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Last update 23 Jan 2025

α2C-AR

Last update 23 Jan 2025

Basic Info

Synonyms

ADRA2C, ADRA2L2, ADRA2RL2

+ [8]

Introduction

Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.

Drugs associated with α2C-AR

Clonixin

Target

α2A-AR x α2B-AR x α2C-AR

Mechanism

ADRA2B agonists [+2]

Active Org.-

Originator Org.-

Active Indication

Pain

Inactive Indication-

Drug Highest PhaseApproved

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

DB-105

Target

α2C-AR

Mechanism

α2C-AR antagonists

Active Org.

Denovo Biopharma LLC [+3]

Originator Org.

Orion Oyj

Active Indication

Alzheimer Disease [+2]

Inactive Indication

Aggression [+3]

Drug Highest PhasePhase 2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

BAY-2925976

Target

α2C-AR

Mechanism

α2C-AR antagonists

Active Org.

Bayer AG

Originator Org.

Bayer AG

Active Indication

Sleep Apnea, Obstructive

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with α2C-AR

NCT03440021

/ CompletedPhase 1

The Effects of Single-dose Administration of a Novel Selective alpha2c Antagonist on Emotional and Cognitive Processing in Healthy Volunteers: an fMRI Investigation

The aim of the present study is to investigate changes in neural activity (BOLD signal), as measured using fMRI, in brain areas associated with emotional and working memory during task performance after single-dose administration of a novel selective alpha2c adrenoceptor antagonist (ORM-12741) in healthy volunteers. Further, it will be explored whether ORM-12741 affects connectivity between brain areas in rest, as measured using fMRI, and cognitive performance in the sample under investigation.

Start Date26 Mar 2018

Sponsor / Collaborator

University of Cape Town

[+2]

NCT03128320

/ CompletedPhase 2

A Randomized, Single-blind, Threefold Crossover, Single-center Study to Assess the Safety and the Effects of 1 mg and 5 mg BAY1193397 in Comparison to Placebo on Skin Capillary Blood Flow and Transcutaneous Oxygen Pressure After Single Dose in Type II Diabetic Patients

The purpose of the study is to analyse skin blood flow in diabetic patients. The patients receive a single dose of placebo, 1 mg BAY1193397, and 5 mg BAY1193397. The analysis of safety and tolerability are secondary objectives of this study.

Start Date25 May 2017

Sponsor / Collaborator

Bayer AG

EUCTR2014-000217-30-BG

/ Not yet recruitingPhase 2

EFFICACY OF ORM-12741 ON AGITATION/AGGRESSION SYMPTOMS IN PATIENTSWITH ALZHEIMER’S DISEASE: A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED,PARALLEL GROUP, MULTICENTRE STUDY OF 12 WEEKS - NEBULA

Start Date15 Oct 2015

Sponsor / Collaborator

Orion Oyj

100 Clinical Results associated with α2C-AR

100 Translational Medicine associated with α2C-AR

0 Patents (Medical) associated with α2C-AR

426

Literatures (Medical) associated with α2C-AR

01 Jan 2025·Progress in Cardiovascular Diseases

Cigarette smoke extract induces p38-mediated expression and ROS/rho-mediated translocation of alpha 2C adrenoceptor in human microvascular smooth muscle cells

Article

Author: Khachab, Maha ; Dakroub, Ali ; Matar, Aya ; Eid, Ali H ; Fardoun, Manal M

Raynaud's phenomenon (RP) is a vascular disease characterized by exaggerated vasoconstriction in response to stressors, mainly cold and emotional stress. This vasoconstriction is mediated solely by alpha 2C-adrenoceptors (α_2C-AR) expressed in vascular smooth muscle cells of dermal arterioles. Several factors, among which is cigarette smoking, are associated with aggravated symptoms of and increased risk for RP. Evidence shows that cigarette smoking induces the production of reactive oxygen species (ROS), which is a major driver of RP pathogenesis. However, the exact mechanism by which smoking contributes to RP or α_2C-AR remains unclear. Here, we show that cigarette smoke extract (CSE) upregulates the expression of α_2C-AR in a concentration- and time-dependent manner in VSMCs extracted from human dermal arterioles. This increase is associated with the activation of p38 MAPK, as pretreatment with SB-202190, a p38 specific inhibitor, attenuated CSE-induced α_2C-AR expression. Furthermore, our results show that CSE induces ROS production followed by increased RhoA activation. We also show that CSE induces translocation of vascular α_2C-AR to the plasma membrane, and that this mobilization is attenuated by inhibiting ROS via N-acetylcysteine or apocynin. Similarly, inhibition of Rho kinase via H- 11522 abolished CSE-induced α_2C-AR translocation. Collectively, these results indicate that CSE activates two different signaling pathways to induce the expression and the translocation of α_2C-AR. While CSE activates a p38-dependent mechanism to increase α_2C-AR expression, it initiates the receptor's spatial and functional rescue via a ROS/RhoA signaling pathway. These results provide mechanistic insight into the effect of cigarette smoking on RP, and further reinforce that smoking avoidance/cessation is critical to manage this disease, especially in the absence of a definitive drug for RP.

