更新于：2024-11-21

A2B agonist(National Institutes of Health)

更新于：2024-11-21

概要

研发状态

概要

基本信息

药物类型

小分子化药

别名

2-(3' '-(6' '-Bromoindolyl)ethyloxy)adenosine、Compound 28(National Institutes of Health)

靶点

A1R x A2aR x A2bR x A3R

作用机制

A1R激动剂(腺苷A1受体激动剂)、A2aR激动剂(腺苷A2a受体激动剂)、A2bR激动剂(腺苷A2b受体激动剂)

+ [1]

治疗领域-

在研适应症-

非在研适应症-

原研机构

National Institutes of Health

在研机构

National Institutes of Health

非在研机构-

最高研发阶段药物发现

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C20H21BrN6O5

InChIKeyOXLUZSPXALFOBX-NVQRDWNXSA-N

CAS号936252-34-5

关联

100 项与 A2B agonist(National Institutes of Health) 相关的临床结果

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100 项与 A2B agonist(National Institutes of Health) 相关的转化医学

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100 项与 A2B agonist(National Institutes of Health) 相关的专利（医药）

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项与 A2B agonist(National Institutes of Health) 相关的文献（医药）

2014-12-01·Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

Osteoblast differentiation and survival: A role for A2B adenosine receptor allosteric modulators

Article

作者: Daniele, Simona ; Da Settimo, Federico ; Martini, Claudia ; Taliani, Sabrina ; Trincavelli, Maria Letizia ; Cosimelli, Barbara ; Novellino, Ettore ; Greco, Giovanni ; Giacomelli, Chiara

The A2B adenosine receptor (A2B AR), activated in response to high levels of endogenous adenosine, is the major AR subtype involved in mesenchymal stem cell (MSC) differentiation to osteoblasts and bone formation. For this reason, targeting of A2B AR with selective allosteric modulators may represent a promising pharmacological approach to the treatment of bone diseases. Herein, we report the characterization of a 3-keto-indole derivative, 2-(1-benzyl-1H-indol-3-yl)-2-oxo-N-phenylacetamide (KI-7), as A2B AR positive allosteric modulator in MSCs, demonstrating that this compound is able to potentiate the effects of either adenosine and synthetic orthosteric A2B AR agonists in mediating osteoblast differentiation in vitro. In detail, we observed that MSC treatment with KI-7 determined an increase in the expression of osteoblast-related genes (Runx2 and osterix) and osteoblast marker proteins (phosphatase alkaline and osteocalcin), associated with a stimulation of osteoblast mineralization. In the early phase of differentiation programme, KI-7 significantly potentiated physiological and A2B AR agonist-mediated down-regulation of IL-6 release. Conversely, during the late stage of differentiation, when most of the cells have an osteoblast phenotype, KI-7 caused a sustained raise in IL-6 levels and an improvement in osteoblast viability. These data suggest that a positive allosteric modulation of A2B AR not only favours MSC commitment to osteoblasts, but also ensures a greater survival of mature osteoblasts. Our study paves the way for a therapeutic use of selective positive allosteric modulators of A2B AR in the control of osteoblast differentiation, bone formation and fracture repair.

2013-08-01·Journal of Anesthesia

Is dexmedetomidine or remifentanil alone an optimal sedation scheme for awake intubation?

