Chweh A Y, Swinyard E A, Wolf H H
Neurosci Lett. 1985 Mar 15;54(2-3):173-7. doi: 10.1016/s0304-3940(85)80074-4.
gamma-Aminobutyric acid (GABA) modulation of triazolam and nicotinamide binding to benzodiazepine (BDZ) receptors in vitro was compared with the neurotoxicity and anticonvulsant activity of these two drugs in vivo. GABA had no significant effect on the inhibitory potency of triazolam in [3H]flunitrazepam receptor binding, whereas GABA decreased the inhibitory potency of nicotinamide. When administered to mice, both triazolam and nicotinamide exhibited neurotoxicity by the rotorod test and anticonvulsant activity by the pentylenetetrazol seizure threshold test. This suggests that GABA modulation of the receptor binding of a BDZ ligand in vitro is not a reliable predictor of the pharmacologic activity of the ligand.
将γ-氨基丁酸（GABA）对三唑仑和烟酰胺体外与苯二氮䓬（BDZ）受体结合的调节作用，与这两种药物在体内的神经毒性和抗惊厥活性进行了比较。GABA对三唑仑在[³H]氟硝西泮受体结合中的抑制效力没有显著影响，而GABA降低了烟酰胺的抑制效力。当给小鼠给药时，三唑仑和烟酰胺通过转棒试验均表现出神经毒性，通过戊四氮惊厥阈值试验均表现出抗惊厥活性。这表明GABA在体外对BDZ配体受体结合的调节作用并非该配体药理活性的可靠预测指标。
