Ragusi C, Scherrmann J M, Harrison K, Smith D S, Rips R, Boschi G
INSERM U26, Hôpital Fernand Widal, Paris, France.
J Neurochem. 1998 May;70(5):2099-105. doi: 10.1046/j.1471-4159.1998.70052099.x.
The kinetics of brain-to-blood redistribution of imipramine (IMI) was assessed in nine brain regions of control rats and rats given anti-tricyclic antidepressant (anti-TCA) antibody. Two antibodies were given intravenously 6 min after intravenous [3H]IMI (1 nmol/kg). One was a murine monoclonal IgG1 (Ka = 3.8 x 10(7) M(-1)) at an IgG/IMI molar ratio of 1,000 (IgG1,000), and the other was a sheep polyclonal IgG (TAb; Ka = 1.3 x 10(10) M(-1)) at IgG/IMI molar ratios of 1, 10, and 100 (TAb1, TAb10, and TAb100). In the control rats, IMI was rapidly taken up by the brain (Cmax at 5 min) with no significant differences among the brain regions (4.1 +/- 0.4 to 5.4 +/- 0.6 pmol/ g), and brain IMI then declined monoexponentially with a half-life of 44.2 min (cerebellum) to 77.3 min (hippocampus). The greatest IMI content was in the frontal cortex and the lowest in the cerebellum. The antibodies (except TAb1) stimulated the extent and rate of IMI redistribution from all the brain regions depending on the immunoreactive capacity (NKa) of the antibody. The antibody with the highest NKa (TAb100) had the greatest effect. The fraction of IMI removed from the brain was 58-74%, and the redistribution half-life was 7.9-15.6 min; the mean residence time was reduced by 66-75% (11.8-23.9 min). These results demonstrate that circulating anti-TCA IgG rapidly and reliably removes IMI from the brain, indicating that immunotoxicotherapy could be an efficient procedure for accelerating the removal of TCA from the brain.
在对照大鼠和给予抗三环类抗抑郁药（抗TCA）抗体的大鼠的九个脑区中评估了丙咪嗪（IMI）的脑-血再分布动力学。静脉注射[³H]IMI（1 nmol/kg）6分钟后静脉注射两种抗体。一种是鼠单克隆IgG1（Ka = 3.8 x 10⁷ M⁻¹），IgG/IMI摩尔比为1000（IgG1000），另一种是绵羊多克隆IgG（TAb；Ka = 1.3 x 10¹⁰ M⁻¹），IgG/IMI摩尔比为1、10和100（TAb1、TAb10和TAb100）。在对照大鼠中，IMI迅速被脑摄取（5分钟时达到Cmax），脑区之间无显著差异（4.1±0.4至5.4±0.6 pmol/g），然后脑内IMI呈单指数下降，半衰期为44.2分钟（小脑）至77.3分钟（海马体）。IMI含量最高的是额叶皮质，最低的是小脑。抗体（除TAb1外）根据抗体的免疫反应能力（NKa）刺激了IMI从所有脑区的再分布程度和速率。NKa最高的抗体（TAb100）效果最大。从脑中去除的IMI比例为58 - 74%，再分布半衰期为7.9 - 15.6分钟；平均驻留时间减少了66 - 75%（11.8 - 23.9分钟）。这些结果表明，循环抗TCA IgG能快速、可靠地从脑中去除IMI，表明免疫毒素疗法可能是加速从脑中去除TCA的有效方法。
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