inhibition by GABA, but potentiated the GABA-antagonistic effects of the four quinolones. Felbinac (4-biphenylacetic acid) was most potent in this respect (EC50 = 110 nM, together with 5 microM norfloxacin), followed by flurbiprofen > anirolac > metiazinic acid > tolmetin = ketoprofen = fenbufen = indomethacin > fenoprofen > ibuprofen = (+)-naproxen = sulindac. Other anti-inflammatory analgesic drugs, including aspirin, diclofenac, diflunisal, meclofenamic acid, mefenamic acid, nambumetone, phenacetin, piroxicam, and phenylbutazone, failed to potentiate the GABA-antagonistic effect of norfloxacin. Felbinac (1 microM) increased the GABA-antagonistic potencies of norfloxacin and enoxacin about 26-fold, while increasing those of ciprofloxacin and pipemidic acid 7-fold and 2.3-fold, respectively. Using subsaturating concentrations of the four quinolones, concentration-response curves for felbinac yielded EC50 values ranging from 110 nM with 5 microM norfloxacin to 1.3 microM with 100 microM pipemidic acid. Three other piperazinoquinolone antibacterial agents (amifloxacin, difloxacin, and fleroxacin) and four nonpiperazinoquinolone anti-bacterial agents (oxolinic acid, cinoxacin, nalidixic acid, and piromidic acid) were much weaker GABA antagonists and were not significantly potentiated by felbinac. All other known GABAA receptor blockers tested, including R 5135, pitrazepin, bicuculline, SR 95531, strychnine, D-tubocurarine, thebaine, securinine, theophylline, and caffeine, were not potentiated by felbinac. Our results suggest that norfloxacin and related piperazinoquinolones, acting at GABAA receptors, may induce a high affinity binding site for indomethacin/ibuprofen-like anti-inflammatory agents (the AAA site) that, when occupied, reciprocally increases the affinities of the quinolones for GABAA receptors. The AAA binding site may be a new site in the GABAA receptor complex.
Topics: 4-Quinolones; Animals; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Brain; Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Drug Synergism; Female; GABA Antagonists; In Vitro Techniques; Male; Radioligand Assay; Rats; Rats, Sprague-Dawley; Receptors, GABA-A
PubMed: 8388990
DOI: No ID Found -
Spectrochimica Acta. Part A, Molecular... Feb 2020The self-association of fluoroquinolones (FQ) in water would play a relevant role in their translocations across lipid membranes. Triplet excited states of these drugs...
The self-association of fluoroquinolones (FQ) in water would play a relevant role in their translocations across lipid membranes. Triplet excited states of these drugs have been shown as reporters of FQ self-association using laser flash photolysis technique. A study using low-temperature phosphorescence technique was performed with quinolone derivatives such as enoxacin (ENX), norfloxacin (NFX), pefloxacin (PFX), ciprofloxacin (CPX, ofloxacin (OFX), nalidixic acid (NLA), pipemidic acid (PPA) and piromidic acid (PRA) to explore emission changes associated with self-associations and to shed some light on the triplet excited state energy (E) discrepancies described in the literature for most of these drugs. The emissions obtained at 77 K in buffered aqueous medium revealed that the amphoteric nature of the quinolones CPX, NFX, PFX, ENX, OFX and PPA must generate their self-associations because a redshift of their phosphorescence maxima is produced by FQ concentrations increases. Hence, this effect was not observed for NLA and PRA or when all quinolones were analysed using ethanol or ethylene glycol aqueous mixtures as glassed solvents. Interestingly, the presence of these organic mixtures produced a blue-shift in the phosphorescence emission maximum of each FQ. Additionally, laser flash photolysis experiments with PRA and the amphoteric quinolone PPA, compounds with the same skeleton but different peripheral substituent, confirm the expected correlations between the amphoteric nature of compounds and their self-associations in aqueous media because the excimer generation was only detected for PPA. Now, the discrepancies described in the literature for the E of FQs can be understood considering that changes of medium polarity or proticity as well as the temperature can considerably modify their E values. Thereby, low-temperature phosphorescence technique, is an effective way to detect molecular self-associations and surrounding changes in quinolones that opens the possibility to evaluate these effects in other drug families.
Topics: Buffers; Dimerization; Fluoroquinolones; Luminescent Measurements; Models, Molecular; Photolysis; Water
PubMed: 31670049
DOI: 10.1016/j.saa.2019.117569 -
The Journal of Antimicrobial... Mar 1986Ofloxacin (9-fluoro-3-methyl-10-(4-methyl-1-piperazynyl)-7-oxo-2,3-dihydro-7 H-pyrido-(1,2,3-de)1,4-benzoxazine-6-carboxylic acid) and enoxacin...
