POZANICLINE TARTRATE

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 Search

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19481067 | https://www.ncbi.nlm.nih.gov/pubmed/25426579 | https://www.ncbi.nlm.nih.gov/pubmed/22795204 | http://adisinsight.springer.com/drugs/800006779

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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Neuronal acetylcholine receptor; alpha4/beta2 76 Target ID: CHEMBL1907596 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19481067	Partial Agonist 290		17.0 nM [Ki]
Neuronal acetylcholine receptor; alpha6/beta2 (Mouse) 2 Target ID: Neuronal acetylcholine receptor; alpha6/beta2 (Mouse) Sources: https://www.ncbi.nlm.nih.gov/pubmed/19481067	Partial Agonist 290		0.11 µM [EC50]

Conditions

Condition	Modality	Highest Phase	Product
Alzheimer’s disease 272 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25973909	Primary	Phase II 1132	Unknown Approved Use Unknown
Attention deficit hyperactivity disorder 68 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22795204 https://www.ncbi.nlm.nih.gov/pubmed/21748252	Primary	Phase II 1132	Unknown Approved Use Unknown
Nicotine dependence 32 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25426579	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
56.4 ng/mL REVIEW https://onlinelibrary.wiley.com/doi/abs/10.1002/(SICI)1098-2299(199705)41:1<31::AID-DDR4>3.0.CO;2-T	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 EXPERIMENT https://onlinelibrary.wiley.com/doi/abs/10.1002/(SICI)1098-2299(199705)41:1<31::AID-DDR4>3.0.CO;2-T	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21172907	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

Value	Dose	Analyte	Population
380.5 ng × h/mL REVIEW https://onlinelibrary.wiley.com/doi/abs/10.1002/(SICI)1098-2299(199705)41:1<31::AID-DDR4>3.0.CO;2-T	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 EXPERIMENT https://onlinelibrary.wiley.com/doi/abs/10.1002/(SICI)1098-2299(199705)41:1<31::AID-DDR4>3.0.CO;2-T	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21172907	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

T_1/2

Value	Dose	Analyte	Population
2.8 h REVIEW https://onlinelibrary.wiley.com/doi/abs/10.1002/(SICI)1098-2299(199705)41:1<31::AID-DDR4>3.0.CO;2-T	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 EXPERIMENT https://onlinelibrary.wiley.com/doi/abs/10.1002/(SICI)1098-2299(199705)41:1<31::AID-DDR4>3.0.CO;2-T	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 REVIEW https://onlinelibrary.wiley.com/doi/abs/10.1002/(SICI)1098-2299(199705)41:1<31::AID-DDR4>3.0.CO;2-T	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

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/21748252 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: https://pubmed.ncbi.nlm.nih.gov/21748252 Page: p.720	Sources: https://pubmed.ncbi.nlm.nih.gov/21748252 Page: p.720

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
		substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25196198/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/15179445/

PubMed

Title	Date	PubMed
Central nicotinic receptor agonists ABT-418, ABT-089, and (-)-nicotine reduce distractibility in adult monkeys.	1998 Mar	9537682
Gain of function mutation of the alpha7 nicotinic receptor: distinct pharmacology of the human alpha7V274T variant.	1999 Feb 5	10082212
Neuronal nicotinic receptor agonists for the treatment of attention-deficit/hyperactivity disorder: focus on cognition.	2007 Oct 15	17689498

Patents

Sample Use Guides

In Vivo Use Guide

80 mg once daily for 8 weeks

Route of Administration: Oral

In Vitro Use Guide

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.

Name

Type

Language

POZANICLINE TARTRATE

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