Delving into the Latest Updates on Pralidoxime Chloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

2-PAM-chloride, Pralidoxime (INN), Pralidoxime chloride (USP)

+ [3]

Target

AChE

Mechanism

AChE activators(Acetylcholinesterase activators)

Therapeutic Areas

NeoplasmsImmune System DiseasesNervous System Diseases+ [3]

Active Indication

Muscle WeaknessMyasthenia GravisOrganophosphate Poisoning+ [1]

Inactive Indication-

Originator Organization

Baxter International, Inc.

Active Organization

BAXTER HEALTHCARE CORP ANESTHESIA AND CRITICAL CARE

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

US (11 Mar 1964),

Muscle WeaknessMyasthenia GravisOrganophosphate Poisoning+ [1]

Regulation-

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Structure

Molecular FormulaC7H9ClN2O

InChIKeyHIGSLXSBYYMVKI-UHFFFAOYSA-N

CAS Registry51-15-0

This open level randomized controlled trial will be conducted in the department of medicine at Sir Salimullah Medical College and Mitford Hospital. Clinical severity will be assessed by the POP (Peradeniya Organophosphorus Poisoning) scale of admitted patients having a history of organophosphorus poisoning within 24 hours with clinical features and physical evidence of poisoning consumed. Only moderate severity (POP Scale score 4-7) of OPC (Organophosphorus compound) patients will be included in this study. Then one group of patients will be treated with atropine and pralidoxime and another group will be treated with atropine. The outcome will be noted as clinical improvement or recovery. hospital stay, requirement of ICU, death.

Start Date01 Jun 2022

Sponsor / Collaborator-

IRCT20170609034406N5 / RecruitingPhase 3IIT

Study of the efficacy of pralidoxime in the treatment of organophosphorus poisoning

Start Date30 Jun 2020

Sponsor / Collaborator

Tabriz University of Medical Sciences

IRCT20180613040087N1 / RecruitingPhase 3IIT

Comparison of continuous infusion versus intermittent bolus injection of Pralidoxime for the treatment of Organophosphate poisoning

Start Date23 Jul 2018

Sponsor / Collaborator

Shiraz University of Medical Sciences

100 Clinical Results associated with Pralidoxime Chloride

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100 Translational Medicine associated with Pralidoxime Chloride

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100 Patents (Medical) associated with Pralidoxime Chloride

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1,169

Literatures (Medical) associated with Pralidoxime Chloride

01 Dec 2024·Journal of Toxicology and Environmental Health, Part A

Drosophila melanogaster as a model organism for screening acetylcholinesterase reactivators

Article

Author: Franco, Jeferson Luis ; Posser, Thais ; Macedo, Pablo Echeverria ; Farina, Marcelo ; Kuca, Kamil ; Pinto, Paulo Marcos ; Boldo, Juliano Tomazzoni ; Souza, Lorena Raspanti ; Dafre, Alcir Luiz ; Batista, Jéssica Eduarda Santos

The widely used insecticide chlorpyrifos (CP) is known to inhibit acetylcholinesterase (AChE) activity attributed to result in various neurological disorders and acetylcholine-dependent organ functions including heart, skeletal muscle, lung, gastrointestinal tract, and central nervous systems. Enzyme reactivators, such as oximes, are known to restore AChE activity and mitigate adverse effects. The identification of compounds that reactivate AChE constitute agents with important therapeutic beneficial effects in cases of pesticide poisoning. However, the screening of novel drugs using traditional models may raise ethical concerns. This study aimed to investigate the potential of Drosophila melanogaster as a model organism for screening AChE reactivators, with a focus on organophosphate poisoning. The efficacy of several oximes, including pralidoxime, trimedoxime, obidoxime, methoxime, HI-6, K027, and K048, against CP-induced AChE activity inhibition in D. melanogaster was determined in silico, in vitro, and in vivo experiments. Molecular docking studies indicated a strong interaction between studied oximes and the active-site gorge of AChE. Data showed that selected oximes (100 μM) are effective in the reactivation of AChE inhibited by CP (10 μM) in vitro. Finally, in vivo investigations demonstrated that selected oximes, pralidoxime and K048 (1.5 ppm), reversed the locomotor deficits, inhibition of AChE activity as well as lowered the mortality rates induced by CP (0.75 ppm). Our findings contribute to utilization of D. melanogaster as a robust model for determination of actions of identified new AChE inhibitory agents with more effective therapeutic properties that those currently in use in the clinical practice in treatment of AChE associated disorders.

