SEARCH · PubMed Health

Results for “Azabicyclo Compounds”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources

PubMed1994

Zopiclone as a preoperative night hypnotic: a double-blind comparison with temazepam and placebo.

We have examined the hypnotic effects of zopiclone 7.5 mg and temazepam 20 mg compared with placebo in a double-blind, randomized, clinical study of 60 patients on the night before operation. Evaluation was both subjective (visual analogue scales and a sleep questionnaire), to measure the quality of sleep, and objective (critical flicker fusion, object recall and paired associates tasks), to measure residual impairment. We found that zopiclone was an effective single-dose hypnotic with similar residual effects to the benzodiazepine and it may therefore provide a suitable alternative to benzodiazepines.

Adolescent↗

PubMed2025

Rapid replacement of blaKPC variant in ST11 carbapenem-resistant and hypervirulent Klebsiella pneumoniae contributed to ceftazidime/avibactam resistance during severe in vivo infection.

OBJECTIVES: Hypervirulent ceftazidime/avibactam (CAZ/AVI)-resistant Klebsiella pneumoniae (Kp) has emerged; however, its dynamic within-host evolution and competitive features are uncharacterized. This study aimed to clarify the systematic microevolution characteristics of the rapid transformation of blaKPC variants during long-term infection. METHODS: Thirty-nine Kp strains were isolated from a single patient with severe recurrent osteomyelitis during a 2-year period. Whole-genome sequencing and in vitro evolution assay was performed. Microbiological characteristics were examined through antimicrobial susceptibility testing, plasmid stability, growth curve, in vitro competition and Galleria mellonella larvae lethality assays. RESULTS: Among all the clinical Kp isolates, 37 were carbapenem-resistant Kp (CRKP), including 25 CAZ-/AVI-resistant Kp. All isolates belonged to the ST11-K47. During in vivo evolution, the blaKPC variant and its amplification emerged. Twenty-four isolates (24/39, 61.5%) harboured a novel blaKPC variant, blaKPC-144. All five Kp isolates carried blaKPC-2 in 2021. Surprisingly, 24 blaKPC-144-harbouring isolates (70.6%, 24/34) and 10 blaKPC-2-harboring isolates were identified in 2023, indicating rapid changing of blaKPC. Kp4 carried two copies of blaKPC-2, and Kp10-1 exhibited a 1.94-fold increase in the blaKPC-144 copy number. Similarly, in vitro, the blaKPC copy number increased upon exposure to low CAZ/AVI concentrations. However, at higher concentrations (4/1 mg/L), the blaKPC copy number increased significantly, and blaKPC mutations emerged simultaneously. The competition assay indicated that the blaKPC-144-harboring isolates exhibited a superior competitive capacity. CONCLUSIONS: The blaKPC amplification and mutation emerged simultaneously or sequentially during in vivo and in vitro evolution. Kp isolates harbouring blaKPC-144, conferring resistance to CAZ/AVI, exhibited a competitive advantage, promoting the rapid replacement of blaKPC-2.

Klebsiella pneumoniae↗

PubMed2025

Mechanisms of resistance to ceftazidime/avibactam in mutants derived in vitro from Klebsiella pneumoniae producing OXA-48-like enzymes.

