BRL-44408 

BRL-44408 is a selective, blood-brain barrier-permeable α₂A-adrenergic receptor antagonist with a K_i 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^[1][2].

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^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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^[1].
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^[2].
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)^[2].
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^[2].
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^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

215.29

C₁₃H₁₇N₃

118343-19-4

CC1N(CC2=NCCN2)CC3=C1C=CC=C3

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Cong Z, et al. α_2A -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.  [Content Brief]

  [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.  [Content Brief]

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