Delving into the Latest Updates on Pipecuronium Bromide with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Pipecurium, Pipecuronium, Pipecuronium bromide (JAN/USAN/INN)

+ [4]

Target

nAChRα1/β1/δ/γ

Mechanism

AChR antagonists(Acetylcholine receptor; alpha1/beta1/delta/gamma antagonists), 肌松剂(Muscle relaxation agents)

Therapeutic Areas

Other Diseases

Active Indication-

Inactive Indication

Anesthesia

Originator Organization

Merck & Co., Inc.

Active Organization-

Inactive Organization

Organon USA, Inc.

Drug Highest PhaseWithdrawn

First Approval Date

US (26 Jun 1990),

Anesthesia

Regulation-

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Structure

Molecular FormulaC35H62BrN4O4

InChIKeyFMUOAYRSFAPXFH-MHLFSCIFSA-M

CAS Registry52212-02-9

Hepatitis C virus (HCV) infection causes viral hepatitis leading to hepatocellular carcinoma. Despite the clinical use of direct-acting antivirals (DAAs) still there is treatment failure in 5-10% cases. Therefore, it is crucial to develop new antivirals against HCV. In this endeavor, we developed the "Anti-HCV" platform using machine learning and quantitative structure-activity relationship (QSAR) approaches to predict repurposed drugs targeting HCV non-structural (NS) proteins. We retrieved experimentally validated small molecules from the ChEMBL database with bioactivity (IC₅₀/EC₅₀) against HCV NS3 (454), NS3/4A (495), NS5A (494) and NS5B (1671) proteins. These unique compounds were divided into training/testing and independent validation datasets. Relevant molecular descriptors and fingerprints were selected using a recursive feature elimination algorithm. Different machine learning techniques viz. support vector machine, k-nearest neighbour, artificial neural network, and random forest were used to develop the predictive models. We achieved Pearson's correlation coefficients from 0.80 to 0.92 during 10-fold cross validation and similar performance on independent datasets using the best developed models. The robustness and reliability of developed predictive models were also supported by applicability domain, chemical diversity and decoy datasets analyses. The "Anti-HCV" predictive models were used to identify potential repurposing drugs. Representative candidates were further validated by molecular docking which displayed high binding affinities. Hence, this study identified promising repurposed drugs viz. naftifine, butalbital (NS3), vinorelbine, epicriptine (NS3/4A), pipecuronium, trimethaphan (NS5A), olodaterol and vemurafenib (NS5B) etc. targeting HCV NS proteins. These potential repurposed drugs may prove useful in antiviral drug development against HCV.

01 Dec 2021·BMC anesthesiologyQ4 · MEDICINE

Carboxymethyl-γ-cyclodextrin, a novel selective relaxant binding agent for the reversal of neuromuscular block induced by aminosteroid neuromuscular blockers: an ex vivo laboratory study

Q4 · MEDICINE

ArticleOA

Author: Fábián, Ákos I ; Fülesdi, Béla ; Tassonyi, Edömér ; Csernoch, Vera ; Szente, Lajos ; Fedor, Marianna ; Sohajda, Tamás

Abstract:

Background:

Residual neuromuscular block at the end of surgery may compromise the patient’s safety. The risk of airway complications can be minimized through monitoring of neuromuscular function and reversal of neuromuscular block if needed. Effective reversal can be achieved with selective relaxant binding agents, however, sugammadex is the only clinically approved drug in this group.We investigated the concentration–response properties of a novel selective relaxant binding agent, carboxymethyl-γ-cyclodextrin for the reversal of neuromuscular block. We evaluated the hypothesis that it is equally potent for reversing neuromuscular block as sugammadex.

Methods:

Phrenic nerve – hemidiaphragm tissue preparations were isolated from male Wistar rats and suspended in a tissue holder allowing electrical stimulation of the nerve and monitoring of muscle contraction force. Concentration–response relationships were constructed for the neuromuscular blocking agents rocuronium, pipecuronium, and vecuronium. The half-effective concentrations of sugammadex and carboxymethyl-γ-cyclodextrin for reversal of neuromuscular block were determined.

Results:

The half effective concentrations (95% confidence interval, CI) were 7.50 (6.93–8.12) μM for rocuronium, 1.38 (1.33–1.42) μM for pipecuronium, and 3.69 (3.59–3.80) μM for vecuronium. The half effective concentrations (95% CI) of carboxymethyl-γ-cyclodextrin and sugammadex were 35.89 (32.67–39.41) μM and 3.67 (3.43–3.92) μM, respectively, for the reversal of rocuronium-induced block; 10.14 (9.61–10.70) μM and 0.67 (0.62–0.74) μM, respectively, for the reversal of pipecuronium-induced block; and 376.1 (341.9–413.8) μM and 1.45 (1.35–1.56) μM, respectively, for the reversal of vecuronium-induced block.

Conclusions:

Carboxymethyl-γ-cyclodextrin is an effective, but less potent agent for reversal of neuromuscular block than sugammadex.

01 Jan 2020·Kardiochirurgia i torakochirurgia polska = Polish journal of cardio-thoracic surgery

The use of multimodal low-opioid anesthesia for coronary artery bypass grafting surgery in conditions of artificial blood circulation

Article

Author: Druzina, Oleksandr ; Dzuba, Dmitryi ; Danchyna, Taisiia ; Loskutov, Oleg

INTRODUCTION:

Cardiovascular diseases (CVD) are the main cause of death worldwide, and according to experts, they will continue to dominate the structure of global mortality.

AIM:

The effectiveness of the multimodal low-opioid anesthesia technique in performing coronary artery bypass graft operations with artificial blood circulation.

MATERIAL AND METHODS:

Ninety-six patients aged 61.8 ±10.4 years underwent coronary artery bypass grafting under artificial blood circulation. Group I: propofol, sevoflurane, fentanyl, pipecuronium bromide (standard doses). Group II: dexketoprofen trometamol (50 mg), intravenous lidocaine (1% - 1 mg/kg bolus) and continuous lidocaine infusion (1.5-2 mg/kg/h), propofol, ketamine (0.5 mg/kg), magnesia sulfate, minimal doses of fentanyl.

RESULTS:

Average duration of anesthesia - 257.4 ±19.1 min; assisted blood circulation - 55 ±10 min. Mean dose of fentanyl in group I - 4.66 ±1.58 µg/kg/h, in group II - 1.29 ±0.32 µg/kg/h.Standard lab values and stress hormonal changes were within the normal range (mean cortisol: 479.3 ±26.4 nmol/l, lactate 1.61 ±0.2 mmol/l, glucose 6.42 ±0.9 mmol/l). Changes in heart rate within group I had a significant amplitude of dynamics, while in group II, these values were relatively at the same level throughout the entire anesthetic provision. Mean arterial pressure changes in group I were characterized by a significant reduction at the stage of induction, support and sternum reduction, whereas in group II it was relatively at the same level during the entire anesthetic management and significantly differed from baseline only at the stage of induction.

CONCLUSIONS:

Multimodal low-opioid anesthesia during coronary artery bypass surgery with artificial blood circulation allows one to ensure adequate analgesia and avoid the intraoperative usage of routine doses of fentanyl, as indicated by the absence of hemodynamic and endocrine-metabolic changes.

100 Deals associated with Pipecuronium Bromide

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