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Last update 23 Jan 2025

α1A-AR x α2A-AR

Last update 23 Jan 2025

Basic Info

Related Targets

α1A-ARα2A-AR

Drugs associated with α1A-AR x α2A-AR

BDF 6143

Target

α1A-AR x α2A-AR

Mechanism

α1A-AR modulators [+1]

Active Org.-

Originator Org.-

Active Indication-

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Cirazoline

Target

α1A-AR x α2A-AR

Mechanism

α1A-AR agonists [+1]

Active Org.-

Originator Org.

Sanofi

Active Indication-

Inactive Indication

Hypotension

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Xylometazoline Hydrochloride/Sodium Cromoglicate

Target

ADRA1 x ADRA2 x α1A-AR x α2A-AR x α2B-AR

Mechanism

ADRA1 agonists [+3]

Active Org.-

Originator Org.

Fisons Plc

Active Indication-

Inactive Indication

Rhinitis, Allergic

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with α1A-AR x α2A-AR

CTR20131777

/ CompletedPhase 2

色甘赛洛鼻喷雾剂治疗过敏性鼻炎多中心、随机双盲双模拟、阳性药平行对照临床研究

[Translation] A multicenter, randomized, double-blind, double-dummy, positive-drug parallel-controlled clinical study of crogancel nasal spray in the treatment of allergic rhinitis

评价色甘赛洛鼻喷雾剂治疗过敏性鼻炎的安全性和有效性。

[Translation]

To evaluate the safety and efficacy of cromoglucose nasal spray in the treatment of allergic rhinitis.

Start Date28 Mar 2008

Sponsor / Collaborator

Beijing Hua Xi Lianhe Tech & Development Ltd.

100 Clinical Results associated with α1A-AR x α2A-AR

100 Translational Medicine associated with α1A-AR x α2A-AR

0 Patents (Medical) associated with α1A-AR x α2A-AR

420

Literatures (Medical) associated with α1A-AR x α2A-AR

01 Feb 2025·Chemico-Biological Interactions

Modulatory roles of capsaicin on thermogenesis in C2C12 myoblasts and the skeletal muscle of mice

Article

Author: Yun, Jong Won ; Lee, Young Rok ; Lee, Jae Young ; Abdillah, Alfin Mohammad

Capsaicin, a polyphenol, is known to regulate energy expenditure and thermogenesis in adipocytes and muscles. However, its role in modulating uncoupling proteins (UCPs) and adenosine triphosphate (ATP)-dependent thermogenesis in muscles remains unclear. This study investigated the mechanisms underlying the role of capsaicin in modulating the UCP- and ATP-dependent thermogenesis in C2C12 myoblasts, as well as the gastrocnemius (GM) and soleus muscles (SM) of mice. We employed molecular dynamics (MD), quantitative real-time polymerase chain reactions (qRT-PCR), immunoblots, staining methods, and assay kits to investigate the role of capsaicin on thermogenesis and its modulatory roles on the transient receptor potential cation channel subfamily V member 1 (TRPV1) and α-/β-adrenergic receptors (ARs) using in vitro and in vivo models. Our findings demonstrate that capsaicin treatment in high-fat diet-induced obese mice reduces weight gain and elevates the expression of UCP- and ATP-dependent thermogenic effectors through ATP-consuming calcium and creatine futile cycles. In vitro and in vivo models capsaicin treatment elevated the expression of sarcoendoplasmic/endoplasmic reticulum calcium ATPases (SERCA-1 and -2), ryanodine receptors (RYR-1 and -2), uncoupling proteins (UCP-2 and -3), creatine kinase B (CKB), and creatine kinase mitochondrial 2 (CKMT2), through activation of TRPV1, α1-, β2-, and β3-AR as well as the suppressed expression of α2-AR. Furthermore, our results also indicate that capsaicin promotes myotube development and enhances lipid metabolism in C2C12 cells. We found that capsaicin increased intracellular Ca²⁺ levels and the expression of the voltage-dependent anion channel (VDAC) and mitochondrial calcium uniporter (MCU), suggesting that elevated mitochondrial Ca²⁺ levels boost the expression of oxidative phosphorylation protein complexes via the activation of the ATP-futile cycle. Mechanistic studies in C2C12 cells revealed that TRPV1 is likely dispensable for capsaicin-induced thermogenesis, and TRPV1 and α1-AR may synergistically induce thermogenesis. Collectively, our findings have uncovered a novel mechanism of UCP- and ATP-dependent thermogenesis and its associated pathways in both cellular and animal models which is crucial for designing therapeutic strategies to address obesity and associated metabolic diseases.

