API-001(API-001) - 药物靶点：σ1 receptor_专利_临床

概要

基本信息

药物类型

小分子化药

别名

+ [3]

靶点

σ1 receptor

作用机制

σ1 receptor激动剂(σ-阿片受体激动剂)

治疗领域

感染神经系统疾病内分泌与代谢疾病+ [1]

在研适应症-

非在研适应症

新型冠状病毒感染糖尿病性神经病变疱疹后神经痛

原研机构

Esteve Pharmaceuticals S.A.

在研机构-

非在研机构

Esteve Pharmaceuticals S.A.

Consorci Mar Parc de Salut de Barcelona

最高研发阶段无进展临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C20H23N3O2

InChIKeyDGPGXHRHNRYVDH-UHFFFAOYSA-N

CAS号878141-96-9

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关联

7

项与 API-001 相关的临床试验

EUCTR2020-003603-33-ES / Unknown status临床2期IIT

Efficacy of E-52862 in the early treatment of confirmed mild symptomatic COVID-19 patients

开始日期2021-01-14

申办/合作机构

Consorci Mar Parc de Salut de Barcelona

EUCTR2012-000398-21-GR / Not yet recruitingN/A

A proof-of-concept phase 2, randomized, placebo-controlled, double blind, multicentre clinical trial in 2 parallel groups to evaluate the efficacy and safety of E-52862 for reducing the incidence and severity of oxaliplatin-induced peripheral neuropathy in patients treated for colorectal cancer.

开始日期2012-07-24

申办/合作机构

Esteve Pharmaceuticals S.A.

EUCTR2012-000399-41-ES / Not yet recruitingN/A

An exploratory, randomized, double blind, placebo controlled, parallel groups Phase II clinical trial to evaluate the efficacy and safety of E-52862 (400 mg) by oral route, in patients with postherpetic neuralgia (PHN).

开始日期2012-07-23

申办/合作机构-

100 项与 API-001 相关的临床结果

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100 项与 API-001 相关的转化医学

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100 项与 API-001 相关的专利（医药）

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42

项与 API-001 相关的文献（医药）

2024-07-01·Drug and Alcohol Dependence

Ethanol drinking at adulthood is sensitive to S1-R antagonism and is promoted by binge ethanol self-administration at adolescence

Article

作者: Morón, Ignacio ; Cendán, Cruz Miguel ; Marengo, Leonardo ; Salguero, Agustín ; Ruiz-Leyva, Leandro ; Pautassi, Ricardo Marcos

BACKGROUNDBinge drinking at adolescence is a risk factor for problematic alcohol (ethanol) consumption later in life, yet the murine studies that modelled this phenomenon via ethanol self-administration have provided mixed findings. Antagonism of the sigma-1 receptor (S1-R) system at adolescence modulates ethanol's motivational effects and intake. It is still unknown, however, whether this antagonism would protect against enhanced ethanol intake at adulthood after adolescent binge ethanol exposure.METHODSExp. 1 and 2 tested adults male or female Wistar rats -exposed or not to ethanol self-administration at adolescence (postnatal days 31-49; nine 2-hour sessions of access to 8-10% ethanol)- for ethanol intake using 24-h two-bottle choice test (Exp. 1) or time restricted, single-bottle, tests (Exp. 2). Experiments 2-5 evaluated, in adolescent or adult rats, the effects of the S1-R antagonist S1RA on ethanol intake and on ethanol-induced conditioned taste or place aversion. Ancillary tests (e.g., novel object recognition, ethanol-induced locomotor activity) were also conducted.RESULTSAdolescent ethanol exposure promoted ethanol consumption at both the restricted, single-bottle, and at the two-bottle choice tests conducted at adulthood. S1RA administration reduced ethanol intake at adulthood and facilitated the development of ethanol-induced taste (but not place) aversion.CONCLUSIONSS1RA holds promise for lessening ethanol intake after chronic and substantial ethanol exposure in adolescence that results in heightened ethanol exposure at adulthood. This putative protective effect of S1-R antagonism may relate to S1RA exacerbating the aversive effects of this drug.

