Pozanicline Hydrochloride(Pozanicline Hydrochloride) - 药物靶点：CHRNA7 x nAChR α4/β2/α5 x nAChRα3&β4_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Pozanicline、Pozanicline Tartrate

+ [2]

靶点

CHRNA7 x nAChR α4/β2/α5 x nAChRα3&β4

作用机制

nAChR α4/β2/α5激动剂(烟碱性胆碱能受体α4/β2/α5复合体激动剂)、α3β4 receptor拮抗剂(神经性乙酰胆碱受体蛋白α3/β4复合体拮抗剂)、α7 receptor激动剂(神经性乙酰胆碱受体蛋白α-7亚基激动剂)

治疗领域

神经系统疾病其他疾病

在研适应症-

非在研适应症

阿尔茨海默症注意缺陷障碍伴多动

原研机构

AbbVie, Inc.

在研机构-

非在研机构

Abbott Laboratories

AbbVie, Inc.

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C11H16N2O

InChIKeyYRVIKLBSVVNSHF-JTQLQIEISA-N

CAS号161417-03-4

查看全部结构式(2)

关联

11

项与 Pozanicline Hydrochloride 相关的临床试验

NCT01756053 / Terminated临床2期IIT

A Pilot Feasibility Study of the Effects of ABT-089 on Smoking Abstinence Symptoms and Reward

This Phase IIa within-subject, cross-over pilot study will evaluate the effects of ABT-089 (an experimental medication not approved by the FDA) when administered as 40mg oral once daily dose for 10 days, compared to placebo, on the following: abstinence-induced cognitive deficits, smoking withdrawal, smoking urges, smoking reward, and a brief, monitored quit attempt (
4 days). The key cognitive domains include: working memory, sustained attention, and response inhibition.

开始日期2013-03-01

申办/合作机构

University of Pennsylvania

NCT00809510 / Terminated临床2期

A Study of the Long-term Safety of ABT-089 for Subjects With Mild-to-moderate Alzheimer's Disease Who Participated in the M06-876 Study

The purpose of this study is to evaluate the long-term safety and tolerability of ABT-089 in adults with mild-to-moderate Alzheimer's disease.

开始日期2009-01-01

申办/合作机构

Abbott Laboratories

NCT00686933 / Completed临床2期

The Long-Term Safety and Tolerability of ABT-089 in Adults With Attention Deficit-Hyperactivity Disorder (ADHD): An Open-Label Extension Study for Subjects Completing Study M10-346

The objective of this study is to evaluate the long-term effects and tolerability of ABT-089 in adults with Attention-Deficit/Hyperactivity Disorder (ADHD).

开始日期2008-05-01

申办/合作机构

AbbVie, Inc.

100 项与 Pozanicline Hydrochloride 相关的临床结果

登录后查看更多信息

100 项与 Pozanicline Hydrochloride 相关的转化医学

登录后查看更多信息

100 项与 Pozanicline Hydrochloride 相关的专利（医药）

登录后查看更多信息

31

项与 Pozanicline Hydrochloride 相关的文献（医药）

2020-04-01·Psychopharmacology3区 · 医学

Dissociation of nicotinic α7 and α4/β2 sub-receptor agonists for enhancing learning and attentional filtering in nonhuman primates

3区 · 医学

Article

作者: Azimi, Marzyeh ; Womelsdorf, Thilo ; Oemisch, Mariann

RATIONALENicotinic acetylcholine receptors (nAChRs) modulate attention, memory, and higher executive functioning, but it is unclear how nACh sub-receptors mediate different mechanisms supporting these functions.OBJECTIVESWe investigated whether selective agonists for the alpha-7 nAChR versus the alpha-4/beta-2 nAChR have unique functional contributions for value learning and attentional filtering of distractors in the nonhuman primate.METHODSTwo adult rhesus macaque monkeys performed reversal learning following systemic administration of either the alpha-7 nAChR agonist PHA-543613 or the alpha-4/beta-2 nAChR agonist ABT-089 or a vehicle control. Behavioral analysis quantified performance accuracy, speed of processing, reversal learning speed, the control of distractor interference, perseveration tendencies, and motivation.RESULTSWe found that the alpha-7 nAChR agonist PHA-543613 enhanced the learning speed of feature values but did not modulate how salient distracting information was filtered from ongoing choice processes. In contrast, the selective alpha-4/beta-2 nAChR agonist ABT-089 did not affect learning speed but reduced distractibility. This dissociation was dose-dependent and evident in the absence of systematic changes in overall performance, reward intake, motivation to perform the task, perseveration tendencies, or reaction times.CONCLUSIONSThese results suggest nicotinic sub-receptor specific mechanisms consistent with (1) alpha-4/beta-2 nAChR specific amplification of cholinergic transients in prefrontal cortex linked to enhanced cue detection in light of interferences, and (2) alpha-7 nAChR specific activation prolonging cholinergic transients, which could facilitate subjects to follow-through with newly established attentional strategies when outcome contingencies change. These insights will be critical for developing function-specific drugs alleviating attention and learning deficits in neuro-psychiatric diseases.