Letter

作者: Jia Qiang Zhang ; Fu Shan Xue ; Fan Min Meng

To the Editor: In a double-blind randomized controlled clinical trial comparing dexmedetomidine and remifentanil sedation for awake fiberoptic nasotracheal intubation, Hu et al. [1] showed that both drugs were effective. Moreover, compared with remifentanil, dexmedetomidine produced better endoscopy scores, lower incidence of recall, greater patient satisfaction, and fewer hemodynamic effects. They should be applauded for their efforts to provide useful evidence regarding dexmedetomidine and remifentanil sedation for awake airway management. However, in preparing the patient for awake intubation, the optimal sedation regimen would provide comfort and sedation as well as prevention from negative recall of the procedure. Furthermore, it should ensure good airway reflex suppression under sufficient spontaneous ventilation, hemodynamic stability, and adequate intubating conditions [2]. Based on the findings of this study, we are not sure that some of above targets have been well achieved. First, coughing during awake intubation occurred in 50 % of patients in the dexmedetomidine group and 15 % of patients in the remifentanil group, respectively. It is generally believed that during awake intubation, coughing is frequently reported as one of the most distressing symptoms and described as an undesirable feature [3]. Second, 30–40 % of patients in the dexmedetomidine group and 65–70 % of patients in the remifentanil group had recall for airway procedure events. Such high incidences of recall would put patients at a risk of postoperative psychological morbidity, such as anxiety, depression, posttraumatic stress disorder, cognitive impairment, etc. A main limitation of this study design is the use of a single agent to provide sedation. Actually, none of the drugs currently in use can meet all criteria of the optimal sedation regimen for awake intubation, although many of them have some of the desirable characteristics. For example, opioids can provide analgesia and help blunt airway reflexes, but use of opioids alone fails to provide amnesia [4]. Benzodiazepines have no analgesic effect, but are useful for providing good amnesia, even if the procedure itself appears to be painful. Thus, it is generally recommended that an optimal sedation regimen for awake intubation requires the use of a combination of sedatives, analgesics, and antipsychotic agents [4]. For example, midazolam and propofol, are common agents used for sedation, often with an opioid drug such as fentanyl or remifentanil. It must be pointed out that in a review of four studies, including 443 cases of awake intubation, even if various combinations of sedatives and analgesics are utilized, 17 % of patients still have partial recall and 6 % have recall with unpleasant memories [4]. Dexmedetomidine is a highly selective a2-agonist with anxiolysis and some analgesia without respiratory depression. An answer to this letter to the editor is available at doi:10.1007/s00540-013-1561-4.

2013-01-01·Anesthesia: Essays and Researches

Comparison between dexmedetomidine and midazolam premedication in pediatric patients undergoing ophthalmic day-care surgeries

Article

作者: Puri, Garima ; Louis, Thaju ; Bhuva, Mayur ; Bhadla, Shailesh ; Prajapati, Deepal ; Panchal, Saurin

Midazolam is the most commonly used premedication in children. It has been shown to be more effective than parental presence or placebo in reducing anxiety and improving compliance at induction of anesthesia. Clonidine, an a2 agonist, has been suggested as an alternative. Dexmedetomidine is a more a2 selective drug with more favorable pharmacokinetic properties than clonidine.AIMSTo compare i.v. Dexmedetomidine and Midazolam as premedication in pediatric patients.SETTINGS AND DESIGNOpen label single blind study.MATERIAL AND METHODS60 patients were randomly allocated to group D(n=30) and group M(n=30) and given Inj Dexmedetomidine 0.4 μg/kg diluted in 10 ml slowly i.v. and Inj Midazolam 0.05mg/kg i.v. accordingly. Level of sedation, parent separation, response to induction, blood pressure, pulse, oxygen saturation, post operative agitation and shivering was noted.STATISTICAL ANALYSIS USEDUnpaired student's t-test and chi square test used in this study. P value <0.05 was considered significant.RESULTSThere were significant differences in parental separation acceptance,Response to induction and wake-up behavior score. When compared with group M, patients in groupD were significantly more sedated % minutes after premedication (P<0.001). Post operative agitation and shivering was low in group D in comparision with group M. Though blood pressure and pulse were on lower side in group D than in group M, oxyden saturation remained same in both the groups having no statistical significance.CONCLUSIONSDexmedetomidine is superior than Midazolam as premedication in pediatric patients with more intense sedation, excellent parent separation, favourable induction conditions, lower incidence of postoperative agitation and shivering along with hemodynamic stability and no respiratory depression.

100 项与 A2B agonist(National Institutes of Health) 相关的药物交易

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