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Details

Stereochemistry ABSOLUTE
Molecular Formula C11H16N2O.C4H6O6
Molecular Weight 342.3444
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of POZANICLINE TARTRATE

SMILES

O[C@H]([C@@H](O)C(O)=O)C(O)=O.CC1=NC=CC=C1OC[C@@H]2CCCN2

InChI

InChIKey=WOYZAVAGHHPUIK-LDGFUSNJSA-N
InChI=1S/C11H16N2O.C4H6O6/c1-9-11(5-3-6-12-9)14-8-10-4-2-7-13-10;5-1(3(7)8)2(6)4(9)10/h3,5-6,10,13H,2,4,7-8H2,1H3;1-2,5-6H,(H,7,8)(H,9,10)/t10-;1-,2-/m01/s1

HIDE SMILES / InChI

Molecular Formula C11H16N2O
Molecular Weight 192.2575
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula C4H6O6
Molecular Weight 150.0868
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Pozanicline is an alpha4-beta2 neuronal nicotinic receptor partial agonist. It had been in phase II clinical trials for the treatment of attention hyperactivity disorder and Alzheimer’s disease. It was tested for the treatment of schizophrenia too. All these studies were discontinued. Modulation of hippocampal learning and memory using Pozanicline in animal model was effective as novel therapeutic strategies for nicotine addiction. However future clinical trial was terminated.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
17.0 nM [Ki]
Target ID: Neuronal acetylcholine receptor; alpha6/beta2 (Mouse)
0.11 µM [EC50]
Conditions
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
56.4 ng/mL
2.93 mg/kg single, oral
dose: 2.93 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
POZANICLINE plasma
Canis lupus
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
79.6 ng/mL
2.95 mg/kg 1 times / day multiple, oral
dose: 2.95 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
POZANICLINE plasma
Canis lupus
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
575 ng/mL
1 mg/kg single, intravenous
dose: 1 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
POZANICLINE plasma
Papio anubis
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
380.5 ng × h/mL
2.93 mg/kg single, oral
dose: 2.93 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
POZANICLINE plasma
Canis lupus
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
517.7 ng × h/mL
2.95 mg/kg 1 times / day multiple, oral
dose: 2.95 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
POZANICLINE plasma
Canis lupus
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
727 ng × h/mL
1 mg/kg single, intravenous
dose: 1 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
POZANICLINE plasma
Papio anubis
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.8 h
2.93 mg/kg single, oral
dose: 2.93 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
POZANICLINE plasma
Canis lupus
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
3 h
2.95 mg/kg 1 times / day multiple, oral
dose: 2.95 mg/kg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
POZANICLINE plasma
Canis lupus
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
157 min
2 μmol/kg single, intravenous
dose: 2 μmol/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
POZANICLINE plasma
Rattus norvegicus
population: HEALTHY
age: UNKNOWN
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
40 mg 2 times / day multiple, oral
Highest studied dose
Dose: 40 mg, 2 times / day
Route: oral
Route: multiple
Dose: 40 mg, 2 times / day
Sources: Page: p.720
unhealthy, ADULT
n = 37
Health Status: unhealthy
Condition: attention deficit hyperactivity disorder
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 37
Sources: Page: p.720
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine dihydrochloride]: II. A novel cholinergic channel modulator with effects on cognitive performance in rats and monkeys.
1997 Oct
ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine]: I. A potent and selective cholinergic channel modulator with neuroprotective properties.
1997 Oct
Central nicotinic receptor agonists ABT-418, ABT-089, and (-)-nicotine reduce distractibility in adult monkeys.
1998 Mar
Gain of function mutation of the alpha7 nicotinic receptor: distinct pharmacology of the human alpha7V274T variant.
1999 Feb 5
ABT-089: pharmacological properties of a neuronal nicotinic acetylcholine receptor agonist for the potential treatment of cognitive disorders.
2004 Summer
ABT-089, a neuronal nicotinic receptor partial agonist, for the treatment of attention-deficit/hyperactivity disorder in adults: results of a pilot study.
2006 Jun 1
Neuronal nicotinic receptor agonists for the treatment of attention-deficit/hyperactivity disorder: focus on cognition.
2007 Oct 15
Glutamatergic contributions to nicotinic acetylcholine receptor agonist-evoked cholinergic transients in the prefrontal cortex.
2008 Apr 2
Selectivity of ABT-089 for alpha4beta2* and alpha6beta2* nicotinic acetylcholine receptors in brain.
2009 Oct 1
Safety and efficacy of ABT-089 in pediatric attention-deficit/hyperactivity disorder: results from two randomized placebo-controlled clinical trials.
2011 Jan
Structure-activity studies of diazabicyclo[3.3.0]octane-substituted pyrazines and pyridines as potent α4β2 nicotinic acetylcholine receptor ligands.
2011 Nov 10
Efficacy and safety of the novel α₄β₂ neuronal nicotinic receptor partial agonist ABT-089 in adults with attention-deficit/hyperactivity disorder: a randomized, double-blind, placebo-controlled crossover study.
2012 Feb
A randomized pilot study of the efficacy and safety of ABT-089, a novel α4β2 neuronal nicotinic receptor agonist, in adults with attention-deficit/hyperactivity disorder.
2012 Jun
Patents