OBJECTIVES: To generate in vitro ceftazidime-avibactam-resistant mutants derived from Klebsiella pneumoniae producing OXA-48 or OXA-48 derivatives OXA-131 and OXA-232 carbapenemases, to define their antimicrobial susceptibility phenotype and to analyse mutations potentially involved in resistance to ceftazidime-avibactam. METHODS: Mutants were obtained by plating overnight bacterial cultures on Mueller-Hinton agar plates containing increasing concentrations of ceftazidime-avibactam (0.5/4-32/4 mg/L). MICs were determined using Sensititre™ DKMNG panels. Whole-genome sequencing of 8 parental strains and 31 mutant derivatives was performed with Illumina. RESULTS: All parental strains were susceptible to ceftazidime-avibactam (MIC ≤ 0.5/4-2/4 mg/L) and either susceptible or resistant to meropenem (MIC 0.5 to >16 mg/L) and imipenem (MIC ≤ 0.5 to >16 mg/L). MICs of ceftazidime-avibactam for the mutants increased up to 4 to >16 mg/L, while MICs of meropenem and imipenem for most mutants either increased up to >16 mg/L or remained unchanged. Whole-genome sequencing of the mutants identified alterations in genes coding for proteins related to AcrAB-TolC (AcrB, AcrR), PBPs (PBP2, PBP3), porins (OmpK36, EnvZ) or the stress or stringent responses (RseB, CpxA, SpoT). No mutations were detected in genes coding for OXA-48-like enzymes or other β-lactamases. CONCLUSIONS: Ceftazidime-avibactam can select in vitro mutants of OXA-48-like carbapenemase-producing K. pneumoniae resistant to this combination and, in some cases, also to carbapenems. No mutations related to ceftazidime-avibactam resistance were found in genes coding OXA-48-like enzymes, but they were detected in genes related to active efflux, PBPs, permeability or proteins of the stress and stringent responses.

Ceftazidime↗

PubMed2025

Comparative in vitro activity of ceftazidime-avibactam plus aztreonam and the fixed combination aztreonam/avibactam against multidrug-resistant Pseudomonas aeruginosa.

BACKGROUND AND OBJECTIVES: MDR Pseudomonas aeruginosa is difficult to treat, despite some new beta-lactam/beta-lactamase inhibitors. A combination of ceftazidime-avibactam and aztreonam (CAZ/AVI + AZT) is frequently used to treat Gram-negative bacteria expressing metallo-beta-lactamases. A fixed combination of aztreonam/avibactam was recently licenced for use in Europe, but it remains unknown whether there are differences between both options for use against P. aeruginosa. This study evaluates the comparative in vitro efficacy of the fixed combination aztreonam/avibactam compared to the three antibiotics CAZ/AVI + AZT against clinical MDR P. aeruginosa isolates. METHODS: MICs for aztreonam/avibactam and CAZ/AVI + AZT were determined in 38 MDR P. aeruginosa isolates recovered from routine diagnostics using broth microdilution with checkerboard assays in triplicates as the reference method. Fractional inhibitory concentration (FIC) indices were calculated. Whole-genome sequencing was performed on all isolates. RESULTS: At a fixed ceftazidime concentration of 8 mg/L (EUCAST breakpoint), 25 isolates exhibited lower MICs for CAZ/AVI + AZT compared to aztreonam/avibactam alone in microdilution assays. On FIC analysis, additive and synergistic effects were seen in 28 and 2 cases, respectively. Verona integron-encoded metallo-beta-lactamase (VIM) was the most prevalent carbapenemase (21/38 isolates), followed by Imipenemase (IMP, 4/38) and New Delhi metallo-beta-lactamase (NDM, 2/38). Lower MICs were observed for the combination CAZ/AVI + AZT in isolates carrying VIM-2 as compared to VIM-1. CONCLUSIONS: In vitro testing of CAZ/AVI + AZT revealed increased in vitro susceptibility among MDR P. aeruginosa isolates in comparison to the fixed combination of aztreonam/avibactam.

Pseudomonas aeruginosa↗

PubMedDate not supplied

Analysis of zopiclone (Imovane) in postmortem specimens by GC-MS and HPLC with diode-array detection.

A 26-year-old black female was found dead at home. Her mouth was covered with a fluid containing chalky particles. Empty strips of Imovane (zopiclone) and an empty bottle of Fortal (pentazocine) were also found. No urine was available at autopsy. Screening of postmortem blood and stomach contents with enzyme-multiplied immunoassay technique (EMIT) detected only caffeine. Further screening using routine high-performance liquid chromatography (HPLC) with diode-array detection and gas chromatography (GC) with mass spectrometric detection revealed the presence of large amounts of pentazocine in the blood and stomach contents. In the HPLC chromatogram, a second peak that was only partially resolved from the solvent front was observed. Thin-layer chromatography demonstrated the presence of zopiclone, but optimized HPLC and GC conditions had to be used for proper identification and quantitation. This case illustrates the fact that zopiclone can be easily overlooked during routine forensic screening.

