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Details

Stereochemistry ABSOLUTE
Molecular Formula C15H20N2O2
Molecular Weight 260.3315
Optical Activity ( - )
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Sazetidine A

SMILES

OCCCCC#CC1=CC(OC[C@@H]2CCN2)=CN=C1

InChI

InChIKey=WONBUILDJNKYCB-AWEZNQCLSA-N
InChI=1S/C15H20N2O2/c18-8-4-2-1-3-5-13-9-15(11-16-10-13)19-12-14-6-7-17-14/h9-11,14,17-18H,1-2,4,6-8,12H2/t14-/m0/s1

HIDE SMILES / InChI
Molecular Formula C15H20N2O2
Molecular Weight 260.3315
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/27444741 | https://www.ncbi.nlm.nih.gov/pubmed/22297831 | https://www.ncbi.nlm.nih.gov/pubmed/20535453 | https://www.ncbi.nlm.nih.gov/pubmed/18719450 | https://www.ncbi.nlm.nih.gov/pubmed/20435920 | https://www.ncbi.nlm.nih.gov/pubmed/24422997

Sazetidine-A (6-[5-(azetidin-2-ylmethoxy)pyridin-3-yl]hex-5-yn-1-ol or AMOP-H-OH) is a "silent desensitizer" of neuronal nicotinic acetylcholine receptors (nAChRs), meaning that it desensitizes the receptor without first activating it. Later it was shown that Sazetidine-A is an agonist of native and recombinant alpha4beta2 nAChRs but shows differential efficacy on alpha4beta2 nAChRs subtypes. In animal models it is able to regulate the gain in body weight, alcohol and nicotine dependence. Sazetidine-A exerts analgesic, antidepressant and anxiolytic properties.

CNS Activity

Originator

Approval Year

Unknown
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
Agonist
2752
 0.64 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
The effect of sazetidine-A and other nicotinic ligands on nicotine controlled goal-tracking in female and male rats.
2017-02
Evidence for the role of β2* nAChR desensitization in regulating body weight in obese mice.
2016-11
The role of alpha5 nicotinic acetylcholine receptors in mouse models of chronic inflammatory and neuropathic pain.
2015-10-15
Sazetidine-A Activates and Desensitizes Native α7 Nicotinic Acetylcholine Receptors.
2015-10
PKCε phosphorylates α4β2 nicotinic ACh receptors and promotes recovery from desensitization.
2015-09
Pharmacologically distinct nicotinic acetylcholine receptors drive efferent-mediated excitation in calyx-bearing vestibular afferents.
2015-02-25
Decreasing nicotinic receptor activity and the spatial learning impairment caused by the NMDA glutamate antagonist dizocilpine in rats.
2014-10-15
Synthesis and pharmacological characterization of new neuronal nicotinic acetylcholine receptor ligands derived from Sazetidine-A.
2014-07-01
Selective ligand behaviors provide new insights into agonist activation of nicotinic acetylcholine receptors.
2014-05-16
Chronic sazetidine-A maintains anxiolytic effects and slower weight gain following chronic nicotine without maintaining increased density of nicotinic receptors in rodent brain.
2014-05
The unique α4+/-α4 agonist binding site in (α4)3(β2)2 subtype nicotinic acetylcholine receptors permits differential agonist desensitization pharmacology versus the (α4)2(β2)3 subtype.
2014-01
Nicotinic receptor modulation to treat alcohol and drug dependence.
2014
Effects of the sazetidine-a family of compounds on the body temperature in wildtype, nicotinic receptor β2-/- and α7-/- mice.
2013-10-15
Divergent functional effects of sazetidine-a and varenicline during nicotine withdrawal.
2013-09
Chemistry and pharmacological studies of 3-alkoxy-2,5-disubstituted-pyridinyl compounds as novel selective α4β2 nicotinic acetylcholine receptor ligands that reduce alcohol intake in rats.
2013-04-11
Effects of chronic sazetidine-A, a selective α4β2 neuronal nicotinic acetylcholine receptors desensitizing agent on pharmacologically-induced impaired attention in rats.
2013-03
Acute activation, desensitization and smoldering activation of human acetylcholine receptors.
2013
A new radioligand binding assay to measure the concentration of drugs in rodent brain ex vivo.
2012-11
Chronic sazetidine-A at behaviorally active doses does not increase nicotinic cholinergic receptors in rodent brain.
2012-11
Cholinergic receptor system as a target for treating alcohol abuse and dependence.
2012-08
Novel medication targets for the treatment of alcoholism: preclinical studies.
2012-08
Assessing the effects of chronic sazetidine-A delivery on nicotine self-administration in both male and female rats.
2012-07
Effects of sazetidine-A, a selective α4β2* nicotinic receptor desensitizing agent, on body temperature regulation in mice and rats.
2012-05-05
Discovery of isoxazole analogues of sazetidine-A as selective α4β2-nicotinic acetylcholine receptor partial agonists for the treatment of depression.
2011-10-27
Dissociation between duration of action in the forced swim test in mice and nicotinic acetylcholine receptor occupancy with sazetidine, varenicline, and 5-I-A85380.
2011-09
Sazetidine-A, a selective α4β2 nicotinic acetylcholine receptor ligand: effects on dizocilpine and scopolamine-induced attentional impairments in female Sprague-Dawley rats.
2011-06
The high-affinity nAChR partial agonists varenicline and sazetidine-A exhibit reinforcing properties in rats.
2010-12-01
Chemistry and pharmacological characterization of novel nitrogen analogues of AMOP-H-OH (Sazetidine-A, 6-[5-(azetidin-2-ylmethoxy)pyridin-3-yl]hex-5-yn-1-ol) as α4β2-nicotinic acetylcholine receptor-selective partial agonists.
2010-10-14
Nicotinic partial agonists varenicline and sazetidine-A have differential effects on affective behavior.
2010-08
Effects of sazetidine-A, a selective alpha4beta2 nicotinic acetylcholine receptor desensitizing agent on alcohol and nicotine self-administration in selectively bred alcohol-preferring (P) rats.
2010-08
Sazetidine-A is a potent and selective agonist at native and recombinant alpha 4 beta 2 nicotinic acetylcholine receptors.
2008-06
Sazetidine-A, a novel ligand that desensitizes alpha4beta2 nicotinic acetylcholine receptors without activating them.
2006-10
Patents

