REDISTRIBUTION OF IMIPRAMINE FROM REGIONS OF THE BRAIN UNDER THE INFLUENCE OF CIRCULATING SPECIFIC ANTIBODIES

The kinetics of brain-to-blood redistribution of imipramine (IMI) was assessed in nine brain regions of control rats and rats given anti-tri cyclic antidepressant (anti-TCA) antibody. Two antibodies were given i ntravenously 6 min after intravenous [H-3]IMI (1 nmol/kg). One was a m urine monoclonal IgG(1) (K-a = 3.8 x 10(7) M-1) at an IgG/IMI molar ra tio of 1,000 (IgG1,000), and the other was a sheep polyclonal IgG (TAb ; K-a = 1.3 x 10(10) M-1) at IgG/IMI molar ratios of 1, 10, and 100 (T Ab1, TAb10, and TAb100). In the control rats, IMI was rapidly taken up by the brain (C-max at 5 min) with no significant differences among t he brain regions (4.1 +/- 0.4 to 5.4 +/- 0.6 pmol/g), and brain IMI th en declined monoexponentially with a half-life of 44.2 min (cerebellum ) to 77.3 min (hippocampus). The greatest IMI content was in the front al cortex and the lowest in the cerebellum. The antibodies (except TAb 1) stimulated the extent and rate of IMI redistribution from all the b rain regions depending on the immunoreactive capacity (NKa) of the ant ibody. The antibody with the highest NKa (TAb100) had the greatest eff ect. The fraction of IMI removed from the brain was 58-74%, and the re distribution half-life was 7.9-15.6 min; the mean residence time was r educed by 66-75% (11.8-23.9 min). These results demonstrate that circu lating anti-TCA IgG rapidly and reliably removes IMI from the brain, i ndicating that immunotoxicotherapy could be an efficient procedure for accelerating the removal of TCA from the brain.