Table 2.
Pharmacological evaluation of 3,5,5-trimethylmorpholine analogs as non-competitive nicotinic antagonistsa,b
| Compd | AD50 (mg/kg) | ||||
|---|---|---|---|---|---|
| Tail-flick | Hot-plate | Locomotion | Hypothermia | CPP | |
| 2c | 1.2 (1–1.18) | 15 (6–19) | 4.9 (0.9–46) | 9.2 (4–23) | 0.35 |
| (S,S)-4ac | 0.2 (0.06–0.7) | 1.0 (0.2–2.2) | 0.9 (0.2–5.7) | 1.5 (0.15–2.6) | 0.1 |
| (R,R)-4ac | 2.5 (1.2–3.6) | 10.3 (5.7–17.1) | IA | IA | NT |
| (S,S)-5a | 0.036 (0.012–0.1) | IA | IA | IA | NT |
| (R,R)-5a | 1.26 (0.39–4.1) | 3.9 (0.8–19) | IA | IA | NT |
| (S,S)-5b | 0.02 (0.008–0.03) | IA | 4.7 (1.2–19) | IA | NT |
| (S,S)-5c | 0.006 (0.003–0.01) | IA | 2.1 (0.9–4.8) | IA | NT |
| (S,S)-5d | 0.13 (0.03–0.6) | IA | 3.8 (1.2–12) | IA | NT |
| (S,S)-5e | 0.029 (0.004–0.23) | IA | IA | IA | 0.025 |
| (S,S)-5f | 0.056 (0.018–0.17) | IA | IA | IA | 0.03 |
| (S,S)-5g | 0.018 (0.009–0.03) | 9.6 (1.2–77) | 2.7 (0.7–10.5) | 2.5 (1.6–3.9) | NT |
| (S,S)-5h | 0.017 (0.002–0.15) | IA | 0.49(0.3–6.6) | IA | NT |
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. IA = AD50 > 20 mg/kg.
b
NT = not tested.
c
Taken from reference 13.