Recent developments on oximes to improve the blood brain barrier penetration for the treatment of organophosphorus poisoning: a review

Norrrahim, Mohd Nor Faiz; Razak, Mas Amira Idayu Abdul; Shah, Noor Aisyah Ahmad; Kasim, Herdawati; Yusoff, Wan Yusmawati Wan; Halim, Norhana Abdul; Nor, Siti Aminah Mohd; Jamal, Siti Hasnawati; Ong, Keat Khim; Yunus, Wan Md Zin Wan; Knight, Victor Feizal; Kasim, Noor Azilah Mohd

doi:10.1039/c9ra08599h

Cited by 24 publications

(11 citation statements)

References 80 publications

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“…5 Unlike the OPs, oximes generally have a low degree of penetration through the BBB, because of which they have little to no ability to reactivate brain AChE. 7 Knowing that central respiratory depression is a main cause of death in OP intoxication, 8,9 when researching a new oxime, it is very important to determine the degree of its penetration through the BBB. Finding an oxime that is more penetrable, would mean a greater therapeutic success.…”

Section: The Marinković-maksimović Methods (Mm Method)mentioning

confidence: 99%

Preparing a rat brain tissue samples for acetylcholinesterase activity measurement: The MM method

Marinković¹,

Đukanović²,

Mandić-Kovačević³

et al. 2021

Scripta Medica

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Background/Aim: Organophosphorus compounds (OP) bind to acetylcholinesterase (AChE) causing an irreversible inhibition of the enzyme. When doing in vivo studies of OP intoxication, to precisely measure AChE activity in the brain tissue it is necessary to remove as much blood from the brain as possible. By doing so, interference of the OPs present in the blood is avoided. Usually this demands expensive equipment, therefore, the aim of this study was to find a simple and economical method to eliminate the blood from brain blood vessels. Methods: Wistar albino rats were divided into four groups named Control (C), Control washout (CW), Paraoxon (Pox) and Paraoxon washout (PoxW) group. Rats in Pox and PoxW were treated with 0.25 mg/kg paraoxon subcutaneously (sc), while C and CW received 1 mL/kg sc saline instead. The "Marinković-Maksimović" ("MM") method was performed in rats from PoxW and CW groups. Activity of AChE was measured both in erythrocyte lysate and in brain tissue using spectrophotometry. Results: Macroscopic examination revealed that the elimination of blood was achieved in CW and PoxW groups. Activity of AChE in homogenised brain tissue was expectedly lower in the Pox and PoxW group, when compared to C and CW group, respectively. The CW group had a lower value of AChE activity in the brain tissue compared to C group, while activity of AChE in the PoxW group was statistically higher than in the Pox group (p = 0.044). Conclusion: The MM method provides good elimination of blood from the brain. Together with blood, present confounding factors that interfere with analysis in homogenised brain tissue, were also eliminated.

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Section: The Marinković-maksimović Methods (Mm Method)mentioning

confidence: 99%

Preparing a rat brain tissue samples for acetylcholinesterase activity measurement: The MM method

Marinković¹,

Đukanović²,

Mandić-Kovačević³

et al. 2021

Scripta Medica

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“…However, none of them are yet to be manufactured. New oxime's structure, uncharged oximes, conjugation of uncharged oximes, and sugar-oxime moieties are among several strategies to increase the BBB penetration efficiency of oximes [61]. It has been reported that oximes get access into the brain and, thus, reactivate inhibited local AChE.…”

Section: Limitations Of Oximementioning

confidence: 99%

“…Another promising approach is to apply specific BBB transporters such as P-glycoprotein (Pgp) inhibitors and nanoparticles as drug carrier which has also been reported [120]. Due to the inadequate reports focused on the application of these approaches for oximes, the Pgp inhibitors and nanomaterial carriers for oxime delivery into the CNS need to be further studied in the future [61].…”

Section: Future Directions In the Treatment Of Op Poisoningmentioning

confidence: 99%

“…e development progress of the BBB-penetrating oxime is slow, and there are no reported novel compounds that are suitable for advanced development or into clinical use [36]. e searching and exploration of enhanced uncharged oximes with the ability to reactivate human AChE are still needed [60,61]. Recently, seven candidates of uncharged acetamido bis-oximes have been synthesized as reactivators [62].…”

