BMY 7378 is a selective antagonist of α1D-adrenergic receptor (α1D-AR) with a pki value of 8.89. It is also a mixed agonist and antagonist of serotonin 1A receptor (5-HT1A R)[1, 2]. BMY 7378 can inhibit angiotensin converting enzyme and has antihypertensive activity[3].
In vitro, BMY 7378 (10nM, 10μM) treatment of AC01 cells significantly inhibited norepinephrine (NA)-induced inositol [1,4,5] triphosphate (IP3) production[4].
In vivo, oral treatment of spontaneously hypertensive rats (SHR) with BMY 7378 (10mg/kg/day) for 4 weeks significantly reduced the blood pressure of the treated rats, improved cardiac myocyte fibrosis and cardiac hypertrophy, and increased the expression of α1D-AR protein[5]. BMY 7378 (5mg/kg) was administered to adult male hamsters via surgically implanted osmotic minipumps for 28 days, which upregulated the mRNA of 5-HT1A and 5-HT1B receptors in the hamster hypothalamus, downregulated the mRNA of 5-HT1A and monoamine oxidase-A in the brainstem, and altered the behavioral circadian rhythm of the hamsters[6].
References:
[1] Chen J. Characterisation of novel alpha1-adrenoceptor ligands[D]. UNSW Sydney, 2014.
[2] Jeffers R. The Involvement of the Intergeniculate Leaflet in the Potentiation of Photic Phase Shifts by the 5-HT1A Mixed Agonist/Antagonist BMY 7378[J]. 2013.
[3] Rodríguez J E, Andrade-Jorge E, Barquet-Nieto A, et al. BMY 7378, a selective α1D-adrenoceptor antagonist, is a new angiotensin converting enzyme inhibitor: In silico, in vitro and in vivo approach[J]. Biochimica et Biophysica Acta (BBA)-General Subjects, 2025, 1869(1): 130732.
[4] Ohmi K, Shinoura H, Nakayama Y, et al. Characterization of α1‐adrenoceptors expressed in a novel vascular smooth muscle cell line cloned from p53 knockout mice, P53LMAC01 (AC01) cells[J]. British journal of pharmacology, 1999, 127(3): 756-762.
[5] Rodríguez J E, Saucedo-Campos A D, Vega A V, et al. The α1D-adrenoreceptor antagonist BMY 7378 reverses cardiac hypertrophy in spontaneously hypertensive rats[J]. Journal of Hypertension, 2020, 38(8): 1496-1503.
[6] Vijaya Shankara J, Orr A, Mychasiuk R, et al. Chronic BMY 7378 treatment alters behavioral circadian rhythms[J]. European Journal of Neuroscience, 2017, 46(11): 2782-2790.
BMY 7378是一种α1D-肾上腺素能受体（α1D-AR）的选择性拮抗剂，pki值为8.89，也是血清素1A受体（5-HT1A R）的混合激动剂和拮抗剂[1, 2]。BMY 7378能够抑制血管紧张素转换酶，具有抗高血压活性[3]。
在体外，BMY 7378（10nM，10μM）处理AC01细胞，显著抑制了去甲肾上腺素（NA）诱导的肌醇[1,4,5]三磷酸（IP3）产生[4]。
在体内，BMY 7378（10mg/kg/day）通过口服治疗自发性高血压大鼠（SHR）4周，显著降低了治疗组大鼠的血压，改善心脏心肌细胞的纤维化和心脏肥大，增加了α1D-AR蛋白的表[5]。BMY 7378（5mg/kg）通过手术植入的渗透微型泵对成年雄性仓鼠进行给药28天，上调了仓鼠下丘脑中5-HT1A受体和5-HT1B受体的mRNA，下调了脑干中5-HT1A和单胺氧化酶-A的mRNA，改变了仓鼠的行为昼夜节律[6]。