Adult↗

PubMedDate not supplied

Two cases of fatal zopiclone overdose.

Two cases of death due to the ingestion of zopiclone are presented. Quantitative determinations of zopiclone yielded 1.4-3.9 mg/L in the blood, 0.81 and 8.7 mg/kg in the liver, and 13.5 and 133 mg in the stomach contents. Drug concentrations were interpreted relative to the case findings, published data, and a limited evaluation of therapeutic concentrations found in two cases of therapeutic zopiclone use. Zopiclone was extracted from buffered blood or digested liver or both with n-butyl chloride and analyzed by high-performance liquid chromatography with ultraviolet detection. Liver samples were digested at pH 7 to avoid zopiclone decomposition.

Adult↗

PubMedDate not supplied

Zopiclone poisoning.

Explore the source record for details and available documents.

Azabicyclo Compounds↗

PubMedDate not supplied

Detection of 2-amino-5-chloropyridine in urine as a parameter of zopiclone (Imovane) intake using HPLC with diode array detection.

A qualitative screening technique was developed for the detection of 2-amino-5-chloropyridine, a newly identified decomposition product of zopiclone and metabolites after alkaline hydrolysis of urine samples. The method was elaborated using a standard operation procedure (Merck Tox Screening System), combining a solid-phase extraction with reversed-phase high-performance liquid chromatography and diode array detection. The limit of detection, expressed as zopiclone concentrations in spiked urine, was found to be 0.5 microg/mL. Field urine samples from a volunteer were positive for 2-amino-5-chloropyridine until 16 h after ingestion of one therapeutic dose of Imovane (7.5 mg zopiclone).

Administration, Oral↗

PubMed1977

Carcinogenic activity of petasitenine, a new pyrrolizidine alkaloid isolated from Petasites japonicus Maxim.

The carcinogenic activity of petasitenine, a new pyrrolizidine alkaloid isolated from young flower stalk of Petasites japonicus, was studied in ACI rats. All rats that had received a 0.05% solution of petasitenine in drinking water died or were killed in moribund condition 72 days after the start of experiment. They showed necrosis, hemorrhage, and remarkable proliferation of the bile ducts in the liver. In another group that had received a 0.01% solution, 8 of 10 animals surviving beyond 160 days developed tumors in the liver, i.e., hemangioendothelial sarcomas in 5 rats and liver cell adenomas in 5 rats, 2 of which simultaneously developed hemangioendothelial sarcomas. No tumors were observed in the livers of the control animals.

Animals↗

PubMed1987

Behavioral pharmacology of zopiclone.

The pharmacological properties of zopiclone, a cyclopyrrolone derivative, have been studied in comparison with diazepam, nitrazepam, and flurazepam, on behavioral tests in mice and rats, including open-field activity, Skinner box conflict test, hyperemotionality and muricidal behavior of olfactory bulbectomized or raphectomized rats, pentetrazol or electroshock convulsions, inclined screen, rotarod, and thiopental-, ether-, or ethanol-induced anesthesia. Zopiclone exhibited pharmacological properties qualitatively similar to those of benzodiazepines especially in conflict, aggressivity, and pentetrazol-induced convulsion tests. On the other hand, its myorelaxant activity was somewhat weaker than that of the reference drugs. The pharmacological effects of zopiclone were of short duration.

Aggression↗

PubMed1987

Dose-response effects of zopiclone on night sleep and on nighttime and daytime functioning.

Six normal volunteers, aged 20 to 39 years, underwent 2 adaptation nights and three sessions of 2 consecutive experimental nights and days at 1-week intervals, according to a latin-square design. In the three sessions, subjects received either zopiclone, 3.75 mg or 7.5 mg, or placebo at 2215 h in a double-blind protocol. On nights 1 and 2 of each session, subjects were continuously monitored polygraphically, except for a 45-min provoked wake episode 135 min after sleep onset on night 2. Degree of daytime somnolence was assessed during day 1 by means of a multiple sleep latency test (MSLT) and performance evaluation was carried out during night 2 (0000 h) and day 2 (800 h and 1200 h) by means of a battery of four tests. NREM sleep stages 3 and 4 increased significantly after 3.75 mg and 7.5 mg zopiclone (p less than 0.05). No significant differences between placebo and 3.75 mg and 7.5 mg zopiclone were found at any time in the MSLT. Two performance tests (eye-hand coordination test and choice reaction time test) showed a highly significant impairment (p less than 0.01) at 0000 h with 7.5 mg zopiclone; one test (eye-hand coordination test) showed a significant impairment (p less than 0.05) at 0800 h also with 7.5 mg zopiclone and none at 1200 h. From a subjective point of view, depth and quality of sleep were improved, whereas number of awakenings and feeling on awakening were not modified. Side effects (bitter taste, jitteriness, difficulty to concentrate) were reported only with 7.5 mg zopiclone.

