Table 2.
Pharmacological evaluation of hydroxybupropion analogs as non-competitive nicotinic antagonistsa
| Compdb | AD50 (mg/kg) |
|||
|---|---|---|---|---|
| Tail-flickc | Hot-platec | Locomotionc | Hypothermiac | |
| 2 | 1.2 (1–1.8) | 15 (6–19) | 4.9 (0.9–46) | 9.2 (4–23) |
| (2S,3S)-4a | 0.2 (0.1–1.1) | 1.0 (0.5–4.5) | 0.9 (0.38–3.7) | 1.5 (0.95–2.6) |
| (2R,3R)-4a | 2.5 (1.7–3.5) | 10.3 (8.9–15) | IA | IA |
| 4b | IA | IA | IA | IA |
| 4c | 0.012 (0.002–0.16) | 8.6 (0.7–10.5) | IA | 4.4 (1.3–14.5) |
| 4d | 0.16 (0.05–0.6) | 4.3 (1.8–9.8) | 2.6 (0.7–10.1) | 1.7 (0.5–6.8) |
| 4e | 0.054 (0.04–0.066) | 7.6 (2–29) | IA | 2.3 (0.4–11) |
| 4f | 5.85 (3.8–8.8) | IA | IA | IA |
| 4g | 4.9 (1.6–15) | IA | IA | 4.7 (3.5–6.2) |
| 4h | 0.013 (0.005–0.03) | IA | IA | 5.67 (2.5–12.8) |
| 4i | 0.019 (0.063–0.1) | IA | IA | IA |
| 4j | 0.004 (0.002–0.012) | IA | IA | IA |
| 4k | 0.019 (0.06–0.064) | IA | IA | IA |
| 4l | 0.021 (0.005–0.1) | IA | IA | IA |
| 4m | 0.006 (0.004–0.01) | IA | IA | IA |
| 4n | 8.8 (4.3–18) | IA | IA | IA |
| 4o | 0.0056 (0.004–0.009) | IA | IA | IA |
| 4p | IA | IA | 1.9 | IA |
| 4q | 0.034 (0.001–0.1) | IA | IA | IA |
| 4r | 0.04 (0.001–0.6) | IA | IA | IA |
| 4s | 0.004 (0.001–0.03) | 3.7 (0.8–17) | 10.3 (1.4–75) | 7 (4.5–10.8) |
| 4t | 0.004 (0.001–0.03) | IA | 4.7 | IA |
| 4u | 0.016 (0.004–0.06) | IA | IA | IA |
| 4v | 0.32 (0.04–2.5) | IA | IA | IA |
| 5 | n/a | n/a | n/a | n/a |
| 6 | n/a | n/a | n/a | n/a |
a
Results were expressed as AD50 (mg/kg) ± confidence limits (CL) or % effect at the highest dose tested. Dose-response curves were determined using a minimum of four different doses of test compound, and at least eight mice were used per dose group.
b
See footnote c in Table 1.
c
n/a: not assayed; IA: AD50 > 15 mg/kg; NFT = no further testing.