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confidence: 99%

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Transitioning from Oxime to the Next Potential Organophosphorus Poisoning Therapy Using Enzymes

Mohamed

Ong

Kasim

et al. 2021

Journal of Chemistry

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For years, organophosphorus poisoning has been a major concern of health problems throughout the world. An estimated 200,000 acute pesticide poisoning deaths occur each year, many in developing countries. Apart from the agricultural pesticide poisoning, terrorists have used these organophosphorus compounds to attack civilian populations in some countries. Recent misuses of sarin in the Syrian conflict had been reported in 2018. Since the 1950s, the therapy to overcome this health problem is to utilize a reactivator to reactivate the inhibited acetylcholinesterase by these organophosphorus compounds. However, many questions remain unanswered regarding the efficacy and toxicity of this reactivator. Pralidoxime, MMB-4, TMB-4, obidoxime, and HI-6 are the examples of the established oximes, yet they are of insufficient effectiveness in some poisonings and only a limited spectrum of the different nerve agents and pesticides are being covered. Alternatively, an option in the treatment of organophosphorus poisoning that has been explored is through the use of enzyme therapy. Organophosphorus hydrolases are a group of enzymes that look promising for detoxifying organophosphorus compounds and have recently gained much interest. These enzymes have demonstrated remarkable protective and antidotal value against some different organophosphorus compounds in vivo in animal models. Apart from that, enzyme treatments have also been applied for decontamination purposes. In this review, the restrictions and obstacles in the therapeutic development of oximes, along with the new strategies to overcome the problems, are discussed. The emerging interest in enzyme treatment with its advantages and disadvantages is described as well.

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“…The large scale repeated use of nerve agents during the Iran-Iraq war in the 1980s against civilians by Iraqi troops, and during terrorist attacks by the Aum Shinrikyo sect in Japan [14], emphasize the constant threat and urgent Severe pain in exposed area, gastrointestinal distress, vomiting, cardiac arrhythmias need for the development of sensitive and specific diagnostic tools for CWA. In fact, simple synthesis and high toxicity [15] are the major reasons that have led to the significant use of these chemical materials during various wars, for example in Syria 2017, and for individual assassinations -February 2017 in Kuala Lumpur [16][17][18][19]. The rapid detection of these toxic agents in the environment, public places or workplaces and the monitoring of an individual's exposure to CWA become increasingly vital for homeland security and environment monitoring.…”

mentioning

confidence: 99%

Composites based on conductive polymer with carbon nanotubes in DMMP gas sensors – an overview

Nurazzi

Harussani

Zulaikha

et al. 2021

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A number of recent terrorist attacks make it clear that rapid response, high sensitivity and stability are essential in the development of chemical sensors for the detection of chemical warfare agents. Nerve agent sarin [2-(fluoro-methyl-phosphoryl) oxypropane] is an organophosphate (OP) compound that is recognized as one of the most toxic chemical warfare agents. Considering sarin’s high toxicity, being odorless and colorless, dimethyl methylphosphonate (DMMP) is widely used as its simulant in the laboratory because of its similar chemical structure and much lower toxicity. Thus, this review serves to introduce the development of a variety of fabricated chemical sensors as potential sensing materials for the detection of DMMP in recent years. Furthermore, the research and application of carbon anotubes in DMMP polymer sensors, their sensitivity and limitation are highlighted. For sorption-based sensors, active materials play crucial roles in improving the integral performances of sensors. The novel active materials providing hydrogen-bonds between the polymers and carbon nanotubes are the main focus in this review.

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Recent developments on oximes to improve the blood brain barrier penetration for the treatment of organophosphorus poisoning: a review

Abstract: Organophosphorus (OP) compounds are highly toxic synthetic compounds which have been used as pesticides and developed as warfare nerve agents.

Cited by 24 publications

References 80 publications

Preparing a rat brain tissue samples for acetylcholinesterase activity measurement: The MM method

Preparing a rat brain tissue samples for acetylcholinesterase activity measurement: The MM method

Transitioning from Oxime to the Next Potential Organophosphorus Poisoning Therapy Using Enzymes

Composites based on conductive polymer with carbon nanotubes in DMMP gas sensors – an overview

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