Sample Use Guides

80 mg once daily for 8 weeks
Route of Administration: Oral
No significant stimulation was observed for Pozanicline concentrations between 1 uM and 300 uM on [3H]-ACh release from mouse interpeduncular nucleus synaptosomes indicating no agonist activity in this concentration range. Subsequently the inhibitory activity of Pozanicline on nicotine-stimulated [3H]-ACh release from mouse interpeduncular nucleus synaptosomes was tested. No inhibition of [3H]-ACh release stimulated by 30 uM nicotine was observed for simultaneous exposure of the synaptosomes to nicotine and concentrations of Pozanicline between 1 uM and 300 uM. However, inhibition was observed when the concentration of Pozanicline was increased to 1000 uM.
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:02:45 GMT 2023
Edited
by admin
on Fri Dec 15 16:02:45 GMT 2023
Record UNII
8CY265YM5K
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
POZANICLINE TARTRATE
USAN  
USAN  
Official Name English
A-87089.74
Code English
POZANICLINE TARTRATE [USAN]
Common Name English
2-Methyl-3-{[(2S)-pyrrolidin-2-yl]methoxy}pyridine (2R,3R)-2,3-dihydroxybutanedioate
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C73579
Created by admin on Fri Dec 15 16:02:45 GMT 2023 , Edited by admin on Fri Dec 15 16:02:45 GMT 2023
Code System Code Type Description
FDA UNII
8CY265YM5K
Created by admin on Fri Dec 15 16:02:45 GMT 2023 , Edited by admin on Fri Dec 15 16:02:45 GMT 2023
PRIMARY
NCI_THESAURUS
C80526
Created by admin on Fri Dec 15 16:02:45 GMT 2023 , Edited by admin on Fri Dec 15 16:02:45 GMT 2023
PRIMARY
PUBCHEM
24906253
Created by admin on Fri Dec 15 16:02:45 GMT 2023 , Edited by admin on Fri Dec 15 16:02:45 GMT 2023
PRIMARY
SMS_ID
300000044554
Created by admin on Fri Dec 15 16:02:45 GMT 2023 , Edited by admin on Fri Dec 15 16:02:45 GMT 2023
PRIMARY
CAS
945405-37-8
Created by admin on Fri Dec 15 16:02:45 GMT 2023 , Edited by admin on Fri Dec 15 16:02:45 GMT 2023
PRIMARY
ChEMBL
CHEMBL127071
Created by admin on Fri Dec 15 16:02:45 GMT 2023 , Edited by admin on Fri Dec 15 16:02:45 GMT 2023
PRIMARY
EPA CompTox
DTXSID90915452
Created by admin on Fri Dec 15 16:02:45 GMT 2023 , Edited by admin on Fri Dec 15 16:02:45 GMT 2023
PRIMARY
USAN
UU-62
Created by admin on Fri Dec 15 16:02:45 GMT 2023 , Edited by admin on Fri Dec 15 16:02:45 GMT 2023
PRIMARY
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