Adult↗

PubMed1987

Efficacy of zopiclone in middle age.

Effects of zopiclone (5.0, 7.5, and 10 mg) on sleep and on performance were studied in middle-aged subjects. Zopiclone (5.0-10.0 mg) reduced awake activity and the number of awakenings, and increased the duration of stage 2 sleep. The appearance of REM sleep was delayed, but this effect was without reduction over the whole night. There were no impairments in the digit symbol substitution test when zopiclone was compared with placebo, although there were less substitutions with 10.0 mg than with 5.0 mg. Symbol copying and choice reaction time were unaltered. Zopiclone would appear to be a useful hypnotic for those involved in skilled work. Based on the results obtained in healthy volunteers, the 5.0 mg dose would be appropriate for many; if in insomniac patients, 7.5 mg was needed, then it is likely to be free of undue impairment of performance the next day.

Azabicyclo Compounds↗

PubMed1987

Effect of zopiclone and diazepam on ventilatory response in normal human subjects.

The effects of equipotent, single intravenous doses of zopiclone (7.5 mg) and diazepam (10 mg) on ventilatory responses in healthy volunteers (aged 40 to 60 years) were investigated in a randomized, double-blind cross-over study. Drug injections and subsequent tests were separated by a washout period of at least 3 days. The effects on ventilatory responses were evaluated by measuring nonstimulated tidal volume, breathing frequency, and minute ventilation before and after injection of the test medications. The PO2, PCO2, pH, and base excess of arterial capillary blood, as well as blood pressure and heart rate, were measured during the test sessions. A classical rebreathing Krogh spirometer test was carried out starting with a 7% CO2 level. Total ventilation was calculated for the rebreathing period. The intravenous administration of 10 mg of diazepam induced a moderate but significant reduction in the CO2-stimulated ventilatory responses in normal subjects. This effect was not observed after intravenous injection of 7.5 mg zopiclone. Zopiclone induced an increase in respiratory frequency. Both substances elicited a similar moderate decrease in arterial blood pressure.

Azabicyclo Compounds↗

PubMed1987

Zopiclone and nitrazepam: a multicenter placebo controlled comparative study of efficacy and tolerance in insomniac patients in general practice.

The efficacy and tolerance of zopiclone were compared with nitrazepam and placebo in a multicenter double-blind parallel-group study in insomniac patients. Following a 7-day placebo washout period, 99 patients (age range 20 to 69 years) received oral capsules of 7.5 mg zopiclone or 5 mg nitrazepam or placebo for 2 weeks. During the fourth week all patients received placebo treatment. Sleep assessments by the patients showed that, compared with placebo, zopiclone and nitrazepam improved all sleep measures of efficacy from the first night and that effectiveness was maintained throughout treatment. The physicians global assessment of efficacy also favored zopiclone and nitrazepam over placebo treatment. Subjective morning drowsiness during treatment was significantly less for zopiclone than for either nitrazepam or placebo and represents a clear advantage for ambulatory patients. No rebound insomnia was evident during a 7 day post-treatment withdrawal period for either zopiclone or nitrazepam. Tolerance was good for all treatments.

Adult↗

PubMed1987

Zopiclone versus nitrazepam: a double-blind comparative study of efficacy and tolerance in elderly patients with chronic insomnia.

