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
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
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.
CNS Activity
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1907596 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19481067 |
17.0 nM [Ki] | ||
Target ID: Neuronal acetylcholine receptor; alpha6/beta2 (Mouse) Sources: https://www.ncbi.nlm.nih.gov/pubmed/19481067 |
0.11 µM [EC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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 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 | Co-administered | Analyte | Population |
---|---|---|---|---|
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 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 |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
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: 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 |
PubMed
Title | Date | PubMed |
---|---|---|
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 |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT00640185
80 mg once daily for 8 weeks
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19481067
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
Edited
Fri Dec 15 16:02:45 GMT 2023
by
admin
on
Fri Dec 15 16:02:45 GMT 2023
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Record UNII |
8CY265YM5K
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Record Status |
Validated (UNII)
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Record Version |
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NCI_THESAURUS |
C73579
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8CY265YM5K
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C80526
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24906253
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945405-37-8
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CHEMBL127071
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DTXSID90915452
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UU-62
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ACTIVE MOIETY |