BRL 44408 maleate

Selective α2A-AR antagonist CAS# 681806-46-2

BRL 44408 maleate

Catalog No. BCC6948----Order now to get a substantial discount!

Product Name & Size Price Stock
BRL 44408 maleate: 5mg $92 In Stock
BRL 44408 maleate: 10mg Please Inquire In Stock
BRL 44408 maleate: 20mg Please Inquire Please Inquire
BRL 44408 maleate: 50mg Please Inquire Please Inquire
BRL 44408 maleate: 100mg Please Inquire Please Inquire
BRL 44408 maleate: 200mg Please Inquire Please Inquire
BRL 44408 maleate: 500mg Please Inquire Please Inquire
BRL 44408 maleate: 1000mg Please Inquire Please Inquire
Related Products

Quality Control of BRL 44408 maleate

Number of papers citing our products

Chemical structure

BRL 44408 maleate

3D structure

Chemical Properties of BRL 44408 maleate

Cas No. 681806-46-2 SDF Download SDF
PubChem ID 10382026 Appearance Powder
Formula C17H21N3O4 M.Wt 331.37
Type of Compound N/A Storage Desiccate at -20°C
Solubility Soluble to 100 mM in water
Chemical Name (Z)-but-2-enedioic acid;2-(4,5-dihydro-1H-imidazol-2-ylmethyl)-1-methyl-1,3-dihydroisoindole
SMILES CC1C2=CC=CC=C2CN1CC3=NCCN3.C(=CC(=O)O)C(=O)O
Standard InChIKey DDIQGSUEJOOQQQ-BTJKTKAUSA-N
Standard InChI 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-
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of BRL 44408 maleate

DescriptionSelective α2A-adrenoceptor antagonist (Ki = 1.7 nM and 144.5 nM at α2A and α2B-adrenergic receptors respectively). Increases hippocampal noradrenalin release following systemic administration. Also available as part of the α2-Adrenoceptor.

BRL 44408 maleate Dilution Calculator

Concentration (start)
x
Volume (start)
=
Concentration (final)
x
Volume (final)
 
 
 
C1
V1
C2
V2

calculate

BRL 44408 maleate Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

Preparing Stock Solutions of BRL 44408 maleate

1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 3.0178 mL 15.0889 mL 30.1777 mL 60.3555 mL 75.4444 mL
5 mM 0.6036 mL 3.0178 mL 6.0355 mL 12.0711 mL 15.0889 mL
10 mM 0.3018 mL 1.5089 mL 3.0178 mL 6.0355 mL 7.5444 mL
50 mM 0.0604 mL 0.3018 mL 0.6036 mL 1.2071 mL 1.5089 mL
100 mM 0.0302 mL 0.1509 mL 0.3018 mL 0.6036 mL 0.7544 mL
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations.

Organizitions Citing Our Products recently

 
 
 

Calcutta University

University of Minnesota

University of Maryland School of Medicine

University of Illinois at Chicago

The Ohio State University

University of Zurich

Harvard University

Colorado State University

Auburn University

Yale University

Worcester Polytechnic Institute

Washington State University

Stanford University

University of Leipzig

Universidade da Beira Interior

The Institute of Cancer Research

Heidelberg University

University of Amsterdam

University of Auckland
TsingHua University
TsingHua University
The University of Michigan
The University of Michigan
Miami University
Miami University
DRURY University
DRURY University
Jilin University
Jilin University
Fudan University
Fudan University
Wuhan University
Wuhan University
Sun Yat-sen University
Sun Yat-sen University
Universite de Paris
Universite de Paris
Deemed University
Deemed University
Auckland University
Auckland University
The University of Tokyo
The University of Tokyo
Korea University
Korea University

Background on BRL 44408 maleate

BRL 44408 maleate is a selective antagonist of α2A-adrenoceptor with Ki values of 1.7 and 144.5 nM for α2A- and α2B-adrenoceptors, respectively.

α2A-adrenoceptor is a G-protein coupled receptor. α2-adrenergic receptors include three subtypes: α2A, α2B and α2C, which play an important role in regulating neurotransmitter release from adrenergic neurons in the central nervous system and from sympathetic nerves.

