Lojková D, Mares P
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Neuropharmacology. 2005;49 Suppl 1:219-29. doi: 10.1016/j.neuropharm.2005.04.020.
Antagonists of type I of metabotropic glutamate receptors exhibit anticonvulsant action in adult as well as immature rodents. To know the anticonvulsant profile of a specific mGluR5 antagonist MPEP in developing rats, two models of epileptic seizures were used. MPEP (10, 20 or 40 mg/kg i.p.) suppressed in a dose-dependent manner epileptic afterdischarges induced by electrical stimulation of sensorimotor cortical area in three age groups (12, 18 and 25 days old). The anticonvulsant action was more expressed in the youngest group than in older animals so that in 25-day-old rats an additional dose of 80 mg/kg was used. In contrast to this marked anticonvulsant action, MPEP at a dose of 40 mg/kg i.p. in 18-day-old rat pups and at doses of 40 and 80 mg/kg in 25-day-old rat pups did not affect episodes of spike-and-wave rhythm elicited by low doses of pentetrazol. Our results delineate the profile of the anticonvulsant action of MPEP and confirm the higher efficacy of this antagonist at early developmental stages in comparison with prepubertal animals.
代谢型谷氨酸受体I型拮抗剂在成年和未成年啮齿动物中均表现出抗惊厥作用。为了解特异性mGluR5拮抗剂MPEP在发育中大鼠的抗惊厥情况，使用了两种癫痫发作模型。MPEP（10、20或40mg/kg腹腔注射）以剂量依赖性方式抑制了三个年龄组（12、18和25日龄）由感觉运动皮层区域电刺激诱发的癫痫后放电。最年幼组的抗惊厥作用比年长动物更明显，因此在25日龄大鼠中使用了额外80mg/kg的剂量。与这种明显的抗惊厥作用相反，腹腔注射40mg/kg的MPEP对18日龄幼鼠以及腹腔注射40mg/kg和80mg/kg的MPEP对25日龄幼鼠均未影响低剂量戊四氮诱发的棘波和慢波节律发作。我们的结果描绘了MPEP的抗惊厥作用情况，并证实与青春期前动物相比，该拮抗剂在发育早期阶段具有更高的疗效。
