Comparative physiology and efficacy of atropine and scopolamine in sarin nerve agent poisoning

Cornelissen, Alex S.; Klaassen, Steven D.; Groningen, Tomas van; Bohnert, Sara; Joosen, Marloes J.A.

doi:10.1016/j.taap.2020.114994

Cited by 14 publications

(7 citation statements)

References 46 publications

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“…In contrast, the elimination in the present study was much slower than what Angelis et al described. Of note, BZ shows a similar plasma profile as atropine (maximal concentration 363.3 ± 42.0 ng/ml at 7.8 ± 2.1 min), and the brain concentrations correspond to those of atropine as well 26 . Compared to scopolamine, however, the plasma concentration of BZ rose slowly (maximal concentration 604.9 ± 161.0 ng/ml at 3.4 ± 2.1 min) and the brain concentrations were lesser than in scopolamine 26 …”

Section: Discussionmentioning

confidence: 70%

3‐Quinuclidinyl benzilate (agent BZ) toxicokinetics in rats

Dlabková

Herman

Cechova

et al. 2021

Basic Clin Pharma Tox

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3‐Quinuclidinyl benzilate (BZ) ranks among incapacitating military warfare agents. It acts as a competitive inhibitor on muscarinic receptors leading to non‐lethal mental impairment. The present study aimed to investigate toxicokinetics of BZ in rats. Moreover, BZ can be exploited to produce a pharmacological model of Alzheimer's disease; thus, this paper focuses mainly on the BZ distribution to the brain. Wistar rats were administered i.p. with BZ (2 and 10 mg/kg). The BZ concentration was determined using LC‐MS/MS in plasma, urine, bile, brain, kidney and liver. The sample preparation was based on a solid phase extraction (liquids) or protein precipitation (organ homogenates). The plasma concentration peaked at 3 min (204.5 ± 55.4 and 2185.5 ± 465.4 ng/ml). The maximal concentration in the brain was reached several minutes later. Plasma elimination half‐life was 67.9 ± 3.4 in the 2 mg/kg group and 96.6 ± 27.9 in the 10 mg/kg group. BZ concentrations remained steady in the brain, with slow elimination (t1/2 506.9 ± 359.5 min). Agent BZ is excreted mainly via the urine. Steady BZ concentration in the brain could explain the previously published duration of the significant impairment in passive avoidance tasks in rats after an injection of BZ.

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Section: Discussionmentioning

confidence: 70%

3‐Quinuclidinyl benzilate (agent BZ) toxicokinetics in rats

Dlabková

Herman

Cechova

et al. 2021

Basic Clin Pharma Tox

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“…Cornelissen et al, in 2020, declared that Scopolamine and Atropine manifested similar bioavailability in their study, but Atropine provided lower CNS levels. This effect is associated with an improved anticonvulsant effect of Scopolamine ( Cornelissen et al, 2020 ). Scopolamine should be given initially at 2–0.6 mg IM or IV.…”

Section: Methodsmentioning

confidence: 99%

A complete, evidence-based review on novichok poisoning based on epidemiological aspects and clinical management

et al. 2023

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Background: The whole world has learned about the existence of a highly toxic neuro-paralytic substance called Novichok. A wide range of neuro-paralytic toxins were used during the wars of decades ago, which also had harmful and irreversible effects. Fortunately, the establishment of conventions prohibiting the use of these weapons prevented the adverse clinical consequences of these compounds. What we did in the present study was to evaluate the clinical features of Novichok, how to manage exposure to it, and to evaluate the prognostic aspects associated with this poisoning agent.Methods: The manuscript especial databases including Medline, Web of knowledge, Google scholar, and Scopus were deeply searched by the two blinded investigators for all eligible studies based on the considered keywords. Initially 98 articles were initially collected by database searching that considering eligibility criteria, 83 articles were finally eligible for the final assessment. There is a lack of clinical trials and case-cohort studies on general population about treatment and side effects when it comes to human nerve agents and most of the data in our search is based on animal studies.Results: In evaluating various clinical, auto physiological and prognostic aspects of exposure to these substances, special attention was necessary to the following points. First, Novichok agents are considered more potent than other toxic agents. Pathophysiologically, these agents irreversibly bind acetylcholinesterase and produce a rapid cholinergic toxidrome which is responsible for the clinical manifestations as well as the potential dangerous and life threatening side effects caused by these agents. Uniquely, these agents are thought to also target every neuron in the central and peripheral nervous system. As a managerial and therapeutic approach, early and timely treatment of its related complication along with prevents massive exposure and decontamination in addition to rapid resuscitation can prohibit debilitating neuropathy and death due to facing it.Conclusion: The present review highlights the importance of recognizing the potential acute toxic effects of Novichok agents, diagnostic and therapeutic approaches (life-saving antidotal therapy) to complications and ultimately the application of guidelines to improve the prognosis of exposure to these agents for both victims and medical community.

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“…One possibility is that the poisonous or even lethal properties of some of these drugs is related to their boosting of catecholaminergic signaling, especially norepinephrine and epinephrine. Atropine and scopolamine are two alkaloid drugs found in certain nightshade plants, that are muscarinic cholinergic receptor antagonists [ 15 ]. Figure 4 A describes a proposed series of reactions in which atropine is converted to dopamine in the body.…”

Section: Proposed Pathways and Published Data Related To The Hypothesismentioning

confidence: 99%

Many Drugs of Abuse May Be Acutely Transformed to Dopamine, Norepinephrine and Epinephrine In Vivo

Fitzgerald

2021

IJMS

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It is well established that a wide range of drugs of abuse acutely boost the signaling of the sympathetic nervous system and the hypothalamic–pituitary–adrenal (HPA) axis, where norepinephrine and epinephrine are major output molecules. This stimulatory effect is accompanied by such symptoms as elevated heart rate and blood pressure, more rapid breathing, increased body temperature and sweating, and pupillary dilation, as well as the intoxicating or euphoric subjective properties of the drug. While many drugs of abuse are thought to achieve their intoxicating effects by modulating the monoaminergic neurotransmitter systems (i.e., serotonin, norepinephrine, dopamine) by binding to these receptors or otherwise affecting their synaptic signaling, this paper puts forth the hypothesis that many of these drugs are actually acutely converted to catecholamines (dopamine, norepinephrine, epinephrine) in vivo, in addition to transformation to their known metabolites. In this manner, a range of stimulants, opioids, and psychedelics (as well as alcohol) may partially achieve their intoxicating properties, as well as side effects, due to this putative transformation to catecholamines. If this hypothesis is correct, it would alter our understanding of the basic biosynthetic pathways for generating these important signaling molecules, while also modifying our view of the neural substrates underlying substance abuse and dependence, including psychological stress-induced relapse. Importantly, there is a direct way to test the overarching hypothesis: administer (either centrally or peripherally) stable isotope versions of these drugs to model organisms such as rodents (or even to humans) and then use liquid chromatography-mass spectrometry to determine if the labeled drug is converted to labeled catecholamines in brain, blood plasma, or urine samples.

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Comparative physiology and efficacy of atropine and scopolamine in sarin nerve agent poisoning

Cited by 14 publications

References 46 publications

3‐Quinuclidinyl benzilate (agent BZ) toxicokinetics in rats

3‐Quinuclidinyl benzilate (agent BZ) toxicokinetics in rats

A complete, evidence-based review on novichok poisoning based on epidemiological aspects and clinical management

Many Drugs of Abuse May Be Acutely Transformed to Dopamine, Norepinephrine and Epinephrine In Vivo

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