2. In Vivo PD and PK Data in the Rat for the 8‑Carboxamide Derivatives 7 .
| Abbreviated
CNS PK Study (10 mg/kg PO) Tissue Concentrations
at 1 h |
Cell
Permeability P-gp Expressing LLCPK2 Cells |
||||
|---|---|---|---|---|---|
| Compound | Inhibition of Food Intake at 1 h (%) with 10 mg/kg po | Plasma (ng/mL) | Brain (ng/g) | A-B (×10–6 cm s–1) | Efflux Ratio |
| 7b | 87 | 1340 | 973 | 9.83 | 1.21 |
| 7i | 9 | 2040 | 295 | 6.05 | 2.76 |
| 7j | n.d. | n.d. | n.d. | 7.3 | 3.5 |
| 7l | 26 | n.d. | n.d. | 3.7 | 5.7 |
| 7o | n.d. | n.d. | n.d. | 12.1 | 3.5 |
| 7s | n.d. | n.d. | n.d. | 21.9 | 1.19 |
a
Mean data for n = 6 (food intake) or n = 3 (PK study) animals per time point. CNS: central nervous system; n.d.: not determined. PD: pharmacodynamic. P-gp: p-glycoprotein. PK: pharmacokinetic. PO: oral administration.