BRL 44408 maleate is a selective α2A-adrenoceptor antagonist. In rat brain, BRL 44408 inhibited the binding of 5-HTIA receptor radioligands 8-OH-DPAT and RX 821002 to cortical membranes with Ki values of 199 and 338 nM respectively, which suggested that BRL 44408 recognized 5-HT1A receptor [1].

In wild type and monoamine oxidase-A knockout (MAO-A KO) mice, BRL 44408 (100 nM) inhibited the effect of dexmedetomidine, the α2 agonist. BRL 44408 (100 nM) increased evoked noradrenaline (NA) efflux in MAO-A KO mice. In wild type mice, BRL 44408 antagonized the agonist effect of dexmedetomidine with pKB value of 7.75, which inhibited locus coeruleus (LC) cell firing with EC50 value of 2.6 nM [2]. In the forced swim test, BRL 44408 reduced immobility time. In schedule-induced polydipsia assay, BRL 44408 increased adjunctive water intake, which suggested that BRL 44408 exhibited antidepressant-like response. In a visceral pain model, BRL 44408 exhibited analgesic activity [3].

References:
[1].  Meana JJ, Callado LF, Pazos A, et al. The subtype-selective alpha 2-adrenoceptor antagonists BRL 44408 and ARC 239 also recognize 5-HT1A receptors in the rat brain. Eur J Pharmacol, 1996, 312(3): 385-388.
[2].  Owesson CA, Seif I, McLaughlin DP, et al. Different alpha(2) adrenoceptor subtypes control noradrenaline release and cell firing in the locus coeruleus of wildtype and monoamine oxidase-A knockout mice. Eur J Neurosci, 2003, 18(1): 34-42.
[3].  Dwyer JM, Platt BJ, Rizzo SJ, et al. Preclinical characterization of BRL 44408: antidepressant- and analgesic-like activity through selective alpha2A-adrenoceptor antagonism. Int J Neuropsychopharmacol, 2010, 13(9): 1193-1205.

Featured Products
New Products
 

References on BRL 44408 maleate

Alpha2A- but not alpha2B/C-adrenoceptors modulate noradrenaline release in rat locus coeruleus: voltammetric data.[Pubmed:10064149]

Eur J Pharmacol. 1999 Jan 29;366(1):35-9.

In this study, we used subtype-selective antagonists 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 (2-[2H-(1-methyl-1,3-dihydroisoindole) methyl]-4,5-dihydroimidazole) at 100 nM and 1 microM significantly increased stimulated noradrenaline release, whereas the alpha2B/C-selective antagonist ARC 239 (2-[2[4-(o-methoxyphenyl)piperazin-1-yl] ethyl]-4,4dimethyl-1,3-(2H,4H)-isoquinolinedione) at 50 and 500 nM had no effect. On short stimuli (20 pulses, 200 Hz), the non-specific alpha2-adrenoceptor agonist dexmedetomidine (10 nM) significantly decreased noradrenaline release, an effect reversed by BRL 44408 (1 microM) but not by ARC 239 (500 nM). These data demonstrate that autoreceptor control of noradrenaline release in the locus coeruleus is mediated by alpha2A but not alpha2B/C-adrenoceptors.

Alpha 2C-adrenoceptors mediate contractile responses to noradrenaline in the human saphenous vein.[Pubmed:9089673]

Naunyn Schmiedebergs Arch Pharmacol. 1997 Mar;355(3):406-11.

