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Details

Stereochemistry ACHIRAL
Molecular Formula C14H23N3OS
Molecular Weight 281.417
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of XANOMELINE

SMILES

CCCCCCOC1=NSN=C1C2=CCCN(C)C2

InChI

InChIKey=JOLJIIDDOBNFHW-UHFFFAOYSA-N
InChI=1S/C14H23N3OS/c1-3-4-5-6-10-18-14-13(15-19-16-14)12-8-7-9-17(2)11-12/h8H,3-7,9-11H2,1-2H3

HIDE SMILES / InChI

Molecular Formula C14H23N3OS
Molecular Weight 281.417
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Xanomeline (LY-246,708) is an orthosteric muscarinic acetylcholine receptor (mAChR) agonist, often referred to as M1/M4-preferring. It is also known to act as a M5 receptor antagonist. Xanomeline was studied in clinical trials phase I in schizophrenia. In Phase II clinical trials in Alzheimer’s patients, xanomeline significantly improved several measures of cognitive function, yet produced unwanted side effects that limited patient compliance. The side effects seem to be associated with rapid metabolism of the alkyloxy side chain following oral administration, resulting in a nonselective, yet active compound with limited therapeutic utility. Despite a second Phase II clinical trial with a patch formulation, the liabilities of xanomeline still outweigh its benefits.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
4.13 ng/mL
75 mg 2 times / day multiple, oral
XANOMELINE plasma
Homo sapiens
8.95 ng/mL
100 mg single, oral
XANOMELINE plasma
Homo sapiens
13.81 ng/mL
150 mg single, oral
XANOMELINE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
42.8 ng × h/mL
100 mg single, oral
XANOMELINE plasma
Homo sapiens
65.8 ng × h/mL
150 mg single, oral
XANOMELINE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
2.96 h
100 mg single, oral
XANOMELINE plasma
Homo sapiens
4.56 h
150 mg single, oral
XANOMELINE plasma
Homo sapiens

Doses

AEs

Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer








Drug as victim

PubMed

Patents

Sample Use Guides

In Vivo Use Guide
Xanomeline tartrate 75 mg TID, for 225 mg total daily dose Placebo, TID
Route of Administration: Oral
In Vitro Use Guide
CHO cells, stably expressing the human M5 muscarinic acetylcholine receptor were incubated for 1 h at 37°C in the absence or presence of xanomeline (1, 10, or 30 μM). Further experiments were designed to assess whether xanomeline, a partial agonist, can act as an antagonist to a full agonist at the M5 receptor. Cells were incubated for 1 h with 3 μM carbachol in the absence or in the presence of increasing concentrations of xanomeline. Xanomeline was able to antagonize the ability of carbachol to stimulate PI production in a concentration-dependent manner down to the level of maximal receptor activation by xanomeline alone.
Substance Class Chemical
Record UNII
9ORI6L73CJ
Record Status Validated (UNII)
Record Version