01 Oct 2024·Clinical Pharmacology & Therapeutics

Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 Genotypes and Beta‐Blocker Therapy

Review

Author: Stein, C. Michael ; Huddart, Rachel ; Lee, Craig R. ; van Schaik, Ron H. N. ; Klein, Teri E. ; Schwab, Matthias ; Uppugunduri, Chakradhara Rao S. ; Agundez, Jose A. G. ; Nagy, Mohamed ; Thomas, Cameron D. ; Caudle, Kelly E. ; Donnelly, Roseann S. ; Baye, Jordan F. ; Lanfear, David E. ; Duarte, Julio D. ; Monte, Andrew A. ; Luzum, Jasmine A. ; Gaedigk, Andrea

Beta‐blockers are widely used medications for a variety of indications, including heart failure, myocardial infarction, cardiac arrhythmias, and hypertension. Genetic variability in pharmacokinetic (e.g., CYP2D6) and pharmacodynamic (e.g., ADRB1, ADRB2, ADRA2C, GRK4, GRK5) genes have been studied in relation to beta‐blocker exposure and response. We searched and summarized the strength of the evidence linking beta‐blocker exposure and response with the six genes listed above. The level of evidence was high for associations between CYP2D6 genetic variation and both metoprolol exposure and heart rate response. Evidence indicates that CYP2D6 poor metabolizers experience clinically significant greater exposure and lower heart rate in response to metoprolol compared with those who are not poor metabolizers. Therefore, we provide therapeutic recommendations regarding genetically predicted CYP2D6 metabolizer status and metoprolol therapy. However, there was insufficient evidence to make therapeutic recommendations for CYP2D6 and other beta‐blockers or for any beta‐blocker and the other five genes evaluated (updates at www.cpicpgx.org).

22 Jan 2024·Journal of Biomolecular Structure and Dynamics

Tracing the pathways and mechanisms involved in the anti-breast cancer activity of glycyrrhizin using bioinformatics tools and computational methods

Article

Author: Hashemipour, Hassan ; Poustforoosh, Alireza ; Faramarz, Sanaz ; Tüzün, Burak ; Negahdaripour, Manica

A complete investigation to understand the pathways that could be affected by glycyrrhizin (licorice), as anti-breast cancer (BC) agent, has not been performed to date. This study aims to investigate the pathways involved in the anti-cancer activity of glycyrrhizin against BC. For this purpose, the target genes of glycyrrhizin were obtained from the ChEMBL database. The BC-associated genes for three types of BC (breast carcinoma, malignant neoplasm of breast, and triple-negative breast neoplasms) were retrieved from DisGeNET. The target genes of glycyrrhizin and the BC-associated genes were compared, and the genes with disease specificity index (DSI) > 0.6 were selected for further evaluation using in silico methods. The protein-protein interaction (PPI) network was constructed, and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed. The potential complexes were further evaluated using molecular dynamics (MD) simulation. The results revealed that among 80 common genes, ten genes had DSI greater than 0.6, which included POLK, TACR2, MC3R, TBXAS1, HH1R, SLCO4A1, NPY2R, ADRA2C, ADRA1A, and SLCO2B1. The binding affinity of glycyrrhizin to the cognate proteins and binding characteristics were assessed using molecular docking and binding free energy calculations (MM/GBSA). POLK, TBXAS1, and ADRA1A showed the highest binding affinity with -8.9, -9.3, and -9.6 kcal/mol, respectively. The final targets had an association with BC at several stages of tumor growth. By affecting these targets, glycyrrhizin could influence and control BC efficiently. MD simulation suggested the pathways triggered by the complex glycyrrhizin-ADRA1A were more likely to happen.Communicated by Ramaswamy H. Sarma.

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α2C-AR

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