Details
| Stereochemistry | RACEMIC |
| Molecular Formula | C13H17N3.C4H4O4 |
| Molecular Weight | 331.3663 |
| Optical Activity | ( + / - ) |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 1 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)\C=C/C(O)=O.CC1N(CC2=NCCN2)CC3=CC=CC=C13
InChI
InChIKey=DDIQGSUEJOOQQQ-BTJKTKAUSA-N
InChI=1S/C13H17N3.C4H4O4/c1-10-12-5-3-2-4-11(12)8-16(10)9-13-14-6-7-15-13;5-3(6)1-2-4(7)8/h2-5,10H,6-9H2,1H3,(H,14,15);1-2H,(H,5,6)(H,7,8)/b;2-1-
| Molecular Formula | C4H4O4 |
| Molecular Weight | 116.0722 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 1 |
| Optical Activity | NONE |
| 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 | ( + / - ) |
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
Curator's Comment: In rats, BRL-44408 penetrated the central nervous system resulting in peak brain and plasma concentrations of 586 ng/g and 1124 ng/ml, respectively. In the forced swim test and schedule-induced polydipsia assay, BRL-44408 produced an antidepressant-like response by dose-dependently decreasing immobility time and adjunctive water intake, respectively, while in a model of visceral pain, BRL-44408 exhibited analgesic activity by decreasing para-phenylquinone (PPQ)-induced abdominal stretching.
Originator
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| Interaction of formamidine pesticides with the presynaptic alpha(2)-adrenoceptor regulating. | 2001 May 1 |
|
| Investigation of postjunctional alpha1- and alpha2-adrenoceptor subtypes in vas deferens from wild-type and alpha(2A/D)-adrenoceptor knockout mice. | 2003 Mar |
|
| Therapeutic potential of alpha2 adrenoceptor antagonism for antipsychotic-induced extrapyramidal motor disorders. | 2009 Apr 24 |
Sample Use Guides
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
Curator's Comment: Subtype-selective antagonists were used to determine the subtype of alpha2-adrenoceptor controlling noradrenaline release in rat locus coeruleus. Noradrenaline release was measured in locus coeruleus slices using fast cyclic voltammetry at carbon fibre microelectrodes.
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
Edited
Sat Dec 16 09:12:03 GMT 2023
by
admin
on
Sat Dec 16 09:12:03 GMT 2023
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| Record UNII |
96KFS04PNM
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| Record Status |
Validated (UNII)
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| Record Version |
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96KFS04PNM
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10382026
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681806-46-2
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