Experimental Diazepam Intoxication in Rodents: Physostigmine and Naloxone as Potential Antagonists

Walz, Marjorie A.; Davis, William S.

doi:10.3109/01480547908998247

Cited by 8 publications

(3 citation statements)

References 11 publications

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“…However, naloxone could prevent some diazepam effects in animal studies. [16][17][18][19][20][21] This study is one of the scant studies about naloxone effects on benzodiazepines poisoning. This study shows that clinical symptoms of such poisoning (including lethargy, weekness, ataxia and so on) improve with naloxone to a great extent in comparison with control group and the level of consciousness reaches the normal level more rapidly.…”

Section: Discussionmentioning

confidence: 99%

Benefit effect of naloxone in benzodiazepines intoxication: Findings of a preliminary study

et al. 2010

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Background: Naloxone, as a low-priced and available drug, may be useful in improvement of signs and symptoms of benzodiazepines intoxication. The aim of this study was assessment of its effect on benzodiazepines poisoning. Methods: In this clinical-trial study, patients with typical signs and symptoms of benzodiazepines poisoning, who were referred to a poisoning center in Tehran in 2008, were selected. After recording of patients’ characteristics, supportive treatment was initiated and patients were randomly assigned to the case group with intravenous (IV) injection of two 0.4 mg naloxone ampules or to the control group. Their signs and symptoms were evaluated again 0.5 hour later. Each of diazepam, clonazepam and alperazolam drug group had 30 patients and lorazepam drug group had 26 patients, half of which patients in each drug group received naloxone. Results: Most of the participants were female and the mean age was 28 years. There were no significant differences between case and control groups in age, sex, time of drug consumption, tablet counts, signs and symptoms and level of consciousness at the admission time in each drug types. After naloxone injection in case groups, all signs and symptoms significantly improved in all drug types in comparison to control groups except nystagmus. In addition, level of consciousness significantly improved in case groups in all drug types except lorazepam. Conclusion: Findings of the study showed that naloxone is effective in management of benzodiazepines poisoning. However, future clinical trials with greater sample size are recommened.

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Section: Discussionmentioning

confidence: 99%

Benefit effect of naloxone in benzodiazepines intoxication: Findings of a preliminary study

et al. 2010

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“…However, significant tolerability issues are associated with doses of this magnitude, limiting translation to a clinically relevant dosing paradigm. A single 20 mg/kg IP dose can cause complete loss of righting reflex for >80 min 8 . Hence, a dosing regimen that maintains therapeutic DZP concentrations in the brain without producing substantial behavioral impairment is needed.…”

Section: Introductionmentioning

confidence: 99%

“…A single 20 mg/kg IP dose can cause complete loss of righting reflex for >80 min. 8 Hence, a dosing regimen that maintains therapeutic DZP concentrations in the brain without producing substantial behavioral impairment is needed.…”

Section: Introductionmentioning

confidence: 99%

Development of a novel dosing paradigm to model diazepam rescue therapy in preclinical seizure and epilepsy models

Guignet,

White,

Misra

et al. 2024

Epilepsia Open

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Diazepam is a cornerstone immediate‐use antiseizure rescue therapy that may extend the duration between seizure clusters in people living with epilepsy. However, our mechanistic understanding of intermittent rescue therapy on disease progression is limited by the lack of suitable preclinical models. Specifically, the pharmacokinetics of diazepam varies widely between humans and laboratory animals. Here, we developed a novel repeat rescue therapy dosing paradigm in rats to maintain prolonged therapeutic concentrations seen in humans. Rats received three diazepam doses separated by 1 h (0.75, 1.5, or 3 mg/kg, intraperitoneal); plasma and brains were collected at 10 min and 1, 3, or 6 h following the last dose. Plasma and brain concentrations followed a dose‐dependent increase with peak concentrations following the repeat 3 mg/kg paradigm (180 ng/mL) being equivalent to plasma levels observed in human studies with diazepam nasal spray. Increased brain‐to‐plasma ratios in this paradigm indicate that diazepam accumulation in the brain may be long‐acting at the site of action. Overall, our repeat diazepam dosing paradigm mimics drug concentrations and accumulation seen in humans, offering a preclinical tool to study the impact of benzodiazepine rescue therapy on seizure‐cluster biology in rodent models of epilepsy.Plain language summaryThere is more to learn about how diazepam works in the brains of people who use it only when they have two or more seizures in 24 h (this is called a seizure cluster). Ethical studies in animals can be used to learn more about medicines in the body. In this study, we showed that three doses of diazepam in rats give about the same amount of the drug as one dose for a person. We can now test rats with epilepsy to see how the drug might work in people who take it when needed for seizure clusters.

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Stimulus-sensitive myoclonus of the baboon Papio papio: Pharmacological studies reveal interactions between benzodiazepines and the central cholinergic system

Rektor

Bryère

Silva-Barrat

et al. 1986

Experimental Neurology

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Experimental Diazepam Intoxication in Rodents: Physostigmine and Naloxone as Potential Antagonists

Cited by 8 publications

References 11 publications

Benefit effect of naloxone in benzodiazepines intoxication: Findings of a preliminary study

Benefit effect of naloxone in benzodiazepines intoxication: Findings of a preliminary study

Development of a novel dosing paradigm to model diazepam rescue therapy in preclinical seizure and epilepsy models

Stimulus-sensitive myoclonus of the baboon Papio papio: Pharmacological studies reveal interactions between benzodiazepines and the central cholinergic system

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