Nordquist Rebecca E, Durkin Sean, Jaeschke Georg, Spooren Will
F. Hoffmann-La Roche Ltd., PRBD-N, Psychiatry Disease Area, CH-4070 Basel, Switzerland.
Eur J Pharmacol. 2007 Jul 30;568(1-3):199-202. doi: 10.1016/j.ejphar.2007.04.034. Epub 2007 Apr 30.
The mGlu5 receptor antagonist 2-methyl-6-(phenylethylnyl)-pyridine (MPEP) is highly anxiolytic in rodent models of anxiety. Recent studies showed that MPEP remains effective in some models of anxiety after repeated treatment, but tolerance may develop in other models. To further evaluate anxiolytic properties of repeated MPEP, a single administration of 3, 10, or 30 mg/kg p.o. and repeated administration of 30 mg/kg p.o. was tested in the stress-induced hyperthermia model in mice. MPEP dose-dependently inhibited stress-induced hyperthermia when given acutely. MPEP remained equally active in reducing stress-induced hyperthermia after five daily treatments with 30 mg/kg, further validating MPEP as a potential anxiolytic for chronic use.
代谢型谷氨酸受体5（mGlu5）拮抗剂2-甲基-6-（苯乙炔基）吡啶（MPEP）在啮齿类动物焦虑模型中具有高度抗焦虑作用。最近的研究表明，MPEP在重复治疗后在某些焦虑模型中仍然有效，但在其他模型中可能会产生耐受性。为了进一步评估重复给予MPEP的抗焦虑特性，在小鼠应激性体温过高模型中测试了口服3、10或30mg/kg的单次给药以及口服30mg/kg的重复给药。急性给予MPEP时，其剂量依赖性地抑制应激性体温过高。在用30mg/kg每日治疗五次后，MPEP在减轻应激性体温过高方面仍然同样有效，这进一步证实MPEP作为一种潜在的慢性抗焦虑药物的有效性。