We have investigated the subtype of alpha 2-adrenoceptor mediating isometric contractions of human saphenous vein in comparison with alpha 2-adrenoceptor ligand binding sites. Postjunctional alpha 2-adrenoceptors in the human saphenous vein were investigated in terms of the ability of alpha 2-adrenoceptor antagonists to shift the contractile potency of noradrenaline. The following antagonists were employed (potencies, pKB, in human saphenous vein in parentheses): chlorpromazine (6.98 +/- 0.24), BDF 8933 (7.60 +/- 0.06), prazosin (6.62 +/- 0.15), ARC 239 (7.19 +/- 0.15), yohimbine (7.23 +/- 0.09), HV 723 (7.52 +/- 0.14), WB 4101 (7.90 +/- 0.06), SKF 104078 (6.55 +/- 0.08), BRL 44408 (5.72 +/- 0.21). Antagonist potency at postjunctional alpha 2-adrenoceptors was correlated with antagonist affinity at alpha 2-adrenoceptor ligand binding sites in membranes of human platelet (alpha 2A), rat kidney (alpha 2B) and Sf9 cells expressing human recombinant receptors (alpha 2C), labelled with [3H]yohimbine. The correlation with the postjunctional alpha 2-adrenoceptor mediating contraction of the human saphenous vein was best for the human recombinant alpha 2C-adrenoceptor ligand binding site (r = 0.92, n = 8, P < 0.001), as compared to correlations with the alpha 2B-adrenoceptor ligand binding site of rat kidney (r = 0.62, n = 8, n.s.) and with the alpha 2A-adrenoceptor ligand binding site of human platelet (r = 0.23, n = 8, n.s.). It is concluded that the functional postjunctional alpha 2-adrenoceptor mediating contractions of the human saphenous vein closely resembles the human recombinant alpha 2C-adrenoceptor ligand binding site.

Subtype-specificity of the presynaptic alpha 2-adrenoceptors modulating hippocampal norepinephrine release in rat.[Pubmed:7796102]

Brain Res. 1995 Mar 20;674(2):238-44.

In vivo brain microdialysis and high-performance liquid chromatography with electrochemical detection were used to study the effect of different selective alpha 2-antagonists on hippocampal norepinephrine (NE) release in freely moving awake rat. Systemic administration (0.5 mg/kg i.p.) of either the alpha 2AD-antagonist BRL 44408 or the alpha 2BC-antagonist ARC 239 did not significantly change the basal release of NE. At a higher dose (5 mg/kg i.p.) ARC 239 was still ineffective, whereas BRL 4408 caused a significant increase of the extracellular level of NF. Similar results were obtained from in vitro perfusion experiments. Rat hippocampal slices were loaded with [3H]NE and the electrical stimulation-evoked release of [3H]NE was determined. The alpha 2-antagonists were applied in a concentration range of 10(-8) to 10(-6) M, ARC 239 was ineffective, whereas BRL 44408 significantly increased the electrically induced release of [3H]NE. In agreement with the data of microdialysis and perfusion experiments, BRL 44408 displaced [3H]yohimbine from hippocampal and cortical membranes of rat brain with high affinity whereas ARC 239 was less effective. The pKi values of eight different alpha 2-adrenergic compounds showed a very good correlation (r = 0.98, slope = 1.11 P < 0.0001) in hippocampus and frontal cortex have the alpha 2-adrenoceptors have been characterized as alpha 2d-subtype. Our data indicate that hippocampal NE release in rat is regulated by alpha 2D-adrenoceptors, a species variation of the human alpha 2A-subtype.

Novel alpha 2-adrenoceptor antagonists show selectivity for alpha 2A- and alpha 2B-adrenoceptor subtypes.[Pubmed:2573535]

Eur J Pharmacol. 1989 Sep 22;168(3):381-6.

Pharmacological characterization of mammalian alpha 2-adrenoceptors in various tissues and species has provided evidence for the existence of two alpha 2-adrenoceptor subtypes. These subtypes can be defined in rat and human tissues by prazosin which is alpha 2B selective and oxymetazoline which is alpha 2A selective. In addition to these agents, two types of alpha 2-adrenoceptor antagonists are described which show high affinity and selectivity for the alpha 2A-adrenoceptor and the alpha 2B-adrenoceptor respectively.

Keywords:

BRL 44408 maleate,681806-46-2,Natural Products,Adrenergic Receptor, buy BRL 44408 maleate , BRL 44408 maleate supplier , purchase BRL 44408 maleate , BRL 44408 maleate cost , BRL 44408 maleate manufacturer , order BRL 44408 maleate , high purity BRL 44408 maleate

Online Inquiry for:

      Fill out the information below

      • Size:Qty: - +

      * Required Fields

                                      Result: