Activity of ADX71743 and olanzapine in the DOI-induced head twitches test in mice together with the measured plasma, CSF concentrations and CSF concentration/IC50 (in vitro) of ADX71743 in mice at the end of the experiment
CSF exposure was calculated from the plasma exposure using mice plasma protein binding (fu = 4.4%).
| Pretreatment | Dose | Route | Animal | DOI-Induced Twitches | Plasma Exposure | CSF Exposure | CSF/EC50 (In Vitro) | ||
|---|---|---|---|---|---|---|---|---|---|
| mg/kg | n | mean ± S.E.M. | ng/ml | nM | ng/ml | nM | |||
| CD/saline | 0/0 | s.c./i.p. | 8 | 0.7 ± 0.3 | |||||
| CD/DOI | 0/3 | s.c./i.p. | 8 | 23.1 ± 1.8 | |||||
| ADX71743/DOI | 50/3 | s.c./i.p. | 8 | 18.1 ± 1.6 | 3233 | 12,007 | 142 | 528 | 4 |
| ADX71743/DOI | 100/3 | s.c./i.p. | 8 | 21.1 ± 1.5 | 4273 | 15,865 | 188 | 698 | 6 |
| ADX71743/DOI | 150/3 | s.c./i.p. | 8 | 21.8 ± 2.0 | 6311 | 23,436 | 278 | 1031 | 8 |
| Olanzapine/DOI | 0.1/3 | p.o./i.p. | 8 | 5.0 ± 0.4*** | |||||
↵*** P < 0.001 compared with corresponding vehicle.