Pharmacodynamics of Tolerance Development to the Anesthetic and Anticonvulsant Effects of Phenobarbital in Rats

Dingemanse, Jasper; Hameter, Bart M.; Danhof, Meindert

doi:10.1002/jps.2600790305

Cited by 8 publications

(6 citation statements)

References 26 publications

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“… a Because of the low affinity of phenobarbital for apoferritin, it was not possible to obtain a satisfactory estimate of the molar binding enthalpy. b [16]. c [41]. d [42]. e [43]. f [44]. g Calculated using XLOGP3 [45].…”

Section: Resultsmentioning

confidence: 99%

Recognition of Anesthetic Barbiturates by a Protein Binding Site: A High Resolution Structural Analysis

Oakley

Vedula

et al. 2012

PLoS ONE

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Barbiturates potentiate GABA actions at the GABAA receptor and act as central nervous system depressants that can induce effects ranging from sedation to general anesthesia. No structural information has been available about how barbiturates are recognized by their protein targets. For this reason, we tested whether these drugs were able to bind specifically to horse spleen apoferritin, a model protein that has previously been shown to bind many anesthetic agents with affinities that are closely correlated with anesthetic potency. Thiopental, pentobarbital, and phenobarbital were all found to bind to apoferritin with affinities ranging from 10–500 µM, approximately matching the concentrations required to produce anesthetic and GABAergic responses. X-ray crystal structures were determined for the complexes of apoferritin with thiopental and pentobarbital at resolutions of 1.9 and 2.0 Å, respectively. These structures reveal that the barbiturates bind to a cavity in the apoferritin shell that also binds haloalkanes, halogenated ethers, and propofol. Unlike these other general anesthetics, however, which rely entirely upon van der Waals interactions and the hydrophobic effect for recognition, the barbiturates are recognized in the apoferritin site using a mixture of both polar and nonpolar interactions. These results suggest that any protein binding site that is able to recognize and respond to the chemically and structurally diverse set of compounds used as general anesthetics is likely to include a versatile mixture of both polar and hydrophobic elements.

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Section: Resultsmentioning

confidence: 99%

Recognition of Anesthetic Barbiturates by a Protein Binding Site: A High Resolution Structural Analysis

Oakley

Vedula

et al. 2012

PLoS ONE

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“…Since there is theoretical concern that NaPB may have direct effects on brain tissue as a barbiturate antiepileptic drug ( Dingemanse et al, 1989 , Lumley et al, 2021 ), histopathological examination of the brain for fetuses was conducted at the three levels to evaluate for any qualitative changes. The three blocks of the brain prepared as described above were used and carefully thinned to obtain the three levels of planes (the first level [cerebrum 1] included cerebral cortex and caudate/putamen, the second level [cerebrum 2] included cerebral cortex, hippocampus, thalamus, and hypothalamus, and the third level included cerebellum and brain stem along the mid-sagittal plane) homogeneously throughout all animals, which was modified for GD20 from Garman et al (2016) (Supplemental Fig.…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, in our previous verification study for the modified CTA, NaPB was selected as a second reference chemical together with 6-PTU ( Minami et al, 2023 ). However, as PB or NaPB is a highly neuroactive drug ( Dingemanse et al, 1989 , Lumley et al, 2021 ), it is likely to affect brain development ( Diaz and Schain, 1978 , Middaugh et al, 1981 ). Nevertheless, considering that the CTA is not a test for DNT and the purpose of the CTA is to examine the extent to which a mild reduction of maternal TH can affect the TH concentration in offspring, the use of NaPB as a reference chemical with maternal mild TH disruption in the present study would provide useful information.…”

Section: Introductionmentioning

confidence: 99%

Prenatal test cohort of a modified rat comparative thyroid assay adding brain thyroid hormone measurements and histology but lowering group size appears able to detect disruption by sodium phenobarbital

Minami,

Sato,

Tomiyama

et al. 2024

Current Research in Toxicology

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“…Group C comprised 45 animals that were divided into 3 subgroups. All these animals were given phenobarbitone by daily intraperitoneal injection of 100 mg/ kg for 2 months (Dingemanse et al, 1990). weight) (Christensen et al, 1970).…”

Section: Toxic Agentsmentioning

confidence: 99%

Ozone Administration Ameliorates Different Chemically Induced Hepato-Renal Chronic Toxicity in Rats : A Histopathological Study

Hassan¹,

El-Shawaf²,

El-Ghazaly³

et al. 2007

Mansoura Journal of Forensic Medicine and Clinical Toxicology

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The present work was an in vivo experimental study to investigate the toxic effects of different poisons on the histopathological picture of both the liver and kidney. Also the influence of repeated administration of ozone in atoxic doses on the progress of such toxicity was evaluated. The investigation was carried on 190 male albino rats (BW: 250-300 g). They were subdivided into four groups as follow: Group (A) composed of 65 animals. They received by oral intake of 1/20 LD50 of cadmium chloride (17.6 mg/kg BW). Group B comprised 65 animals which received 80 mg/kg BW. daily by oral administration of an organophosphorous (diazinon) (1/20LD50). Group C comprised 45 animals which received intraperitoneal injection of phenolbarbitone (100 mg/kg) daily. One third of animals in groups 1, 2 and 4 received the respective chemical only for 60 days. The second third received the same chemical for 60 days but during the last 10 days of the experiment, oxygen-ozone mixture as an adjuvant measure was taken while the remaining third received the toxic chemical for 60 days with addition of nitrogen intake in the last 10 days of the experiment. Group E (which acted as a normal control group) comprised 15 albino-rats which received the placebo substance (inert nitrogen) for two months. Marked histopathological changes in the liver and kidney of the experimental animals were noted due to cadmium chloride administration. Treatment of the cadmium intoxicated rats with oxygen-ozone mixture by daily intraperitoneal injection of 40 ul ozone in 1 ml oxygen during the last 10 days, showed marked improvement of the histopathological alterations in both liver and kidney. Moreover, marked histopathological alterations of liver and kidney of the motivated animals were noted after diazinon administration. Treatment of the animals with oxygen-ozone mixture by intraperitoneal injection during the last 10 days showed favorable quantitative and qualitative reduction of the pathological changes in both liver and kidney. In the 3rd group of the study, histopathological changes affecting both liver and kidney of the experimental animals were found after phenoborbitone administration. Treatment of rats exposed to overdose of phenobarbitone with oxygen-ozone mixture by intraperitoneal injection during the last 10 days resulted in moderate improvement of the histopathological alterations affecting liver and kidney. The 3 poisons used (cadmi

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Pharmacodynamics of Tolerance Development to the Anesthetic and Anticonvulsant Effects of Phenobarbital in Rats

Cited by 8 publications

References 26 publications

Recognition of Anesthetic Barbiturates by a Protein Binding Site: A High Resolution Structural Analysis

Recognition of Anesthetic Barbiturates by a Protein Binding Site: A High Resolution Structural Analysis

Prenatal test cohort of a modified rat comparative thyroid assay adding brain thyroid hormone measurements and histology but lowering group size appears able to detect disruption by sodium phenobarbital

Ozone Administration Ameliorates Different Chemically Induced Hepato-Renal Chronic Toxicity in Rats : A Histopathological Study

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