A randomized, double-blind, comparative trial of zopiclone versus nitrazepam was conducted in 74 geriatric chronic insomniac patients. Following a 7-day wash-out period, two parallel groups, successively received a placebo for 7 days, then either 7.5 mg zopiclone or 5 mg nitrazepam for another 7-day period. Efficacy on sleep was assessed by a sleep analogue scale and the Spiegel Sleep Questionnaire, residual effects by psychometric tests and tolerance by a standardized question, as well as by clinical and laboratory tests. Zopiclone and nitrazepam were more active than placebo on all tests of efficacy. In contrast with nitrazepam, zopiclone was devoid of effect on neurological function. In addition, the condition on awakening was better with zopiclone.

Aged↗

PubMed1987

Effects of flurazepam and zopiclone on the performance of chronic insomniac patients: a study of ethanol-drug interaction.

Three groups of ten middle-aged insomniac patients were treated with placebo, flurazepam, or zopiclone for 12 consecutive days in a study designed to compare the residual daytime effects of long-acting flurazepam and short-acting zopiclone on a variety of cognitive and motor tasks. These effects were examined independently and in combination with ethanol effects. The effects of the drugs on sleep parameters were also subjectively assessed by means of questionnaires during treatment and withdrawal. The study demonstrated persistent performance effects with flurazepam. Testing at the end of the treatment period showed that movement time was impaired in the flurazepam treated group. Flurazepam also enhanced the increment of movement time produced by ethanol. One subject became severely confused when given ethanol after using flurazepam for 12 days. None of these effects were found with zopiclone. The rapid elimination of zopiclone may account for these findings.

Adult↗

PubMed1991

Postmarketing surveillance of zopiclone in insomnia: analysis of 20,513 cases.

The subjective response to the prescription drug zopiclone, an hypnotic agent belonging to the cyclopyrrolone family, was assessed under the usual conditions of prescription of an hypnotic in general practice. The study included 20,513 insomniac outpatients with at least two of the following symptoms: sleep onset latency longer than 1 hour, more than two nocturnal awakenings, early morning awakening 1 hour or more before scheduled time, total sleep time of less than 6 hours, complaint of tiredness on awakening. Insomniac patients were treated with zopiclone and followed for 21 consecutive days within the context of a follow-up surveillance study. The population was predominantly female (62.6%), and the mean age was 52.3 years. The dosage of zopiclone prescribed at the inclusion visit was 7.5 mg per day in 87.5% of the cases and 3.75 mg per day in 10.5%. A total of 93.8% of the patients completed the survey. Spiegel questionnaire improved during the 21-day survey, and 9.2% of the patients reported at least one adverse event that led to treatment discontinuation in only 2.8% of the population. No serious or unexpected adverse events were reported.

Adolescent↗

PubMed1993

Comparison of the effect of zopiclone and brotizolam on sleep EEG by quantitative evaluation in healthy young women.

We studied the effect of brotizolam (BRO) (0.25 mg) and zopiclone (ZPC) (7.5 mg) on the sleep electroencephalograms (EEG) of seven healthy young women (ages 20-21 years). In addition to conventional sleep scoring, we performed spectral analysis of EEG wave forms using the Fast Fourier Transformation (FFT) method. Four weeks following two consecutive polysomnographic recordings with placebo administration (for baseline data), polysomnography with BRO or ZPC administration was performed on the subjects who were then crossed over to polysomnography with ZPC or BRO, respectively, 1 week later. Total rapid eye movement (REM) time was decreased on the ZPC and BRO nights and REM latency was prolonged on the ZPC night compared with baseline (BL) night. Other parameters, however, were not significantly different between the drug nights and the BL night. There were also no differences in standard scoring results between both drug nights. FFT analysis revealed significant differences in total power density percentage and mean power density percentage in both nonrapid eye movement (NREM) and REM sleep between ZPC and BRO nights and between both drug nights compared to the BL night. Total power density and mean power density per epoch showed significant decreases in the theta band (6.0-8.0 Hz) and sigma band (12.0-14.0 Hz) on the ZPC night versus the BRO night or BL night during specific NREM periods. The results of this study corroborate previous reports that suggest computer-aided quantitative electroencephalography aids in differentiating specific effects of hypnotics and other central-nervous-system-acting agents on the sleep EEG.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