Galpern W R, Miller L G, Greenblatt D J, Szabo G K, Browne T R, Shader R I
Department of Psychiatry, Tufts University School of Medicine, Boston MA.
Biochem Pharmacol. 1991 Dec 11;42 Suppl:S99-104. doi: 10.1016/0006-2952(91)90398-o.
Clinical studies suggest that carbamazepine may attenuate effects of alprazolam discontinuation. Since discontinuation of chronic alprazolam in a mouse model is associated with behavioral alterations and upregulation at the gamma-aminobutyric acidA (GABAA) receptor, we studied the effects of carbamazepine administration after alprazolam (2 mg/kg/day) discontinuation. Open-field activity was increased in mice 4 days after alprazolam discontinuation, but this effect was reduced significantly by continuous infusion of carbamazepine, 25 or 100 mg/kg/day. Benzodiazepine receptor binding in vivo was increased in cortex at 2 and 4 days after alprazolam discontinuation, and in hypothalamus at 4 days; with carbamazepine, 100 mg/kg/day, binding in both regions at these time points was similar to control values. Similar results were observed in cortex with benzodiazepine receptor binding in vitro. GABA-dependent chloride uptake was also increased at 4 days alprazolam administration. Treatment with carbamazepine attenuated (P less than 0.10) this increase. Carbamazepine alone after vehicle did not alter benzodiazepine binding or GABA-dependent chloride uptake. These results indicate that carbamazepine administration after alprazolam discontinuation attenuates behavioral and neurochemical alterations associated with discontinuation.
临床研究表明，卡马西平可能会减轻阿普唑仑停药的影响。由于在小鼠模型中慢性阿普唑仑停药与行为改变及γ-氨基丁酸A（GABAA）受体上调有关，我们研究了阿普唑仑（2毫克/千克/天）停药后给予卡马西平的效果。阿普唑仑停药4天后，小鼠的旷场活动增加，但持续输注25或100毫克/千克/天的卡马西平可显著降低这种效果。阿普唑仑停药后第2天和第4天，皮质中的苯二氮䓬受体结合增加，第4天下丘脑的受体结合增加；给予100毫克/千克/天的卡马西平后，这两个区域在这些时间点的结合与对照值相似。在体外皮质中苯二氮䓬受体结合方面也观察到了类似结果。阿普唑仑给药4天时，GABA依赖性氯摄取也增加。卡马西平治疗可减轻（P<0.10）这种增加。给予赋形剂后单独使用卡马西平不会改变苯二氮䓬结合或GABA依赖性氯摄取。这些结果表明，阿普唑仑停药后给予卡马西平可减轻与停药相关的行为和神经化学改变。
