NAPAMEZOLE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H16N2
Molecular Weight	212.2902
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C(C1=NCCN1)C2=CC3=C(CC2)C=CC=C3

InChI

InChIKey=WETRBJOSGIDJHQ-UHFFFAOYSA-N

InChI=1S/C14H16N2/c1-2-4-13-9-11(5-6-12(13)3-1)10-14-15-7-8-16-14/h1-4,9H,5-8,10H2,(H,15,16)

HIDE SMILES / InChI

Molecular Formula	C14H16N2
Molecular Weight	212.2902
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://adisinsight.springer.com/drugs/800000654 | https://www.ncbi.nlm.nih.gov/pubmed/1974637

Napamezole [WIN 51181] is a potent alpha-2 adrenergic receptor antagonist and a selective inhibitor of 5-hydroxytryptamine re-uptake in vitro. Napamezole was at the phase I stage of development with Sanofi Winthrop (formerly known as Sterling Drug before it was purchased by Sanofi) in the USA as a treatment for depression. The alpha adrenergic antagonist activity of napamezole was determined in vitro in rat brain receptor binding assay using [3H]clonidine and [3H]prazosin for alpha-2 and alpha-1 receptors, respectively. The Ki values for napamezole were 28 nM (alpha-2) and 93 nM (alpha-1).

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Adrenergic receptor alpha-2 113 Target ID: CHEMBL2093864 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3039138	Antagonist 2778		23.0 nM [Ki]
Adrenergic receptor alpha-1 169 Target ID: CHEMBL1907610 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3039138	Antagonist 2778		78.0 nM [Ki]

PubMed

Title	Date	PubMed
In vivo assessment of napamezole, an alpha-2 adrenoceptor antagonist and monoamine re-uptake inhibitor.	1990 Aug	1974638
Napamezole, an alpha-2 adrenergic receptor antagonist and monoamine uptake inhibitor in vitro.	1990 Aug	1974637
Potential antidepressants displayed combined alpha(2)-adrenoceptor antagonist and monoamine uptake inhibitor properties.	2001 Mar 1	11262089

Patents

Sample Use Guides

In Vivo Use Guide

The alpha-2 blocking activity of napamezole was demonstrated by its ability to: 1) antagonize clonidine-induced antinociception in mice (ED50 value, 36 mg/kg p.o.; 3 mg/kg s.c.); 2) enhance norepinephrine turnover in rat brain (minimum effective dose, 30 mg/kg p.o.); and 3) enhance locus coeruleus neuronal firing (active at doses greater than or equal to 1 mg kg i.v.) and to reverse clonidine-induced suppression of locus coeruleus firing in rats.

Route of Administration: Other

In Vitro Use Guide

The alpha adrenergic antagonist activity of napamezole was determined in vitro in rat brain receptor binding assay using [3H]clonidine and [3H]prazosin for alpha-2 and alpha-1 receptors, respectively. The Ki values for napamezole were 28 nM (alpha-2) and 93 nM (alpha-1). Napamezole also antagonized methoxamine-induced contractions (alpha-1) of the rat vas deferens with a Kb of 135 nM.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:13:50 GMT 2023` Edited by `admin` on `Fri Dec 15 16:13:50 GMT 2023`
Record UNII	GK4C2D295B
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NAPAMEZOLE

Official Name

English

napamezole [INN]

Common Name

English

1H-IMIDAZOLE, 2-((3,4-DIHYDRO-2-NAPHTHALENYL)METHYL)-4,5-DIHYDRO-

Systematic Name

English

2-((3,4-DIHYDRO-2-NAPHTHYL)METHYL)-2-IMIDAZOLINE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29713