Table 4. Inhibition of rat liver tryptophan 2,3 dioxygenase activity in vitro by tianeptine and venlafaxine.

Drug	Concentration	Kynurenine formed (µmol/g wet wt of liver/h)
		Holoenzyme	Total enzyme	Apoenzyme
Tianeptine	0	1.2 ± 0.08	2.4 ± 0.18	1.2 ± 0.11
	10 µM	1.2 ± 0.10	1.7 ± 0.14*	0.5 ± 0.12**
	0.1 mM	1.2 ± 0.11	1.5 ± 0.07**	0.3 ± 0.04***
	0.5 mM	1.1 ± 0.06	1.4 ± 0.17**	0.3 ± 0.15**
	1 mM	1.0 ± 0.06	1.3 ± 0.13**	0.3 ± 0.12*
Venlafaxine	0	2.0 ± 0.32	3.1 ± 0.24	1.1 ± 0.17
	10 µM	2.2 ± 0.27	2.4 ± 0.26	0.2 ± 0.18*
	0.1 mM	2.2 ± 0.27	2.5 ± 0.14	0.3 ± 0.13*
	0.5 mM	2.3 ± 0.30	2.4 ± 0.32	0.1 ± 0.06**
	1 mM	1.9 ± 0.30	2.3 ± 0.19*	0.4 ± 0.12**

TDO activity was determined as described in the Materials and Methods either in the absence (holoenzyme activity) or presence (total enzyme activity) of added (2 µM) hematin. The apoenzyme activity was obtained by difference. Values are means ± SEM for at least three separate experiments per drug. The significance of the differences is indicated as follows: *P<0.05; **P<0.01; ***P<0.001.