Patents

WO2008011484A3
3
WO2009039460A2
3
WO2009039460A3
3
WO2013071097A1
3

Sample Use Guides

In Vitro Use Guide
In the absence of PNU-120596, sazetidine-A elicited mecamylamine-sensitive increases in fluorescence in SH-SY5Y cells (EC50 4.2 µM) but no responses from primary cortical neurons. In the presence on PNU-120596, an additional response to sazetidine-A was observed in SH-SY5Y cells (EC50 0.4 µM) and robust responses were recorded in 14 % of cortical neurons.
Substance Class Chemical
Created
by admin
on Wed Apr 02 05:22:12 GMT 2025
Edited
by admin
on Wed Apr 02 05:22:12 GMT 2025
Record UNII
LH23S35NSM
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
5-Hexyn-1-ol, 6-[5-[(2S)-2-azetidinylmethoxy]-3-pyridinyl]-
Preferred Name English
Sazetidine A
Common Name English
6-[5-[(2S)-2-Azetidinylmethoxy]-3-pyridinyl]-5-hexyn-1-ol
Systematic Name English
Code System Code Type Description
EPA CompTox
DTXSID401010179
Created by admin on Wed Apr 02 05:22:12 GMT 2025 , Edited by admin on Wed Apr 02 05:22:12 GMT 2025
PRIMARY
PUBCHEM
11983356
Created by admin on Wed Apr 02 05:22:12 GMT 2025 , Edited by admin on Wed Apr 02 05:22:12 GMT 2025
PRIMARY
CAS
820231-95-6
Created by admin on Wed Apr 02 05:22:12 GMT 2025 , Edited by admin on Wed Apr 02 05:22:12 GMT 2025
PRIMARY
FDA UNII
LH23S35NSM
Created by admin on Wed Apr 02 05:22:12 GMT 2025 , Edited by admin on Wed Apr 02 05:22:12 GMT 2025
PRIMARY
WIKIPEDIA
Sazetidine A
Created by admin on Wed Apr 02 05:22:12 GMT 2025 , Edited by admin on Wed Apr 02 05:22:12 GMT 2025
PRIMARY
Related Record Type Details
Structure of Sazetidine A hydrochloride
SALT/SOLVATE -> PARENT
Structure of Sazetidine A dihydrochloride
SALT/SOLVATE -> PARENT
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