01 Dec 2024·Bioorganic Chemistry

Simplified scalable synthesis of a water-soluble toll-like receptor 2 agonistic lipopeptide adjuvant for use with protein-based viral vaccines

Article

Author: Petrovsky, Nikolai ; Salunke, Deepak B ; Brar, Deshkanwar S ; Patil, Madhuri T. ; Salunke, Deepak B. ; Patil, Madhuri T ; Honda-Okubo, Yoshikazu ; Kaur, Arshpreet ; Brar, Deshkanwar S.

Toll-like receptors (TLRs) form a key bridge between the innate and adaptive immune systems. The lipopeptide based TLR2 agonists such as Pam₂CSK₄ are promising vaccine adjuvants but drawbacks include its surfactant like nature and cumbersome synthesis. Although the TLR2 activity of Pam₂CS-OMe is commensurate with Pam₂CSK₄, its water solubility is much less, rendering it ineffective for clinical use. In the present investigation, we designed a synthesis pathway for a novel water-soluble TLR2-active analogue, Pam₂CS-DMAPA (13), which enhanced the immunogenicity of recombinant SARS-CoV2 and hepatitis B antigens in mice. Co-formulation of compound 13 with 2 % aluminium hydroxide gel led to a further significant improvement in vaccine immunogenicity. This synthetically simpler compound 13 was water soluble and equally potent to Pam₂CSK₄ adjuvant, but was superior in terms of manufacturing simplicity and scalability. This makes compound 13 a promising TLR2 targeted adjuvant for further development.

01 Oct 2024·Neurotoxicity Research

Pharmacology of Adenosine A1 Receptor Agonist in a Humanized Esterase Mouse Seizure Model Following Soman Intoxication

Article

Author: Munoz, Crystal ; Acon-Chen, Cindy ; Keith, Zora-Maya ; Shih, Tsung-Ming

AbstractRecently a novel genetically modified mouse strain with serum carboxylesterase knocked-out and the human acetylcholinesterase gene knocked-in (KIKO) was created to simulate human responses to nerve agent (NA) exposure and its standard medical treatment. A1 adenosine receptor (A1AR) agonist N-bicyclo-(2.2.1)-hept-2-yl-5'-chloro-5'-deoxyadenosine (ENBA) alone is a potent anticonvulsant and neuroprotectant (A/N) in both rat and KIKO mouse soman (GD) seizure models. In this study we utilized the KIKO mouse to evaluate further the basic pharmacologic A/N effects of ENBA as an adjunct to standard NA medical treatments (i.e., atropine sulfate, pralidoxime chloride [2-PAM], and midazolam). Male mice, implanted with cortical electroencephalographic (EEG) electrodes, were pretreated with asoxime (HI-6) and exposed to an epileptogenic dose of GD (33 µg/kg, s.c.) or saline (sham exposure) and then treated 15 min after seizure onset with ENBA at 15 mg/kg, i.p. (a minimum efficacy dose in suppressing NA-induced seizure) alone or as an adjunct to standard medical treatments. We collected EEG activity, seizure suppression outcomes, daily body temperature and weight, heart rate, toxic signs, neuropathology, and lethality data for up to 14 days. Without ENBA, death from NA exposure was 45%, while with ENBA, either alone or in combination with midazolam, the survival improved to 80% and 90%, respectively. Additionally, seizure was suppressed quickly and permanently, toxic signs, hypothermia, and bradycardia recovered by 48 h, and no neuropathology was evident. Our findings confirmed that ENBA is a potent A/N adjunct for delayed medical treatments of NA exposure.