2023-10-12·Biomedicines

Genetic and Pharmacological Blockade of Sigma-1 Receptors Attenuates Inflammation-Associated Hypersensitivity during Acute Colitis in CD1 Mice.

Article

作者: Carceller, Alicia ; López-Estévez, Sergio ; Aguilera, Mònica ; Gris, Georgia ; Martínez, Vicente ; de la Puente, Beatriz

Sigma-1 receptors (σ₁Rs) are implicated in nociception, including pain sensitization, and inflammation. We assessed the role of σ₁Rs on acute colitis-associated hypersensitivity using both genetic (constitutive knockout) and pharmacological blockade of the receptor. Colitis was induced in CD1 wild-type (WT) and σ₁R KO mice (exposure to dextran sodium sulfate, 3%). A von Frey test was used to assess referred mechanosensitivity (abdominal and plantar withdrawal responses). The effects of the selective σ₁R antagonists BD1063 and E-52862 were also assessed in WT animals. The expression of immune and sensory-related markers (RT-qPCR, Western blot) was assessed in the colon and lumbosacral spinal cord. The genetic ablation or pharmacological blockade of σ₁Rs attenuated acute colonic inflammation in a similar manner. Mechanosensitivity was similar in WT and σ₁R KO mice before colitis. In WT mice, but not in σ₁R KO, colitis was associated with the development of referred mechanical hypersensitivity, manifested as a reduction in the withdrawal thresholds to mechanical probing (paw and abdominal wall). In WT mice, BD1063 and E-52862 blocked colitis-associated hypersensitivity. A genotype- and treatment-related differential regulation of sensory-related markers was detected locally (colon) and within the spinal cord. σ₁Rs are involved in the development of acute intestinal inflammation and its associated referred mechanical hypersensitivity. The selective modulation of sensory-related pathways within the colon and spinal cord might be part of the underlying mechanisms. These observations support the pharmacological use of σ₁R antagonists for the treatment of intestinal inflammation-induced hypersensitivity.

2023-10-01·Pharmacological reports : PR

Novel object recognition test as an alternative approach to assessing the pharmacological profile of sigma-1 receptor ligands.

Article

作者: Bojarski, Andrzej J ; Szczepańska, Katarzyna ; Malikowska-Racia, Natalia ; Popik, Piotr

BACKGROUNDAlthough the terms "agonist" and "antagonist" have been used to classify sigma-1 receptor (σ₁R) ligands, an unambiguous definition of the functional activity is often hard. In order to determine the pharmacological profile of σ₁R ligands, the most common method is to assess their potency to alleviate opioid analgesia. It has been well established that σ₁R agonists reduce opioid analgesic activity, while σ₁R antagonists have been demonstrated to enhance opioid analgesia in different pain models.METHODSIn the present study, we evaluated the pharmacological profile of selected σ₁R ligands using a novel object recognition (NOR) test, to see if any differences in cognitive functions between σ₁R agonists and antagonists could be observed. We used the highly selective PRE-084 and S1RA as reference σ₁R agonist and antagonist, respectively. Furthermore, compound KSK100 selected from our ligand library was also included in this study. KSK100 was previously characterized as a dual-targeting histamine H₃/σ₁R antagonist with antinociceptive and antiallodynic activity in vivo. Donepezil (acetylcholinesterase inhibitor and σ₁R agonist) was used as a positive control drug.RESULTSBoth tested σ₁R agonists (donepezil and PRE-084) improved learning in the NOR test, which was not observed with the σ₁R antagonists S1RA and KSK100.CONCLUSIONSThe nonlinear dose-response effect of PRE-084 in this assay does not justify its use for routine assessment of the functional activity of σ₁R ligands.

100 项与 API-001 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
疱疹后神经痛	临床2期	西班牙	Esteve Pharmaceuticals S.A.	2012-07-17
糖尿病性神经病变	临床2期	西班牙	Esteve Pharmaceuticals S.A.	2012-06-13
新型冠状病毒感染	药物发现	西班牙	Consorci Mar Parc de Salut de Barcelona	2020-10-16