ALVAMELINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C9H15N5
Molecular Weight	193.2489
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCN1N=NC(=N1)C2=CCCN(C)C2

InChI

InChIKey=RNMOMKCRCIRYCZ-UHFFFAOYSA-N

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

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 168 Target ID: CHEMBL276 Sources: doi: 10.1016/0024-3205(95)93724-S	Partial Agonist 297
cholinergic receptor, muscarinic 2 7 Target ID: 1.00715344E8 Gene Symbol: Chrm2 Sources: DOI: 10.1016/0024-3205(95)93724-S	Antagonist 2849
Muscarinic acetylcholine receptor M3 160 Target ID: CHEMBL245 Sources: DOI: 10.1016/0024-3205(95)93724-S	Antagonist 2849

Conditions

Condition	Modality	Highest Phase	Product
Alzheimer’s disease 278 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 1147	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
3.7 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
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

Doses

Dose	Population	Adverse events
150 mg 3 times / day multiple, oral 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 Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/9488097	Sources: https://pubmed.ncbi.nlm.nih.gov/9488097
200 mg 3 times / day multiple, oral 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 Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN 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 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 Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/9488097
vomiting	severe, 1 pt	200 mg 3 times / day multiple, oral 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 Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/9488097
Epigastric pain	severe, 1 pt Disc. AE	200 mg 3 times / day multiple, oral 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 Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/9488097

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193	substrate 1388

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	FMO3 77 MAO 2 CYP1A2 1197 CYP4A9/11 5 CYP2E1 729 CYP2A6 626 CYP2C19 1119

Drug as victim

Target	Modality	Activity
CYP2E1 729	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/9884321/	likely
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/9884321/	no
CYP4A9/11 5	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/9884321/	no
FMO3 77	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/9884321/	no
MAO 2	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/9884321/	no
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/9884321/	yes
CYP2A6 626	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/9884321/	yes
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/9884321/	yes
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/9884321/	yes
CYP3A4 1946	substrate 4014 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
eMolecules	110045729	https://orderbb.emolecules.com/search/#?query=110045729
eMolecules	300769792	https://orderbb.emolecules.com/search/#?query=300769792
Enamine	BBV-38311169	http://www.enaminestore.com/catalog/BBV-38311169
Hangzhou Yuhao Chemical Technology	YH65699
mcule	MCULE-1835335922	https://mcule.com/MCULE-1835335922/
MuseChem	I000458	https://www.musechem.com/product/I000458.html

PubMed

Title	Date	PubMed
Actions of the new antimuscarinic compound Lu 25-109 on isolated human and pig detrusor.	2002	11835429
Lu 25-109, a muscarinic agonist, fails to improve cognition in Alzheimer's disease. Lu25-109 Study Group.	2000-01-25	10668706
In vivo muscarinic cholinergic mediated effects of Lu 25-109, a M1 agonist and M2/M3 antagonist in vitro.	1998-06	9683000
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

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

Official Name

English

LU 25-109

Preferred Name

English

Alvameline [WHO-DD]

Common Name

English

alvameline [INN]

Common Name

English

5-(2-ETHYL-2H-TETRAZOL-5-YL)-1-METHYL-1,2,3,6-TETRAHYDROPYRIDINE

Systematic Name

English

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

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C47796