Ofloxacin (9-fluoro-3-methyl-10-(4-methyl-1-piperazynyl)-7-oxo-2,3-dihydro-7 H-pyrido-(1,2,3-de)1,4-benzoxazine-6-carboxylic acid) and enoxacin (1-ethyl-6-fluoro-1,4-dehydro-4-oxo-7-(1-piperazinyl)-1, 8-naphthyridine-3-carboxylic acid) are newly developed pyridone carboxylic acid derivatives with broad and potent antibacterial activities against Gram-negative and Gram-positive bacteria. Antibacterial activities of six pyridone carboxylic acid derivatives, including these two new antibiotics, were examined against Gram-negative bacilli in the presence and absence of ethylenediaminetetraacetic acid (EDTA) or gentamicin. The minimal inhibitory concentrations (MICs) of nalidixic acid, cinoxacin and piromidic acid were reduced by the addition of EDTA or gentamicin. However, the MICs of pipemidic acid, ofloxacin and enoxacin were unaffected. These findings indicated the high permeability of pipemidic acid, ofloxacin and enoxacin through the outer membrane. The effects of EDTA and gentamicin against Serratia marcescens were different from those against other Gram-negative bacilli.
Topics: Anti-Bacterial Agents; Edetic Acid; Enoxacin; Gentamicins; Gram-Negative Bacteria; Microbial Sensitivity Tests; Naphthyridines; Ofloxacin; Oxazines; Pyridones
PubMed: 3084441
DOI: 10.1093/jac/17.3.327 -
Kansenshogaku Zasshi. the Journal of... Jan 1971
Topics: Adolescent; Adult; Child; Child, Preschool; Dysentery, Bacillary; Feces; Female; Humans; Infant; Ketones; Male; Middle Aged; Picolinic Acids; Pyrazoles; Pyrimidines; Shigella dysenteriae
PubMed: 4994343
DOI: 10.11150/kansenshogakuzasshi1970.45.11 -
Journal of AOAC International 1996A previously published liquid chromatographic (LC) method for determining residues of flumequine (FLU) and nalidixic (NAL), oxolinic (OXO), and piromidic (PIR) acids in...
A previously published liquid chromatographic (LC) method for determining residues of flumequine (FLU) and nalidixic (NAL), oxolinic (OXO), and piromidic (PIR) acids in catfish tissue was applied to salmon and shrimp muscle. Identities of all 4 residues in salmon and shrimp were confirmed by gas chromatography/mass spectrometry (GC/MS). The tissue is homogenized with acetone, the acetone extract is defatted with hexane, and the quinolones are extracted into chloroform. The extract is further purified by first partitioning into base and then back-extracting from a solution acidified to pH 6.0. Analytes are determined by LC with simultaneous UV and fluorescence detection. Muscle tissue was fortified with each quinolone at 5, 10, 20, 40, and 80 ng/g. Average recoveries and relative standard deviations (RSDs) for salmon, which represent an average of the 5 levels for each analyte, ranged from 75.9 to 90.8% and from 2.25 to 6.40%, respectively. Average recoveries and RSDs for shrimp ranged from 81.3 to 91.2% and from 7.34 to 10.7%, respectively. Identities of OXO, FLU, NAL, and PIR were confirmed in extracts of salmon and shrimp tissue fortified at 10 ng/g by determination of decarboxylated quinolones by GC/MS. Four diagnostic ions were monitored for OXO, FLU, and PIR, and 5 ions were monitored for NAL. All ion relative abundances were within 10% of those calculated for standard decarboxylated quinolones. Optimum conditions for decarboxylation and GC/MS confirmation are given.
Topics: Animals; Anti-Infective Agents; Decapoda; Drug Residues; Fluoroquinolones; Food Contamination; Gas Chromatography-Mass Spectrometry; Muscles; Nalidixic Acid; Oxolinic Acid; Piromidic Acid; Quinolizines; Reference Standards; Salmon
PubMed: 8823929
DOI: No ID Found -
Mutation Research Feb 2006The purpose of this study was to examine the genotoxicity of quinolone antimicrobials. We investigated the genotoxic potential of eight quinolones, namely nalidixic acid...