1

News (Medical) associated with Pralidoxime Chloride

05 Sep 2023

·www.fiercepharma.com

Government-backed autoinjector specialist AktiVax shutters 'substantially all of its operations,' lays off 70

Jobs that will be affected at AktiVax run the gamut from patent prosecution and purchasing agents to engineers, technicians, quality control microbiologists and human resources executives. Despite scoring a number of federal contracts in recent years, it’s lights out for government-backed rescue autoinjector maker AktiVax. Late last month, AktiVax, also known as Aktiv Pharma Group, informed the state of Colorado that “the company must shut down substantially all of its operations,” citing “unexpected circumstances.” In turn, the company is mothballing three manufacturing facilities and laying off around 70 employees. The plant closures and layoffs are set to affect a facility in Broomfield, Colorado, plus two sites in Fort Collins, according to a letter sent to a state official. The “entire plants” are to be closed, and AktiVax expects the action will be “permanent.” Jobs that will be affected run the gamut from patent prosecution and purchasing agents to engineers, technicians, quality control microbiologists and human resources executives. AktiVax’s business primarily revolves around its autoinjector ARAI, which the company says is the only autoinjector with single-hand, single-step activation. AktiVax has won several federal contracts in recent years, with the Denver Business Journal noting the company has publicly announced more than $275 million in government pacts since 2018. Back in the spring of 2020, for instance, AktiVax was awarded $24.5 million for a U.S. government project to develop an autoinjector treatment for exposure to nerve agents. The five-year pact put AktiVax on deck to develop and win approval for a scopolamine hydrobromide autoinjector for several nerve agents. In a press release at the time, the company noted emergency nerve agent treatment was well suited to autoinjectors given the speediness and ease of use of the delivery format. Meanwhile, in 2018, the Biomedical Advanced Research and Development Authority granted AktiVax $15.5 million to develop a manufacturing-approved production line for the ARAI autoinjector. The company notes it completed that project in Dececember 2019. AktiVax’s most recent contract appears to be from October 2022, the month the company won a $45 million contract to supply pralidoxime chloride autoinjectors for the Strategic National Stockpile. That deal, also focused on nerve agent antidotes, was set to reach a value of upward of $220 million over seven years. At the time, the company said it was also working with another unnamed drugmaker to develop a reconstitution autoinjector for a long-acting formulation of the popular opioid overdose reversal agent naloxone.

100 Deals associated with Pralidoxime Chloride

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External Link

KEGG	Wiki	ATC	Drug Bank
D00469	Pralidoxime Chloride	V03AB04	DBSALT000242

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Muscle Weakness	US	BAXTER HEALTHCARE CORP ANESTHESIA AND CRITICAL CARE	11 Mar 1964
Myasthenia Gravis	US	BAXTER HEALTHCARE CORP ANESTHESIA AND CRITICAL CARE	11 Mar 1964
Organophosphate Poisoning	US	BAXTER HEALTHCARE CORP ANESTHESIA AND CRITICAL CARE	11 Mar 1964
Respiratory Insufficiency	US	BAXTER HEALTHCARE CORP ANESTHESIA AND CRITICAL CARE	11 Mar 1964

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


Pubmed \| PLoS Med	Not Applicable	Organophosphate Poisoning	-	Pralidoxime chloride	(natasbiyjt) = qzzudiliem lkxewwvqqw (fmluzqcrji ) View more	Negative	30 Jun 2009
				Saline placebo	(natasbiyjt) = oxlabjmrvc lkxewwvqqw (fmluzqcrji ) View more
NCT00333944 (Pubmed \| Lancet)	Not Applicable	Organophosphate Poisoning	200	Constant pralidoxime infusion	(ccuizxhfao) = cerljglrlw edhniipvtr (ybacaebskp )	Positive	16 Dec 2006
				Repeated bolus injection	(ccuizxhfao) = jldwbyclzm edhniipvtr (ybacaebskp )