Delving into the Latest Updates on Meptazinol Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Meptazinol hydrochloride (USAN)

+ [4]

Target

Opioid receptors

Mechanism

Opioid receptors agonists(Opioid receptors agonists)

Therapeutic Areas

Nervous System Diseases

Active Indication

PainPain, PostoperativeModerate pain

Inactive Indication

Musculoskeletal Pain

Originator Organization-

Active Organization

Chengdu Medson Pharmaceutical Biotechnology Co., Ltd.Beijing Dezhong Wanquan Medicine Technology Co., Ltd.

Inactive Organization

Yang Zi Jiang Yao Ye Si Chuan Hai Rong Yao Ye You Xian Gong SiShandong Taitian New Drug Development Co., Ltd.

Drug Highest PhaseApproved

First Approval Date-

Regulation-

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Structure

Molecular FormulaC15H24ClNO

InChIKeyMPJUSISYVXABBH-UHFFFAOYSA-N

CAS Registry59263-76-2

View All Structures (2)

The pathogenesis of Alzheimer’s disease (AD) involves multiple pathophysiological processes. Oxidative stress is a major cause of AD-associated neuronal injury. The current research was designed to examine whether a novel (-)-meptazinol-serotonin hybrid (Mep-S) with potent antioxidant activity and additional inhibitory properties for acetylcholinesterase (AChE) activity could attenuate oxidative neuronal damage and cognitive deficits. In human SH-SY5Y cells, Mep-S suppressed H2O2-induced apoptosis by restoring mitochondrial membrane potential and inhibiting caspase-3 activation. Meanwhile, it attenuated oxidative stress elicited by H2O2 through lessening generation of reactive oxygen species as well as enhancing production of glutathione (GSH) and activity of superoxide dismutase (SOD). Mechanistically, Mep-S promoted nuclear translocation of a transcription factor nuclear factor E2-related factor-2 (Nrf2) in H2O2-challenged cells. This effect was accompanied by reduction in Kelch-like ECH-associated protein-1 (Keap1) levels as well as augmentation of Akt phosphorylation and expression of heme oxygenase-1 (HO-1) and NAD(P)H quinine oxidoreductase-1 (NQO-1). Molecular docking analysis revealed that Mep-S may disrupt the protein-protein interactions between Keap1 and Nrf2. In an in vivo mouse model, Mep-S attenuated scopolamine-caused cognitive deficits with inhibition of apoptotic neuronal death and brain AChE activity. Furthermore, the scopolamine-induced impairment of total antioxidant capacity and reduction in SOD1, SOD2, and γ-glutamate-cysteine ligase expression in the brain were counteracted by Mep-S, accompanied by decreased Keap1 levels, increased Akt catalytic subunit and Nrf2 phosphorylation, and decreased Nrf2, HO-1, and NQO-1 expression. Collectively, our results suggest that Mep-S ameliorates apoptotic neuronal death and memory dysfunction associated with oxidative stress by regulating the Nrf2/antioxidant enzyme pathway through inactivating Keap1 and phosphorylating Nrf2 via Akt activation. Therefore, Mep-S may be a potential lead for multitarget neuroprotective agents to treat AD-like symptoms.

06 May 2022·The Journal of Organic ChemistryQ2 · CHEMISTRY

Asymmetric Total Synthesis of Meptazinol

Q2 · CHEMISTRY

Article

Author: Reiser, Oliver ; Babl, Tobias

The first enantioselective synthesis of (S)-meptazinol in 14 steps from commercially available ethyl 4-oxo-3,4-dihydropyridine-1(2H)-carboxylate, being widely used in racemic form for pain treatment, and, en route, the formal synthesis of two anti-Alzheimer's agents are reported. A novel ring expansion of 2-azabicyclo[4.1.0]heptanes, readily available via the stereoselective cyclopropanation of 1,2,3,4-tetrahydropyridine-4-ols, provides an effective entry to 3,3-disubstituted azepanes that represent the core for a variety of approved drugs.

01 Dec 2021·Zeitschrift für Geburtshilfe und NeonatologieQ4 · MEDICINE

Auswirkungen geburtshilflicher Analgesie mit systemischen Opioiden auf das Neugeborene – eine Übersichtsarbeit

Q4 · MEDICINE

Review

Author: Ebenebe, Chinedu Ulrich ; Seiler, Berenike ; Deindl, Philipp ; Hecher, Kurt ; Somville, Thierry ; Singer, Dominique

100 Deals associated with Meptazinol Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
D04924	Meptazinol Hydrochloride	N02AX05	DB13478

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Pain	-	-	-

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Pain, Postoperative	Phase 3	CN	Chengdu Medson Pharmaceutical Biotechnology Co., Ltd.	08 May 2015
Moderate pain	Discovery	CN	Yang Zi Jiang Yao Ye Si Chuan Hai Rong Yao Ye You Xian Gong Si	05 Mar 2013
Musculoskeletal Pain	Discovery	CN	Yang Zi Jiang Yao Ye Si Chuan Hai Rong Yao Ye You Xian Gong Si	05 Mar 2013