ALVAMELINE MALEATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C9H15N5.C4H4O4
Molecular Weight	309.3211
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C/C(O)=O.CCN1N=NC(=N1)C2=CCCN(C)C2

InChI

InChIKey=YKFYFAAWVQGVTP-BTJKTKAUSA-N

InChI=1S/C9H15N5.C4H4O4/c1-3-14-11-9(10-12-14)8-5-4-6-13(2)7-8;5-3(6)1-2-4(7)8/h5H,3-4,6-7H2,1-2H3;1-2H,(H,5,6)(H,7,8)/b;2-1-

HIDE SMILES / InChI

Description
Sources: DOI: 10.1016/0024-3205(95)93724-S
Curator's Comment: description was created based on several sources, including: http://adisinsight.springer.com/drugs/800001965 | https://www.ncbi.nlm.nih.gov/pubmed/10668706

Alvameline is a partial agonist of the M1 mAChR that also displays M2/M3 antagonist effects. It readily crosses the blood-brain barrier. It has an effect profile that makes it of interest to test its ability to counteract bladder overactivity in humans. Behaviorally, alvameline has been shown to significantly improve Morris water maze (MWM) performance in both young and ageimpaired rats. It failed to improve cognition in patients with mild to moderate Alzheimer's disease.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Muscarinic acetylcholine receptor M1 169 Target ID: CHEMBL276 Sources: doi: 10.1016/0024-3205(95)93724-S	Partial Agonist 290
cholinergic receptor, muscarinic 2 7 Target ID: 1.00715344E8 Gene Symbol: Chrm2 Sources: DOI: 10.1016/0024-3205(95)93724-S	Antagonist 2778
Muscarinic acetylcholine receptor M3 159 Target ID: CHEMBL245 Sources: DOI: 10.1016/0024-3205(95)93724-S	Antagonist 2778

Conditions

Condition	Modality	Highest Phase	Product
Alzheimer’s disease 272 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10668706 https://www.ncbi.nlm.nih.gov/pubmed/9488097 https://www.ncbi.nlm.nih.gov/pubmed/9869334	Primary	Phase II 1132	Unknown Approved Use Unknown
Cognitive impairment 15 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9259007	Primary	Preclinical	Unknown Approved Use Unknown
Bladder overactivity 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11835429	Primary	Basic research	Unknown Approved Use Unknown

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9488097/	125 mg 3 times / day multiple, oral dose: 125 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ALVAMELINE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9488097/	150 mg 3 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ALVAMELINE serum	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
150 mg 3 times / day multiple, oral (unknown) MTD Dose: 150 mg, 3 times / day Route: oral Route: multiple Dose: 150 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9488097	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: Alzheimer disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/9488097	Sources: https://pubmed.ncbi.nlm.nih.gov/9488097
200 mg 3 times / day multiple, oral (unknown) Studied dose Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9488097	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: Alzheimer disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/9488097	Disc. AE: Epigastric pain... Other AEs: vomiting, Dizziness... AEs leading to discontinuation/dose reduction: Epigastric pain (severe, 1 pt) Other AEs: vomiting (severe, 1 pt) Dizziness (severe, 1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/9488097

AEs

AE	Significance	Dose	Population
Dizziness	severe, 1 pt	200 mg 3 times / day multiple, oral (unknown) Studied dose Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9488097	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: Alzheimer disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/9488097
vomiting	severe, 1 pt	200 mg 3 times / day multiple, oral (unknown) Studied dose Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9488097	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: Alzheimer disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/9488097
Epigastric pain	severe, 1 pt Disc. AE	200 mg 3 times / day multiple, oral (unknown) Studied dose Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9488097	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: Alzheimer disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/9488097

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037	substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	FMO3 67 MAO 2 CYP1A2 1054 CYP4A9/11 5 CYP2E1 667 CYP2A6 543 CYP2C19 991

Drug as victim

Target	Modality	Activity
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9884321/	likely
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9884321/	no
CYP4A9/11 5	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9884321/	no
FMO3 67	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9884321/	no
MAO 2	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9884321/	no
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9884321/	yes
CYP2A6 543	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9884321/	yes
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9884321/	yes
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9884321/	yes
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9884321/	yes

Sourcing

Vendor/Aggregator	ID	URL
BOC Sciences	120241-31-8	http://www.bocsci.com/description.asp?cas=120241-31-8
Chemspace	CSC000094528	https://chem-space.com/CSC000094528
Compound Cloud	178030
Compound Cloud	6450824
Enamine	BBV-38311169	http://www.enaminestore.com/catalog/BBV-38311169
Hangzhou Yuhao Chemical Technology	YH65699
MuseChem	I000458	https://www.musechem.com/product/I000458.html
eMolecules	110045729	https://orderbb.emolecules.com/search/#?query=110045729
eMolecules	300769792	https://orderbb.emolecules.com/search/#?query=300769792
mcule	MCULE-1835335922	https://mcule.com/MCULE-1835335922/

PubMed

Title	Date	PubMed
Lu 25-109, a combined m1 agonist and m2 antagonist, modulates regulated processing of the amyloid precursor protein of Alzheimer's disease.	1998	9869334
A bridging study of LU 25-109 in patients with probable Alzheimer's disease.	1998	9488097
In vivo muscarinic cholinergic mediated effects of Lu 25-109, a M1 agonist and M2/M3 antagonist in vitro.	1998 Jun	9683000
Lu 25-109, a muscarinic agonist, fails to improve cognition in Alzheimer's disease. Lu25-109 Study Group.	2000 Jan 25	10668706
Actions of the new antimuscarinic compound Lu 25-109 on isolated human and pig detrusor.	2002	11835429

Patents

Sample Use Guides

In Vivo Use Guide

25, 50, or 100 mg three times a day

Route of Administration: Oral

In Vitro Use Guide

Radioligand binding experiments demonstrated a small difference in affinity for Alvameline in the parotid gland compared with the bladder, the pKi values being 6.2 versus 6.5 (n=4).

Name

Type

Language

ALVAMELINE MALEATE

Official Name

English

PYRIDINE, 3-(2-ETHYL-2H-TETRAZOL-5-YL)-1,2,5,6-TETRAHYDRO-1-METHYL-, (2Z)-2-BUTENEDIOATE (1:1)

Systematic Name

English

LU 25-109-M

Code

English

ALVAMELINE MALEATE [USAN]

Common Name

English

LU-25-109-M

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C47796