LAZABEMIDE HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C8H10ClN3O.ClH
Molecular Weight	236.098
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.NCCNC(=O)C1=CC=C(Cl)C=N1

InChI

InChIKey=JMFKTFLARGGXCC-UHFFFAOYSA-N

InChI=1S/C8H10ClN3O.ClH/c9-6-1-2-7(12-5-6)8(13)11-4-3-10;/h1-2,5H,3-4,10H2,(H,11,13);1H

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/7931245
Curator's Comment: https://www.ncbi.nlm.nih.gov/pubmed/12359039 | https://www.thepharmaletter.com/article/blow-for-roche-as-phase-iii-tempium-trials-are-discontinued

Lazabemide is a reversible and selective inhibitor of monoamine oxidase B (MAO-B) that was under clinical development against Parkinson's disease, Alzheimer's disease and as an aid to smoking cessation. The development of the drug was discontinued due to liver toxicity.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Monoamine oxidase B 75 Target ID: CHEMBL2039 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24012182	Inhibitor 8504		0.091 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Alzheimer’s disease 278 Sources: http://www.europeanneuropsychopharmacology.com/article/S0924-977X(99)80017-0/abstract	Primary	Phase III 665	Unknown Approved Use Unknown
Parkinson's disease 232 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8489205	Primary	Phase III 665	Unknown Approved Use Unknown
Smoking 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12359039	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
0.44 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9056051/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	LAZABEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
0.56 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9056051/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	LAZABEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
0.95 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9056051/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	LAZABEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
0.94 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9056051/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	LAZABEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.46 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9056051/	350 mg single, oral dose: 350 mg route of administration: Oral experiment type: SINGLE co-administered:	LAZABEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
0.53 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9056051/	100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	LAZABEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
0.58 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9056051/	150 mg 2 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	LAZABEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.07 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9056051/	200 mg 2 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	LAZABEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.39 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9056051/	250 mg 2 times / day multiple, oral dose: 250 mg route of administration: Oral experiment type: MULTIPLE co-administered:	LAZABEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2.08 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9056051/	350 mg 2 times / day multiple, oral dose: 350 mg route of administration: Oral experiment type: MULTIPLE co-administered:	LAZABEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
3.3 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9056051/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	LAZABEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4.7 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9056051/	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:	LAZABEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
8.3 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9056051/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	LAZABEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
11.7 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9056051/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	LAZABEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
16.8 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9056051/	350 mg single, oral dose: 350 mg route of administration: Oral experiment type: SINGLE co-administered:	LAZABEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9056051/	100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	LAZABEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7.3 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9056051/	150 mg 2 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	LAZABEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
10.9 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9056051/	200 mg 2 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	LAZABEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
18.6 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9056051/	250 mg 2 times / day multiple, oral dose: 250 mg route of administration: Oral experiment type: MULTIPLE co-administered:	LAZABEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
29.1 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9056051/	350 mg 2 times / day multiple, oral dose: 350 mg route of administration: Oral experiment type: MULTIPLE co-administered:	LAZABEMIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
200 mg 2 times / day multiple, oral Highest studied dose Dose: 200 mg, 2 times / day Route: oral Route: multiple Dose: 200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8489205/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/8489205/	Disc. AE: ALT increased, Creatinine high... AEs leading to discontinuation/dose reduction: ALT increased (4.2%) Creatinine high (2%) Sources: https://pubmed.ncbi.nlm.nih.gov/8489205/

AEs

AE	Significance	Dose	Population
Creatinine high	2% Disc. AE	200 mg 2 times / day multiple, oral Highest studied dose Dose: 200 mg, 2 times / day Route: oral Route: multiple Dose: 200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8489205/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/8489205/
ALT increased	4.2% Disc. AE	200 mg 2 times / day multiple, oral Highest studied dose Dose: 200 mg, 2 times / day Route: oral Route: multiple Dose: 200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8489205/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/8489205/

PubMed

Title	Date	PubMed
Novel reversible monoamine oxidase A inhibitors: highly potent and selective 3-(1H-pyrrol-3-yl)-2-oxazolidinones.	2011-12-08	22017497
Up-regulation of the isoenzymes MAO-A and MAO-B in the human basal ganglia and pons in Huntington's disease revealed by quantitative enzyme radioautography.	2011-01-25	21075085
Docking studies on monoamine oxidase-B inhibitors: estimation of inhibition constants (K(i)) of a series of experimentally tested compounds.	2005-10-15	16137882
Locomotor effects of imidazoline I2-site-specific ligands and monoamine oxidase inhibitors in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway.	2004-12	15545290
SL25.1131 [3(S),3a(S)-3-methoxymethyl-7-[4,4,4-trifluorobutoxy]-3,3a,4,5-tetrahydro-1,3-oxazolo[3,4-a]quinolin-1-one], a new, reversible, and mixed inhibitor of monoamine oxidase-A and monoamine oxidase-B: biochemical and behavioral profile.	2004-09	15178694
Differential substrate specificity of monoamine oxidase in the rat heart and renal cortex.	2003-07-11	12818349
Antioxidant activity of the monoamine oxidase B inhibitor lazabemide.	2000-09-01	10927030
Safety study of lazabemide (Ro19-6327), a new MAO-B inhibitor, on cardiac arrhythmias and blood pressure of patients with Parkinson's disease.	2000-01-08	10626094
Increased density of catalytic sites and expression of brain monoamine oxidase A in humans with hepatic encephalopathy.	1997-03	9048767
Effect of lazabemide on the progression of disability in early Parkinson's disease. The Parkinson Study Group.	1996-07	8687199
Molecular neuroanatomy of human monoamine oxidases A and B revealed by quantitative enzyme radioautography and in situ hybridization histochemistry.	1996-02	9045087
Increased monoamine oxidase B activity in plaque-associated astrocytes of Alzheimer brains revealed by quantitative enzyme radioautography.	1994-09	7816197
Lazabemide (Ro 19-6327), a reversible and highly sensitive MAO-B inhibitor: preclinical and clinical findings.	1994	7931245
Monoamine oxidase B (MAO B) inhibitor therapy in Parkinson's disease: the degree and reversibility of human brain MAO B inhibition by Ro 19 6327.	1993-10	8413955
Ro 19-6327, a reversible and highly selective monoamine, oxidase B inhibitor: a novel tool to explore the MAO-B function in humans.	1990	2122653

Patents

Sample Use Guides

In Vivo Use Guide

In clinical trial against Parkinson's disease, lazabemide was administered orally at doses 25-200 mg/day

Route of Administration: Oral

In Vitro Use Guide

Lazabemide inhibited recombinant human MAO-B with IC50 of 0.091 uM.

Name

Type

Language

LAZABEMIDE MONOHYDROCHLORIDE

Preferred Name

English

LAZABEMIDE HYDROCHLORIDE

Official Name

English

LAZABEMIDE MONOHYDROCHLORIDE [MI]

Common Name

English

LAZABEMIDE HYDROCHLORIDE [USAN]

Common Name

English

RO 19-6327/001

Code

English

RO-19-6327/001

Code

English

LAZABEMIDE HCL

Common Name

English

RO-196327001

Code

English

2-PYRIDINECARBOXAMIDE, N-(2-AMINOETHYL)-5-CHLORO-, MONOHYDROCHLORIDE

Common Name

English

N-(2-AMINOETHYL)-5-CHLORO-2-PYRIDINE-CARBOXAMIDE HYDROCHLORIDE

Systematic Name

English

TEMPIUM

Brand Name

English

LAZABEMIDE HYDROCHLORIDE [JAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C667