BIBP 3226 trifluoroacetate is a potent non-peptide neuropeptide Y (NPY) Y1 receptor antagonist with Ki values of 1.1, 79, and 108nM for rNPY Y1, hNPFF2, and rNPFF, respectively [1]. BIBP 3226 trifluoroacetate can bind to Y1 receptor by mimicking the C-terminal region of the native ligand NPY, and is regulation of feeding behavior and energy homeostasis [2]. BIBP 3226 trifluoroacetate has been widely used to characterize NPY receptor subtypes and to alleviate stress-induced hypertension[3].
In vitro, BIBP 3226 trifluoroacetate (30μM) treatment for 30 minutes significantly induced an increase in inositol phosphate accumulation in CHO-K1 cells expressing the human NPY Y1 receptor [4].
In vivo, BIBP 3226 trifluoroacetate via intravenous injection at a dose of 6mg/kg/h for 1.5 hours can alleviate the stress-induced tachycardia in awake spontaneously hypertensive rats[5]. In rats with spinal cord transection, a single intravenous injection of 0.5mg/kg dose of BIBP 3226 trifluoroacetate significantly inhibited the pressor response induced by exogenous NPY [6]. Intraperitoneal injection of 100μg/kg dose of BIBP 3226 trifluoroacetate every other day for 8 weeks stimulated excessive production of IL-12 in ApoE−/− mice fed with a high-fat diet and promoted the development of atherosclerosis[7].
References:
[1] Mollereau C, Gouardères C, Dumont Y, et al. Agonist and antagonist activities on human NPFF2 receptors of the NPY ligands GR231118 and BIBP3226[J]. British journal of pharmacology, 2001, 133(1): 1-4.
[2] Barreiros L, Silva E M P, Alencastre I S, et al. Determination of neuropeptide Y Y1 receptor antagonist BIBP 3226 and evaluation of receptor expression based on liquid chromatography coupled with tandem mass spectrometry[J]. Analytical and Bioanalytical Chemistry, 2020, 412(24): 6625-6632.
[3] Doods H N, Wieland H A, Engel W, et al. BIBP 3226, the first selective neuropeptide Y1 receptor antagonist: a review of its pharmacological properties[J]. Regulatory peptides, 1996, 65(1): 71-77.
[4] Vanderheyden P M L, Van Liefde I, DeBacker J P, et al. Effect of BIBP3226 on inositol phosphate accumulation and cytosolic calcium level in control and NPY Y1 receptor expressing CHO-K1 cells[J]. Regulatory peptides, 1998, 75: 191-199.
[5] Zhang W, Lundberg J M, Thorén P. Neuropeptide Y Y1 receptor antagonist (BIBP 3226) attenuates stress evoked tachycardia in conscious spontaneously hypertensive rats[J]. Cardiovascular drugs and therapy, 1997, 11(6): 801-806.
[6] Zhao X H, Sun X Y, Bergdahl A, et al. Renal and cardiovascular role of the neuropeptide Y Y1 receptor in ischaemic heart failure rats[J]. Journal of pharmacy and pharmacology, 1999, 51(11): 1257-1265.
[7] Jääskeläinen A E, Seppälä S, Kakko T, et al. Systemic treatment with neuropeptide Y receptor Y1-antagonist enhances atherosclerosis and stimulates IL-12 expression in ApoE deficient mice[J]. Neuropeptides, 2013, 47(2): 67-73.
BIBP 3226 trifluoroacetate是一种强效的非肽类neuropeptide Y (NPY) Y1 受体拮抗剂，对rNPY Y1、hNPFF2和rNPFF的Ki值分别为1.1、79和108nM[1]。BIBP 3226 trifluoroacetate可通过模拟天然配体NPY的C末端区域与 Y1 受体结合，并调节摄食行为和能量稳态[2]。BIBP 3226 trifluoroacetate已被广泛用于表征NPY受体亚型以及减轻应激诱导的高血压[3]。
在体外，30μM的BIBP 3226 trifluoroacetate处理表达人NPY Y1受体的CHO-K1细胞30分钟，显著诱导了肌醇磷酸积累的增加 [4]。
在体内，静脉注射6mg/kg/h剂量的BIBP 3226 trifluoroacetate 1.5小时，可减轻清醒自发性高血压大鼠的应激诱导的心动过速[5]。在脊髓切断大鼠中，单次静脉注射0.5mg/kg剂量的BIBP 3226 trifluoroacetate，显著抑制了外源性NPY诱导的升压反应[6]。每隔一天腹腔注射100μg/kg剂量的BIBP 3226 trifluoroacetate，持续8周，刺激了高脂饮食喂养的ApoE−/−小鼠过量产生IL-12，并促进了动脉粥样硬化的发展[7]。