Delving into the Latest Updates on Pozanicline Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Pozanicline, Pozanicline Tartrate

+ [2]

Target

CHRNA7 x nAChR α4/β2/α5 x nAChRα3&β4

Mechanism

nAChR α4/β2/α5 agonists(Nicotinic acetylcholine receptor alpha4/beta2/alpha5 agonists), α3β4 receptor antagonists(Neuronal acetylcholine receptor; alpha3/beta4 antagonists), α7 receptor agonists(Neuronal acetylcholine receptor protein alpha-7 subunit agonists)

Therapeutic Areas

Nervous System DiseasesOther Diseases

Active Indication-

Inactive Indication

Alzheimer DiseaseAttention Deficit Disorder With Hyperactivity

Originator Organization

AbbVie, Inc.

Active Organization-

Inactive Organization

Abbott Laboratories

AbbVie, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC11H16N2O

InChIKeyYRVIKLBSVVNSHF-JTQLQIEISA-N

CAS Registry161417-03-4

View All Structures (2)

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.

Start Date01 Mar 2013

Sponsor / Collaborator

University of Pennsylvania

NCT00809510 / TerminatedPhase 2

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.

Start Date01 Jan 2009

Sponsor / Collaborator

Abbott Laboratories

NCT00686933 / CompletedPhase 2

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).

Start Date01 May 2008

Sponsor / Collaborator

AbbVie, Inc.

100 Clinical Results associated with Pozanicline Hydrochloride

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100 Translational Medicine associated with Pozanicline Hydrochloride

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100 Patents (Medical) associated with Pozanicline Hydrochloride

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31

Literatures (Medical) associated with Pozanicline Hydrochloride

01 Apr 2020·PsychopharmacologyQ3 · MEDICINE

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

Q3 · MEDICINE

Article

Author: 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.

01 Sep 2018·PsychopharmacologyQ3 · MEDICINE

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

Q3 · MEDICINE

Review

Author: 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).

01 Jul 2015·Alzheimer Disease & Associated DisordersQ4 · MEDICINE

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

Q4 · MEDICINE

Article

Author: 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 Deals associated with Pozanicline Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Pozanicline Hydrochloride	-	DB05458

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Attention Deficit Disorder With Hyperactivity	Phase 2	US	Abbott Laboratories	01 Oct 2006
Attention Deficit Disorder With Hyperactivity	Phase 2	US	Abbott Laboratories	01 Oct 2006
Alzheimer Disease	Phase 2	US	Abbott Laboratories	01 Jul 2003

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01756053 (CTgov)	Phase 2	Nicotine Dependence	17	ABT-089 (ABT-089)	myxolesrmy(ipbfpjqizj) = wjndskkcig jbyqaavjrd (jephlewbna, rhllwnhvez - kposhxetvd) View more	-	29 Oct 2014
				Placebo (Placebo)	myxolesrmy(ipbfpjqizj) = rrigrsjfjs jbyqaavjrd (jephlewbna, ebdhmpwckq - xbmbtkorgf) View more
NS59910 (WPC)	Phase 2	-	-	Nicotine	cvcfwpqgps(qpebiilmgr) = chpoawvzgu ujkbmltdyo (ifrjhntdzv )	Positive	01 Oct 2013
				Varenicline	cvcfwpqgps(qpebiilmgr) = exiasasakc ujkbmltdyo (ifrjhntdzv )