Delving into the Latest Updates on Gallopamil hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Gallopamil hydrochloride (JAN), D-600, DL-D-600

+ [3]

Target

Cav2.1

Mechanism

Cav2.1 inhibitors(calcium voltage-gated channel subunit alpha1 A inhibitors)

Therapeutic Areas

Nervous System DiseasesCardiovascular Diseases

Active Indication

Angina PectorisArrhythmias, CardiacHypertension

Inactive Indication-

Originator Organization-

Active Organization-

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date-

Regulation-

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Structure

Molecular FormulaC28H41ClN2O5

InChIKeyOKCRIUNHEQSXFD-UHFFFAOYSA-N

CAS Registry16662-46-7

Airway remodeling in asthma refers to numerous structural changes in the airway in asthmatic patients, with thickening of the airway smooth muscle layer as its core feature. However, the nature and sources of the abnormally increased airway smooth muscle cells (ASMCs) in airway remodeling remain unclear. ASMCs play a key role in the pathogenesis of fatal asthma; therefore, it is important to clarify the properties and sources of these ASMCs responsible for asthmatic airway remodeling, which may provide a new direction for the precise treatment for asthma.

Methods:

We performed a narrative review of the literature on PubMed, Web of Science, and Google Scholar databases searching for the cellular sources of ASMCs in asthmatic airway remodeling and their clinical relevance.

Key Content and Findings:

It has long been thought that ASMCs are the result of abnormal proliferation of the native ASMCs in asthma; however, increasing evidence suggests that increased "ASMCs" may be due to the differentiation/transdifferentiation of other cells including mesenchymal stem cells (MSCs), myofibroblasts (MYFs), pericytes, and epithelial-mesenchymal transition (EMT). Recently, several pharmacological and biological therapies aimed at "reducing asthmatic ASMCs" have been developed, among which gallopamil, JQ1 [an inhibitor of the bromodomain and extra-terminal domain (BET) protein family], and histone deacetylase (HDAC) inhibitors can alleviate asthma airway remodeling and hyperresponsiveness and improve asthma symptoms in both mouse models and preclinical experiments.

Conclusions:

As one of the core features of asthma, ASMCs are an important effector of airway remodeling. It has become extremely important to develop therapies for the reduction and prevention of the "ASMCs" on the basis of the properties and sources of "ASMCs". Many studies have shown that epigenetic regulation is closely related to the abnormal increase of ASMCs in asthma, and interfering with epigenetic regulation factors can reduce the increased smooth muscle cells. Although the epigenetic regulation of asthma is still in its nascent stage, epigenetic therapy targeting "ASMCs" may become another new strategy for asthma prevention and treatment.

01 Mar 2022·ChiralityQ4 · CHEMISTRY

Chiral separation of calcium channel antagonists by SFC and HPLC using different immobilized chiral stationary phases

Q4 · CHEMISTRY

Article

Author: Jain, Arvind K. ; Alam, Syed Dilshad ; Locatelli, Marcello ; Shirsath, Vikas ; Mukhopadhyay, Dipanjan ; Raja, Rupak ; Ali, Imran ; ALOthman, Zeid A.

Abstract:

Supercritical fluid chromatography and high‐performance liquid chromatography techniques are popular for the chiral separations of different drugs and pharmaceuticals. Therefore, this article describes a comparative study of the chiral separation of some calcium channel antagonists such as verapamil, gallopamil, and nisoldipine. The columns used were Chiralpak IG and Chiralpak ID (250 mm × 4.6 mm, 5.0 μm). The separation was achieved by using a variety of mobile phases in both techniques. The retention, separation, and resolution factors in SFC were in the range of 1.36–7.30, 1.09–1.72, and 1.16–3.47, while these values in the case of HPLC were 1.03–2.42, 1.12–1.35, and 0.49–2.46. The complete resolution of gallopamil and verapamil was achieved successfully. The chiral recognition was controlled by hydrogen bondings, π‐π interactions, dipole induced dipole interactions, van der Waal forces, and steric effects. SFC was found to be a better technique than HPLC because of quick separation, good separation power, economic, environment‐friendly, and green technology.

01 Aug 2021·The Journal of allergy and clinical immunologyQ1 · MEDICINE

Mitochondria are involved in bronchial smooth muscle remodeling in severe preschool wheezers

Q1 · MEDICINE

Article

Author: Celle, Alexis ; Esteves, Pauline ; Berger, Patrick ; Trian, Thomas ; Marthan, Roger ; Germande, Ophélie ; Enaud, Raphaël ; Fayon, Michael ; Beaufils, Fabien

BACKGROUND:

Bronchial remodeling is a key feature of asthma that is already present in preschoolers with wheezing. Moreover, bronchial smooth muscle (BSM) remodeling at preschool age is predictive of asthma at school age. However, the mechanism responsible for BSM remodeling in preschoolers with wheezing remains totally unknown. In contrast, in adult asthma, BSM remodeling has been associated with an increase in BSM cell proliferation related to increased mitochondrial mass and biogenesis triggered by an altered calcium homeostasis. Indeed, BSM cell proliferation was decreased in vitro by the calcium channel blocker gallopamil.

OBJECTIVE:

Our aim was to investigate the mechanisms involved in BSM cell proliferation in preschoolers with severe wheezing, with special attention to the role of mitochondria and calcium signaling.

METHODS:

Bronchial tissue samples obtained from 12 preschool controls without wheezing and 10 preschoolers with severe wheezing were used to measure BSM mass and establish primary BSM cell cultures. BSM cell proliferation was assessed by manual counting and flow cytometry, ATP content was assessed by bioluminescence, mitochondrial respiration was assessed by using either the Seahorse or Oroboros technique, mitochondrial mass and biogenesis were assessed by immunoblotting, and calcium response to carbachol was assessed by confocal microscopy. The effect of gallopamil was also evaluated.

RESULTS:

BSM mass, cell proliferation, ATP content, mitochondrial respiration, mass and biogenesis, and calcium response were all increased in preschoolers with severe wheezing compared with in the controls. Gallopamil significantly decreased BSM mitochondrial biogenesis and mass, as well as cell proliferation.

CONCLUSION:

Mitochondria are key players in BSM cell proliferation in preschoolers with severe wheezing and could represent a potential target to treat BSM remodeling at an early stage of the disease.

100 Deals associated with Gallopamil hydrochloride

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