2018-09-01·Psychopharmacology3区 · 医学

The contribution of agonist and antagonist activities of α4β2* nAChR ligands to smoking cessation efficacy: a quantitative analysis of literature data

3区 · 医学

Review

作者: Hurst, Raymond S ; Rollema, Hans

RATIONALE AND OBJECTIVETwo mechanisms underlie smoking cessation efficacies of α4β2* nicotinic acetylcholine receptor (nAChR) agonists: a "nicotine-like" agonist activity reduces craving by substituting for nicotine during a quit attempt, and a "nicotine-blocking" antagonist activity attenuates reinforcement by competing with inhaled nicotine during a relapse. To evaluate the contribution of each mechanism to clinical efficacy, we estimated the degree of agonist and antagonist activities of nicotine replacement therapy (NRT), varenicline, cytisine, and the discontinued nAChR agonists dianicline, ABT-418, ABT-089, CP-601927, and CP-601932, relative to the functional effects of nicotine from smoking.METHODSFunctional activities that occur in vivo with clinical doses were predicted from literature data on binding and functional potencies at the target α4β2 nAChR, as well as at α6β2* nAChRs, and from estimates of free drug exposures in human brain. Agonist activity is comprised of nAChR activation and desensitization, which were expressed as percentages of desensitization and activation by nicotine from smoking. Antagonist activity was expressed as the reduction in nAChR occupancy by nicotine during smoking in the presence of an agonist.RESULTSComparisons with odds ratios at end of treatment suggest that extensive α4β2 and α6β2* nAChR desensitization combined with α6β2* nAChR activation at similar levels as nicotine from smoking is associated with clinical efficacy (NRT, varenicline, cytisine, ABT-418). Effective competition with inhaled nicotine for α4β2 and α6β2* nAChRs further improves clinical efficacy (varenicline). Other discontinued nAChR agonists have lower agonist and antagonist activities at α4β2 nAChRs and are inactive or less efficacious than NRT (dianicline, ABT-089, CP-601927, CP-601932).CONCLUSIONThree pharmacological effects appear to be key factors underlying smoking cessation efficacy: the degree of activation of α6β2* nAChRs, desensitization of α4β2 and α6β2* nAChRs (agonist activity), and the reduction of nicotine occupancy at α4β2 and α6β2* nAChRs (antagonist activity). No single activity is dominant, and the level of smoking cessation efficacy depends on the profile of these activities achieved at clinical doses. While adequate agonist activity alone seems sufficient for a clinical effect (e.g., NRT, cytisine), clinical efficacy is improved with substantial competitive antagonism of α4β2 nAChRs, i.e., if the drug has a dual agonist-antagonist mechanism of action (e.g., varenicline).

2015-07-01·Alzheimer Disease & Associated Disorders4区 · 医学

Adaptive, Dose-finding Phase 2 Trial Evaluating the Safety and Efficacy of ABT-089 in Mild to Moderate Alzheimer Disease

4区 · 医学

Article

作者: Donald A. Berry ; Scott M. Berry ; Carl H. Sadowsky ; Walid M. Abi-Saab ; Shu Han ; Daniel A. Llano ; Mario D. Saltarelli ; Yili L. Pritchett ; Robert A. Lenz

ABT-089, an α4β2 neuronal nicotinic receptor partial agonist, was evaluated for efficacy and safety in mild to moderate Alzheimer disease patients receiving stable doses of acetylcholinesterase inhibitors. This phase 2 double-blind, placebo-controlled, proof-of-concept, and dose-finding study adaptively randomized patients to receive ABT-089 (5, 10, 15, 20, 30, or 35 mg once daily) or placebo for 12 weeks. The primary efficacy endpoint was the Alzheimer's Disease Assessment Scale, cognition subscale (ADAS-Cog) total score. A Bayesian response-adaptive randomization algorithm dynamically assigned allocation probabilities based on interim ADAS-Cog total scores. A normal dynamic linear model for dose-response relationships and a longitudinal model for predicting final ADAS-cog score were employed in the algorithm. Stopping criteria for futility or success were defined. The futility stopping criterion was met, terminating the study with 337 patients randomized. No dose-response relationship was observed and no dose demonstrated statistically significant improvement over placebo on ADAS-Cog or any secondary endpoint. ABT-089 was well tolerated at all dose levels. When administered as adjunctive therapy to acetylcholinesterase inhibitors, ABT-089 was not efficacious in mild to moderate Alzheimer disease. The adaptive study design enabled the examination of a broad dose range, enabled rapid determination of futility, and reduced patient exposure to nonefficacious doses of the investigational compound.

100 项与 Pozanicline Hydrochloride 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
-	Pozanicline Hydrochloride	-	DB05458

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
注意缺陷障碍伴多动	临床2期	美国	Abbott Laboratories	2006-10-01
注意缺陷障碍伴多动	临床2期	美国	Abbott Laboratories	2006-10-01
阿尔茨海默症	临床2期	美国	Abbott Laboratories	2003-07-01

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01756053 (CTgov)	临床2期	尼古丁依赖	17	ABT-089 (ABT-089)	鏇齋構淵範願鹹醖築憲(鬱鏇積憲蓋淵繭壓襯鹽) = 選齋鏇簾蓋醖構獵齋築糧糧鹹鹽網獵壓艱醖壓 (網齋膚遞齋壓積鹽顧窪, 壓淵夢獵衊觸齋獵鹹淵 ~ 築淵襯膚鹽願築願願鏇) 更多	-	2014-10-29
				Placebo (Placebo)	鏇齋構淵範願鹹醖築憲(鬱鏇積憲蓋淵繭壓襯鹽) = 夢構膚鹽築餘廠顧願鑰糧糧鹹鹽網獵壓艱醖壓 (網齋膚遞齋壓積鹽顧窪, 醖蓋餘繭範願壓範網蓋 ~ 願壓鏇遞獵築範膚鹽積) 更多