BRL 44408 free base · Synonyms: BRL-44408 · BRL44408

BRL-44408 is a selective, blood-brain barrier-permeable α2A-adrenergic receptor antagonist.

For research use only. Not for human or veterinary use.

Target Adrenergic Receptor p38 MAPK Dopamine Receptor ERK

Research area Cardiovascular Disease Neurological Disease

Purity >98% Stock Inquire

Data Sheet SDS COA

BRL 44408 structure

CAS No.: 118343-19-4

Download structure (.mol)

Pack sizes & pricing

Size	Price	SKU	Stock
10 mg	USD 350.00	BP-02183-10mg	In stock	Get quote
25 mg	USD 700.00	BP-02183-25mg	In stock	Get quote
50 mg	USD 1,120.00	BP-02183-50mg	In stock	Get quote
100 mg	USD 1,790.00	BP-02183-100mg	In stock	Get quote
250 mg	USD 3,580.00	BP-02183-250mg	In stock	Get quote
500 mg	USD 5,700.00	BP-02183-500mg	In stock	Get quote
1 g	Inquire	BP-02183-1g	In stock	Inquire

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Description

BRL-44408 is a selective, blood-brain barrier-permeable α2A-adrenergic receptor antagonist with a Ki value of 8.56 nM against human targets. BRL-44408 exhibits activities such as antidepressant, analgesic effects and attenuation of sepsis-induced acute lung injury by regulating the release of neurotransmitters such as norepinephrine and dopamine, or inhibiting signaling pathways including ERK1/2, p38MAPK and p65. BRL-44408 can be used in studies related to acute respiratory distress syndrome, depression and visceral pain .

Biological activity

In Vitro BRL-44408 (0-12.5 h) can inhibit the secretion of proinflammatory cytokines and the phosphorylation of ERK1/2, p38MAPK and p65 in LPS (HY-D1056)-induced NR8383 rat alveolar macrophages, with no effect on the activation of JNK or PKA. In Vivo BRL-44408 (5 mg/kg; i.p.; single administration) alleviates cecal ligation and puncture (CLP)-induced acute respiratory distress syndrome (ARDS) in rats by reducing pulmonary edema, pathological damage of lung tissues, macrophage infiltration, and proinflammatory mediator production, as well as inhibiting the activation of ERK1/2, p38MAPK and p65 signaling pathways. BRL-44408 (10 mg/kg; subcutaneous injection; single administration) significantly elevates extracellular norepinephrine (up to 204%), dopamine (up to 110%) and acetylcholine (up to 75%) levels in the medial prefrontal cortex (mPFC) of rats for at least 3.5 hours post-administration, without altering serotonin levels. BRL-44408 (3-30 mg/kg; i.p.; administered once at 24 h, 5 h and 1 h prior to testing, for a total of 3 times) exerts significant antidepressant-like effects in the forced swimming test in rats, reducing the immobility time by 30% (10 mg/kg) and 49% (30 mg/kg), while increasing the climbing time by 48% (10 mg/kg) and 107% (30 mg/kg). BRL-44408 (10-30 mg/kg; i.p.; single administration; pretreated 20 minutes before testing) exerts significant antidepressant-like effects in the rat procedure-induced polydipsia test, reducing the additional water intake by 34% (17 mg/kg) and 44% (30 mg/kg), respectively. BRL-44408 (1-30 mg/kg; i.p.; single administration; pretreated 60 minutes prior to PPQ administration) exerts significant analgesic effects in a mouse PPQ visceral pain model, reversing somatic stretching behaviors by 32% (10 mg/kg) and 52% (30 mg/kg), respectively.

Identifiers

SMILES: CC1N(CC2=NCCN2)CC3=C1C=CC=C3
InChIKey: SGOFAUSEYBZKDQ-UHFFFAOYSA-N

Specifications

MW (average): 215.2942
Formula: C₁₃H₁₇N₃
CAS No.: 118343-19-4
Physical state: Solid
Color: White to off-white
Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage: Please store the product under the recommended conditions in the Certificate of Analysis.

Documents

References

[1]. Cong Z, et al. α2A -AR antagonism by BRL-44408 maleate attenuates acute lung injury in rats with downregulation of ERK1/2, p38MAPK, and p65 pathway. J Cell Physiol. 2020;235(10):6905-6914.

[2]. Dwyer JM, 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.

[3]. Further Studies on a2-Adrenofeptor Subtypes Involved in the Modulation of [ HINoradrenaline and [3H]5-Hydroxytryptamine Release from Rat Brain Cortex Synaptosomes

Same target

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Same research area

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