BRL-44408

Details

Stereochemistry	RACEMIC
Molecular Formula	C13H17N3
Molecular Weight	215.2942
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1N(CC2=NCCN2)CC3=CC=CC=C13

InChI

InChIKey=SGOFAUSEYBZKDQ-UHFFFAOYSA-N

InChI=1S/C13H17N3/c1-10-12-5-3-2-4-11(12)8-16(10)9-13-14-6-7-15-13/h2-5,10H,6-9H2,1H3,(H,14,15)

HIDE SMILES / InChI

Molecular Formula	C13H17N3
Molecular Weight	215.2942
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20047711 | https://www.ncbi.nlm.nih.gov/pubmed/8770394

BRL-44408, a potent (Ki=8.5 nM) and selective (>50-fold) α2A-adrenoceptor antagonist (KB=7.9 nM). BRL-44408 revealed antidepressant- and analgesic-like activity through selective alpha2A-adrenoceptor antagonism. Preclinical characterization of the neurochemical and behavioural profile of BRL-44408 suggests that selective antagonism of alpha2A-adrenoceptors may represent an effective treatment strategy for mood disorders and visceral pain. BRL-44408 increases hippocampal noradrenalin release following systemic administration. BRL-44408 has potential therapeutic application in the treatment of extrapyramidal side effects produced by some antipsychotic medications.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Alpha-2a adrenergic receptor 63 Target ID: CHEMBL1867 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8894622 \| https://www.ncbi.nlm.nih.gov/pubmed/8770394 \| https://www.ncbi.nlm.nih.gov/pubmed/20047711	Antagonist 2778		8.56 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Depression 235 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20047711 https://www.ncbi.nlm.nih.gov/pubmed/28507504	Primary		Preclinical	Unknown Approved Use Unknown
Sepsis 71 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19430535	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Presynaptic alpha 2-autoreceptors in brain cortex: alpha 2D in the rat and alpha 2A in the rabbit.	1993 Jul	8397342
The novel alpha-2 adrenergic radioligand [3H]-MK912 is alpha-2C selective among human alpha-2A, alpha-2B and alpha-2C adrenoceptors.	1994 Dec	7996470
A comparative study of the reversal by different alpha 2-adrenoceptor antagonists of the central sympatho-inhibitory effect of clonidine.	1996 Feb	8821553
Investigation of postjunctional alpha1- and alpha2-adrenoceptor subtypes in vas deferens from wild-type and alpha(2A/D)-adrenoceptor knockout mice.	2003 Mar	12684262

Patents

Sample Use Guides

In Vivo Use Guide

Rats: in the FST (forced swim test), acute treatment with BRL-44408 (3–30 mg/ kg i.p.) produced a significant decrease in immobility time relative to vehicle-treated animals. BRL-44408 at both 10 and 30 mg/kg significantly decreased immobility time by 30% and 49%, respectively. Acute pretreatment with BRL-44408 (1–30 mg/kg, i.p.) produced a dose-dependent reversal of PPQinduced stretching behaviour relative to vehicle. BRL-44408 at 10 and 30 mg/kg produced a significant blockade of PPQ-induced stretching by 32% and 52%, respectively.

Route of Administration: Intraperitoneal

In Vitro Use Guide

On long stimulation trains (40 pulses, 20 Hz), the alpha2A-adrenoceptor selective antagonist BRL-44408 at 100 nM and 1 uM significantly increased stimulated noradrenaline release.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 08:14:42 GMT 2023` Edited by `admin` on `Sat Dec 16 08:14:42 GMT 2023`
Record UNII	ZET7B198W2
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BRL-44408

Common Name

English

BRL 44408

Common Name

English

2-(2H-(1-METHYL-1,3-DIHYDROISOINDOLE)METHYL)-4,5-DIHYDROIMIDAZOLE

Systematic Name

English

Code System Code Type Description

CAS

118343-19-4