BRL-54443 57477-39-1_5-HT Receptor_GPCR & G Protein_Signaling Pathways_Products

BRL 54443 (BRL54443; BRL-54443) is a potent agonist of 5-HT1E and 5-HT1F receptor with important biological activity. It suppresses 5-HT1E and 5-HT1F with pKi values of 8.7 and 9.25, respectively.

Physicochemical Properties

Molecular Formula

C14H18N2O

Molecular Weight

230.31

Exact Mass

230.141

Elemental Analysis

C, 73.01; H, 7.88; N, 12.16; O, 6.95

CAS #

57477-39-1

Related CAS #

57477-39-1

PubChem CID

2438

Appearance

White to gray solid powder

Density

1.2±0.1 g/cm3

Boiling Point

431.5±45.0 °C at 760 mmHg

Flash Point

214.8±28.7 °C

Vapour Pressure

0.0±1.1 mmHg at 25°C

Index of Refraction

1.646

LogP

1.16

Hydrogen Bond Donor Count

Hydrogen Bond Acceptor Count

Rotatable Bond Count

Heavy Atom Count

Complexity

263

Defined Atom Stereocenter Count

SMILES

O([H])C1C([H])=C([H])C2=C(C=1[H])C(=C([H])N2[H])C1([H])C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])C1([H])[H]

InChi Key

WKNFADCGOAHBPG-UHFFFAOYSA-N

InChi Code

InChI=1S/C14H18N2O/c1-16-6-4-10(5-7-16)13-9-15-14-3-2-11(17)8-12(13)14/h2-3,8-10,15,17H,4-7H2,1H3

Chemical Name

3-(1-methylpiperidin-4-yl)-1H-indol-5-ol

Synonyms

BRL 54443; BRL54443; BRL-54443

HS Tariff Code

2934.99.9001

Storage

Powder-20°C 3 years

4°C 2 years

In solvent -80°C 6 months

-20°C 1 month

Shipping Condition

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets

5-HT_1E Receptor ( Ki = 1.1 nM ); 5-HT_1F Receptor ( Ki = 0.7 nM ); 5-HT_1A Receptor ( Ki = 63 nM ); 5-HT_1B Receptor( Ki = 126 nM ); 5-HT_1D Receptor ( Ki = 63 nM );
5-HT_2A Receptor ( Ki = 1259 nM ); 5-HT_2B Receptor( Ki = 100 nM ); 5-HT_2C Receptor ( Ki = 316 nM ); 5-HT₆ Receptor ( Ki > 10000 nM ); 5-HT₇ Receptor ( Ki > 10000 nM )

ln Vitro

In vitro activity: BRL54443 binds with high affinity at 5-HT_1F receptors, despite its low affinity for other receptors, such as 5-HT_1A (63 nM), 5-HT_1B (126 nM), 5-HT_1D (63 nM), 5-HT_2A (1259 nM), 5-HT_2B (100 nM), 5-HT_2C (316 nM), 5-HT₆ (>10,000 nM), 5-HT₇ (>10,000 nM), D₂ (501 nM), D₃ (631 nM), and α_1B-adrenoceptors (1259 nM)[1].
BRL54443 specifically activates 5-HT_1E receptors in DG membranes and significantly reduces the production of cAMP that is dependent on forskolin (IC50=14 nM). Moreover, contraction is induced by BRL 54443 (-log EC50=6.52)[2].

ln Vivo

Antinociception was defined as a decrease in flinching. Rats were shown to flinch less from formalin when BRL54443 (5-HT(1E/1F); 3-300 microg/paw) was administered peripherally ipsilaterally, but not contralaterally[3].

Animal Protocol

Dissolved in distilled water containing 1 equivalent 2,3-dihydroxybutanedioic acid+0.9% NaCl; 3 μg/kg-30 mg/kg; s.c.injection

Adult male cats

References

[1]. Toward selective drug development for the human 5-hydroxytryptamine 1E receptor: a comparison of 5-hydroxytryptamine 1E and 1F receptor structure-affinity relationships. J Pharmacol Exp Ther. 2011 Jun;337(3):860-867.

[2]. Characterization of the serotonin receptor mediating contraction in the mouse thoracic aorta and signal pathway coupling. J Pharmacol Exp Ther. 2001 Apr;297(1):88-95.

[3]. Distribution of 5-ht(1E) receptors in the mammalian brain and cerebral vasculature: an immunohistochemical and pharmacological study. Br J Pharmacol. 2012 Jun;166(4):1290-302.

[4]. The role of peripheral 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E and 5-HT1F serotonergic receptors in the reduction of nociception in rats. Neuroscience. 2010 Jan 20;165(2):561-8.

Additional Infomation

3-(1-methyl-4-piperidinyl)-1H-indol-5-ol is a member of hydroxyindoles.

Solubility Data

Solubility (In Vitro)

DMSO: ~46 mg/mL (~199.7 mM)

Water: <1 mg/mL

Ethanol: ~2 mg/mL (~8.7 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (10.85 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 2.5 mg/mL (10.85 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

Solubility in Formulation 3: 30% Propylene glycol , 5% Tween 80 , 65% D5W: 30 mg/mL

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	4.3420 mL	21.7099 mL	43.4197 mL
	5 mM	0.8684 mL	4.3420 mL	8.6839 mL
	10 mM	0.4342 mL	2.1710 mL	4.3420 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

PeptideDB

BRL-54443 57477-39-1

CAS No.: 57477-39-1

Physicochemical Properties

Biological Activity

Solubility Data