Vergnes M, Boehrer A, Simler S, Bernasconi R, Marescaux C
Unité INSERM 398, Faculté de Médecine, Strasbourg, France.
Eur J Pharmacol. 1997 Aug 13;332(3):245-55. doi: 10.1016/s0014-2999(97)01085-6.
In Wistar rats with spontaneous non-convulsive absence epilepsy, absence seizures were dose dependently suppressed by intraperitoneal administration of the GABAB receptor antagonists CGP 36742, 50-400 mg/kg, and CGP 56999, 0.25-0.75 mg/kg, and by bilateral microinjections of the same compounds into the lateral nuclei of the thalamus. In rats susceptible to audiogenic seizures, intraperitoneal administration of both GABAB receptor antagonists, at doses which suppressed absence seizures, facilitated the elicitation of sound-induced tonic seizures. In non-epileptic control rats, intraperitoneal injections of higher doses of CGP 36742 (800-2400 mg/kg) and CGP 56999 (3-6 mg/kg) induced delayed clonic convulsions, which were suppressed by pretreatment with baclofen. c-Fos protein was expressed after GABAB receptor antagonist-induced seizures in the cortex, hippocampus, amygdala, perirhinal and piriform cortex. Intra-cortical and hippocampal microinfusion of both GABAB receptor antagonists produced focal seizures. In conclusion, GABAB receptor antagonists suppress non-convulsive absence seizures by blocking thalamic GABAB receptors, while they induce convulsions in cortical and limbic structures.
在患有自发性非惊厥性失神癫痫的Wistar大鼠中，腹腔注射GABAB受体拮抗剂CGP 36742（50 - 400毫克/千克）和CGP 56999（0.25 - 0.75毫克/千克）以及将相同化合物双侧微量注射到丘脑外侧核中，失神发作呈剂量依赖性受到抑制。在对声源性惊厥敏感的大鼠中，腹腔注射两种GABAB受体拮抗剂，在抑制失神发作的剂量下，促进了声音诱发的强直性惊厥的诱发。在非癫痫对照大鼠中，腹腔注射较高剂量的CGP 36742（800 - 2400毫克/千克）和CGP 56999（3 - 6毫克/千克）会诱发延迟性阵挛性惊厥，而巴氯芬预处理可抑制这种惊厥。在GABAB受体拮抗剂诱发的惊厥后，皮质、海马、杏仁核、梨状前皮质和梨状皮质中表达了c-Fos蛋白。皮质内和海马内微量注射两种GABAB受体拮抗剂均会产生局灶性惊厥。总之，GABAB受体拮抗剂通过阻断丘脑GABAB受体来抑制非惊厥性失神发作，同时它们在皮质和边缘结构中诱发惊厥。