27 Jun 2024·Journal of Medicinal Chemistry

Structure-Based Drug Design of ADRA2A Antagonists Derived from Yohimbine

Article

Author: Česnek, Michal ; Kužmová, Erika ; Dvořáková, Alexandra ; Dračínský, Martin ; Brož, Břetislav ; Chayka, Artem ; Kozák, Jaroslav ; Strmeň, Timotej ; Janeba, Zlatko ; Mertlíková-Kaiserová, Helena ; Osifová, Zuzana ; Tloušt'ová, Eva

Yohimbine, a natural indole alkaloid and a nonselective adrenoceptor antagonist, possesses potential benefits in treating inflammatory disorders and sepsis. Nevertheless, its broader clinical use faces challenges due to its low receptor selectivity. A structure-activity relationship study of novel yohimbine analogues identified amino esters of yohimbic acid as potent and selective ADRA2A antagonists. Specifically, amino ester 4n, in comparison to yohimbine, showed a 6-fold higher ADRA1A/ADRA2A selectivity index (SI > 556 for 4n) and a 25-fold higher ADRA2B/ADRA2A selectivity index. Compound 4n also demonstrated high plasma and microsomal stability, moderate-to-low membrane permeability determining its limited ability to cross the blood-brain barrier, and negligible toxicity on nontumor normal human dermal fibroblasts. Compound 4n represents an important complementary pharmacological tool to study the involvement of adrenoceptor subtypes in pathophysiologic conditions such as inflammation and sepsis and a novel candidate for further preclinical development to treat ADRA2A-mediated pathologies.

01 Dec 2023·Neuroscience Bulletin

Peripheral BDNF Regulates Somatosensory–Sympathetic Coupling in Brachial Plexus Avulsion-Induced Neuropathic Pain

Article

Author: Zhang, Jian-Lei ; Guo, Huan ; Xian, Hang ; Liu, Yuan-Ying ; Yu, Ming-Jun ; Cong, Rui ; Xie, Rou-Gang ; Zhao, Rui ; Hu, Wen-Chao ; Zhang, Hang

Brachial plexus avulsion (BPA) is a combined injury involving the central and peripheral nervous systems. Patients with BPA often experience severe neuropathic pain (NP) in the affected limb. NP is insensitive to the existing treatments, which makes it a challenge to researchers and clinicians. Accumulated evidence shows that a BPA-induced pain state is often accompanied by sympathetic nervous dysfunction, which suggests that the excitation state of the sympathetic nervous system is correlated with the existence of NP. However, the mechanism of how somatosensory neural crosstalk with the sympathetic nerve at the peripheral level remains unclear. In this study, through using a novel BPA C7 root avulsion mouse model, we found that the expression of BDNF and its receptor TrκB in the DRGs of the BPA mice increased, and the markers of sympathetic nervous system activity including α1 and α2 adrenergic receptors (α1-AR and α2-AR) also increased after BPA. The phenomenon of superexcitation of the sympathetic nervous system, including hypothermia and edema of the affected extremity, was also observed in BPA mice by using CatWalk gait analysis, an infrared thermometer, and an edema evaluation. Genetic knockdown of BDNF in DRGs not only reversed the mechanical allodynia but also alleviated the hypothermia and edema of the affected extremity in BPA mice. Further, intraperitoneal injection of adrenergic receptor inhibitors decreased neuronal excitability in patch clamp recording and reversed the mechanical allodynia of BPA mice. In another branch experiment, we also found the elevated expression of BDNF, TrκB, TH, α1-AR, and α2-AR in DRG tissues from BPA patients compared with normal human DRGs through western blot and immunohistochemistry. Our results revealed that peripheral BDNF is a key molecule in the regulation of somatosensory-sympathetic coupling in BPA-induced NP. This study also opens a novel analgesic target (BDNF) in the treatment of this pain with fewer complications, which has great potential for clinical transformation.

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