The purpose of this study was to examine the genotoxicity of quinolone antimicrobials. We investigated the genotoxic potential of eight quinolones, namely nalidixic acid (NA), pipemidic acid (PPA), oxolinic acid (OA), piromidic acid (PA), enoxacin (ENX), ofloxacin (OFLX), norfloxacin (NFLX) and ciprofloxacin (CPFX), by the in vitro alkaline single-cell gel electrophoresis (comet) assay at pH>13. WTK-1 cells (mutant p53) were treated with each of the eight quinolones at 62.5-1000 microg/mL for 2, 4 and 20 h. NFLX and CPFX significantly induced DNA damage concentration-dependently after 4 and 20 h treatment, but this damage was recoverable. On the other hand, DNA was not damaged in the cells treated with six other quinolones. In the cells treated with NFLX and CPFX for 20 h, DNA migration was compared by the comet assay at pH 10, 12.1 and >13. The comet assay both at pH 12.1 and >13 showed increased DNA migration, but there was no positive response in the comet assay at pH 10. In the in vitro micronucleus (MN) test, WTK-1 cells were treated with each of four quinolones (NA, PPA, NFLX and CPFX) at 15.63-125 microg/mL for 20 h. NFLX significantly increased MNs in the cells, but no changes were noted in the cells treated with three other quinolones. These results suggest that NFLX and CPFX induced DNA single strand breaks (SSBs), and that NFLX-induced SSBs resulted in chromosome aberrations.
Topics: Anti-Infective Agents; Chromosome Aberrations; Comet Assay; DNA Damage; Humans; In Vitro Techniques; Lymphoma; Micronucleus Tests; Mutation; Quinolones; Tumor Suppressor Protein p53
PubMed: 16384725
DOI: 10.1016/j.mrgentox.2005.11.003 -
Journal of Chromatography. A Dec 2008A sensitive liquid chromatography-electrospray tandem mass spectrometry method, combined with solid-phase extraction and a weak cation exchange cartridge cleanup, was...
A sensitive liquid chromatography-electrospray tandem mass spectrometry method, combined with solid-phase extraction and a weak cation exchange cartridge cleanup, was established for twenty quinolone and fluoroquinolone antibiotics (pipemidic acid, flerofloxacin, ofloxacin, pefloxacin, enoxacin, norfloxacin, ciprofloxacin, danofloxacin, enrofloxacin, lomefloxacin, difloxacin, sarafloxacin, gatifloxacin, sparfloxacin, moxifloxacin, cinoxacin, oxolinic acid, nalidixic acid, flumequine, and piromidic acid) in influent, effluent, and river waters. For the various water matrices considered, the overall recoveries were from 64% to 127% except for piromidic acid (27-33%), and no obvious matrix effect was observed. The method detection limits for the twenty target antibiotics in the influent, effluent, and surface water samples were 1.6-50 ng/L, 0.6-50 ng/L, and 0.8-50 ng/L, respectively. This method was applied to analyze residual quinolone and fluoroquinolone antibiotics in wastewater and surface water samples from Beijing, China. Eight antibiotics (12 (pipemidic acid)-1208 ng/L (ofloxacin)) were detected in wastewater, and seven (1.3 (lomefloxacin)-535 ng/L (ofloxacin)) were detected in surface water samples. Gatifloxacin, a 4th generation fluoroquinolone antibiotic, was detected for the first time in influent (111 ng/L), effluent (56 ng/L), and river water (16-42 ng/L).
Topics: Anti-Bacterial Agents; China; Chromatography, Liquid; Fluoroquinolones; Quinolones; Reproducibility of Results; Sensitivity and Specificity; Solid Phase Extraction; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; Water Pollutants, Chemical
PubMed: 19007934
DOI: 10.1016/j.chroma.2008.10.090 -
Veterinary and Human Toxicology 1986The principal bacterial diseases of cultured rainbow trout (Salmo gairdneri) and channel catfish (Ictalurus punctatus), and the antibacterials used in their treatment... (Review)
Review
The principal bacterial diseases of cultured rainbow trout (Salmo gairdneri) and channel catfish (Ictalurus punctatus), and the antibacterials used in their treatment are briefly reviewed. Gram-negative bacteria predominate, and oxytetracycline is effective in treatment of infections induced by them. The only antibacterials now registered by the US Food and Drug Administration are sulfamerazine for the treatment of furunculosis in trout, and oxytetracycline for the treatment of furunculosis in salmonids and Aeromonas and Pseudomonas infections in salmonids and catfish. Registration 9/50 is now complete for the potentiated sulfonamide Romet-30 for controlling furunculosis in salmonids. Studies on the metabolism of antibacterials in fishes are limited, and are primarily concerned with tissue residue and elimination rate.
Topics: Animals; Bacterial Infections; Catfishes; Fish Diseases; Ictaluridae; Nitrofurans; Piromidic Acid; Salmonidae; Sulfonamides; Trout
PubMed: 3334692
DOI: No ID Found -
La Clinica Terapeutica Sep 1979
Topics: Adolescent; Adult; Bacterial Infections; Female; Humans; Nicotinic Acids; Piromidic Acid; Pregnancy; Pregnancy Complications, Infectious; Puerperal Disorders; Urinary Tract Infections
PubMed: 535334
DOI: No ID Found