ED50 values (95% CL; milligrams per kilogram) of R116301 and reference NK1 receptor antagonists for inhibition of SP-induced extravasation in guinea-pigs
| Compound | Route | Time | ED50 (95% Confidence Limits) | ||
|---|---|---|---|---|---|
| Nose | Paws | Conjunctiva | |||
| h | mg/kg | ||||
| R116301 | s.c. | 1 | 0.097 (0.072–0.13) | 0.11 (0.091–0.14) | 0.085 (0.057–0.13) |
| p.o. | 1 | 0.26 (0.17–0.38) | 0.26 (0.17–0.38) | 0.29 (0.22–0.40) | |
| 16 | 0.68 (0.42–1.1) | 0.68 (0.42–1.1) | 1.5 (1.0–2.3) | ||
| i.v. | 5 min | 0.11 (0.075–0.17) | 0.074 (0.055–0.10) | 0.042 (0.031–0.058) | |
| GR-203040 | s.c. | 1 | 0.0031 (0.0023–0.0042) | 0.0041 (0.0030–0.0055) | 0.0024 (0.0017–0.0032) |
| p.o. | 1 | 0.59 (0.43–0.79) | 0.67 (0.45–1.0) | 0.59 (0.43–0.79) | |
| Nolpitantium | s.c. | 1 | 0.050 (0.023–0.0042)1-a | 0.050 (0.023–0.11)1-a | 0.050 (0.023–0.11)1-a |
| s.c. | 4 | >0.16 | >0.16 | >0.16 | |
| p.o. | 1 | >2.5 | >2.5 | >2.5 | |
| Aprepitant | s.c. | 1 | 0.028 (0.023–0.035) | 0.032 (0.024–0.044) | 0.028 (0.023–0.035) |
| p.o. | 1 | 0.085 (0.063–0.11) | 0.13 (0.086–0.19) | 0.064 (0.048–0.087) | |
| L-760735 | s.c. | 1 | 0.056 (0.046–0.070) | 0.065 (0.048–0.088) | 0.065 (0.048–0.088) |
| CP-99994 | s.c. | 1 | 0.17 (0.12–0.23) | 0.17 (0.12–0.23) | 0.17 (0.12–0.23) |
| p.o. | 1 | 21 (16–29) | 25 (18–33) | 25 (18–33) | |
| CGP-49823 | s.c. | 1 | 0.31 (- - -)1-a | 0.31 (- - -)1-a | 0.31 (- - -)1-a |
| CP-96345 | s.c. | 1 | 0.22 (0.18–0.28) | 0.19 (0.14–0.26) | 0.59 (0.43–0.80) |
| p.o. | 1 | 2.7 (1.7–4.3) | 2.3 (1.4–3.8) | 3.6 (2.2–5.7) | |
| p.o. | 4 | >10 | >10 | >10 | |
| p.o. | 16 | >40 | >40 | >40 | |
| SDZ-NKT-343 | i.p. | 1 | 2.5 (- - -)1-a | 2.5 (- - -)1-a | 2.5 (- - -)1-a |
| p.o. | 1 | >10 | >10 | >10 | |
| MDL-103392 | s.c. | 1 | 5.4 (3.6–8.0) | >10 | 8.1 (5.4–12) |
| RP-67580 | s.c. | 1 | 10 (- - -)1-a | 10 (- - -)1-a | ≥10 |
↵1-a ED50 estimated with only two to three instead of five animals per dose level.