MPEP is a noncompetitive, selective, potent, orally active and systemically active mGlu5 receptor antagonist, with an IC50 of 36nM for completely inhibiting quisqualate-stimulated phosphoinositide (PI) hydrolysis[1]. MPEP has anxiolytic-or antidepressant-like effects[2] and is usually used in the study of neurological disorders, such as fragile X syndrome[3] and epilepsy[4] .
In vitro, pretreatment of MN9D cells with 10μM MPEP 30min prior to rotenone exposure reversed the increase in p-PERK and γ -H2AX expression levels and alleviated the decrease in tyrosine hydroxylase induced by rotenone treatment[5] .
In vivo, intraperitoneal injection of MPEP(30mg/kg; 3days) lowered alcohol consumption during Drinking in the Dark (DID) in male and female C57BL/6 mice without changes in Homer2/Erk2 expression[6] . Intraperitoneal injection of MPEP (3 mg/kg, 30min) facilitates amphetamine-induced effects independently on the behavior measured both in naïve and in dopamine lesioned mice[7].
References:
[1] Gasparini, F., Lingenhöhl, K., Stoehr, N., Flor, P. J., Heinrich, M., Vranesic, I., Biollaz, M., Allgeier, H., Heckendorn, R., Urwyler, S., Varney, M. A., Johnson, E. C., Hess, S. D., Rao, S. P., Sacaan, A. I., Santori, E. M., Veliçelebi, G., & Kuhn, R. (1999). 2-Methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist. Neuropharmacology, 38(10), 1493–1503.
[2] Tatarczyńska, E., Klodzińska, A., Chojnacka-Wójcik, E., Palucha, A., Gasparini, F., Kuhn, R., & Pilc, A. (2001). Potential anxiolytic- and antidepressant-like effects of MPEP, a potent, selective and systemically active mGlu5 receptor antagonist. British journal of pharmacology, 132(7), 1423–1430.
[3] Castrén, M. L., & Castrén, E. (2014). BDNF in fragile X syndrome. Neuropharmacology, 76 Pt C, 729–736.
[4] Moldrich, R. X., Chapman, A. G., De Sarro, G., & Meldrum, B. S. (2003). Glutamate metabotropic receptors as targets for drug therapy in epilepsy. European journal of pharmacology, 476(1-2), 3–16.
[5] Gu, L., Luo, W. Y., Xia, N., Zhang, J. N., Fan, J. K., Yang, H. M., Wang, M. C., & Zhang, H. (2022). Upregulated mGluR5 induces ER stress and DNA damage by regulating the NMDA receptor subunit NR2B. Journal of biochemistry, 171(3), 349–359.
[6] Huang, G., Thompson, S. L., & Taylor, J. R. (2021). MPEP Lowers Binge Drinking in Male and Female C57BL/6 Mice: Relationship with mGlu5/Homer2/Erk2 Signaling. Alcoholism, clinical and experimental research, 45(4), 732–742.
[7] Managò, F., Lopez, S., Oliverio, A., Amalric, M., Mele, A., & De Leonibus, E. (2013). Interaction between the mGlu receptors 5 antagonist, MPEP, and amphetamine on memory and motor functions in mice. Psychopharmacology, 226(3), 541–550.
MPEP是一种非竞争性、选择性的、强效、有口服活性和系统活性的mGlu5受体拮抗剂，其完全抑制quisqualate 刺激的磷酸肌醇水解的IC50为36nM[1]。MPEP具有抗焦虑或抗抑郁样作用[2]，通常用于神经系统疾病的研究，如脆性X综合征[3]和癫痫[4]。
在体外，鱼藤酮处理前30min用10μM MPEP预处理MN9D细胞，逆转了鱼藤酮处理诱导的p-PERK和γ -H2AX表达水平的升高，并减轻了酪氨酸羟化酶的降低[5]。
在体内，腹腔注射MPEP(30mg/kg; 3days)降低了在暗中饮酒（DID）期间雄性和雌性C57BL/6小鼠的酒精摄入量，而没有改变Homer2/Erk2表达[6]。在对照小鼠和多巴胺损伤小鼠中，腹腔注射MPEP（3mg /kg, 30min）促进安非他命诱导的行为学效应，且不依赖于具体测量行为[7]。