Last update 01 Nov 2024

α1A-AR x α2A-AR

Last update 01 Nov 2024

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

414

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

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·Shock

α2-ADRENORECEPTOR ANTAGONIST AMELIORATES SEPSIS-ASSOCIATED PULMONARY FIBROSIS BY SUPPRESSING NOREPINEPHRINE-MEDIATED FIBROBLAST DIFFERENTIATION VIA INHIBITING PKC ACTIVATION

Article

Author: Wang, Yiyang ; Lin, Wan ; Chen, Yihua ; Wang, Miao ; Lu, Fan ; Su, Xingyu ; Wang, Huadong ; Yin, Haiyan ; Tang, Guoqing ; Liu, Yingwen

ABSTRACTPulmonary fibrosis is an important factor affecting the prognosis of severe septic patients with acute lung injury. The objective of this study was to explore the effect of norepinephrine (NE) and α2-adrenoreceptor (AR) on sepsis-associated pulmonary fibrosis and the mechanism underlying these effects. We found pulmonary fibrotic changes, and increased NE production and α2A-AR expression in the pulmonary tissue of mice subjected to cecal ligation and puncture surgery. Reserpine and yohimbine alleviated pulmonary fibrosis in mice with sepsis by exhausting NE derived from the lung's adrenergic nerve and blocking α2-AR, respectively. There was no significant difference in the expression of the three α1-AR subtypes. The effect of NE on promoting pulmonary fibroblast differentiation in vitro was suppressed by yohimbine. Both the protein and mRNA expression levels of α2A-AR were increased in pulmonary fibroblasts treated with LPS. Clonidine, a selective α2-AR agonist, enhanced LPS-induced differentiation in pulmonary fibroblasts, as indicated by the increase in α-smooth muscle actin and collagen I/III, which was mitigated by inhibiting PKC and p38. Further in vivo results indicated that yohimbine alleviated pulmonary fibrosis and inhibited the phosphorylation of PKC, p38, and Smad2/3 in lung tissue of mice exposed to LPS for 4 weeks. Clonidine showed the opposite effect to yohimbine, which aggravated LPS-induced pulmonary fibrosis. These findings demonstrated that the sepsis-induced increase in NE promoted fibroblast differentiation via activating α2-AR. Blockage of α2-AR effectively ameliorated sepsis-associated pulmonary fibrosis by abolishing NE-induced lung fibroblast differentiation and inhibiting the PKC-p38-Smad2/3 pathway.

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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