Table 3.
General pharmacological screening of compound 7b and milrinone (M).
| Test | Dose (mg/kg) or Conc. (μg/mL) | Considered parameter | Significant criterion | 7b | M | Additional reference druga |
|---|---|---|---|---|---|---|
| MTD and Irwin testb | p.o. 300 | Number animals (died/treated) | 3/3 | nt | ||
| 100 | 3/3 | 3/3 (48h) | ||||
| 30 | 0/3 | 3/3 (48h) | ||||
| i.p. 100 | 3/3 | 3/3 | ||||
| 50 | nt | 3/3 (24h) | ||||
| 30 | 0/3 | 3/3 (48h) | ||||
| Blood pressure | p.o. 30 | Δ% after 1 and 4 h | >10% | −4/0 | nt | |
| 10 | −13/13 | |||||
| 5 | −3/−3 | |||||
| Heart rate | p.o. 30 | Δ% after 1 and 4 h | >20% | +3/+5 | +7/+8 | |
| CHCl3 arrhythmia | i.p. 30 | N° protected animals/treated | 1/3 | Lidocaine: 3/3 | ||
| 5 | >1/3 | 0/3 | Quinidine (100 mg/kg): 3/3 | |||
| Inotropismc (in vitro) | 10 | Δ% | >40% | +56 | +72 | Trequinsin: +48 |
| 3 | +31 | +60 | ||||
| 0.5 | +45 | |||||
| Chronotropism (in vitro) | 10 | Δ% | >10 | −23 | nt | Quinidine: −20; mecamylamine: −14 |
| 5 | +11 | |||||
| 3 | −10 | |||||
| 2.5 | +7 | |||||
| 1 | −3 | |||||
| Saluresis | p.o. 30 | Urine Na+ μeq treated/control | >2 | 4.5 | Furosemide (5 mg/kg): 3.0 Triamterene (2.5 mg/kg): 2.6 |
|
| 10 | 4.1 | 0.5 | ||||
| 3 | 3.4 | |||||
| Diuresis | p.o. 30 | Urine vol. treated/control | >1.5 | 2.2 | nt | Amiloride (20 mg/kg): 1.6 Hydroflumethiazide (2.5 mg/kg): 1.7 |
| 10 | 2.0 | 0.4 | ||||
| 3 | 1.8 | |||||
| Tracheal contractile tension (in vitro) | 100 | Relaxation (%) | >50% | nt | 100 | |
| 30 | 16 | nt | Theophylline: 60 | |||
| 1.0 | nt | 50 | ||||
| 0.5 | nt | 23 | ||||
| Anti-inflammatory (paw edema) | p.o. 100 | Inhibition (%) | >30% | 42 | nt | Aspirin (150 mg/kg): 40 Phenylbutazone (50 mg/kg): 33 Hydrocortisone (25 mg/kg): 32 |
| 30 | 34 | nt | ||||
| 10 | 0 | 20 | ||||
| Phenylquinone writhing | p.o. 300 | Writhing inhibition (%) | >50% | nt | 42 | Aspirin (50 mg/kg): 68 |
| 30 | 60 | nt | ||||
| 10 | 20 | nt | ||||
| Formalin algesia | p.o. 30 | Licking time reduction (%) | >50% | 89 | ntd | |
| 10 | 27 |
nt: not tested.
When not otherwise specified, the drug reference dosage corresponds to that of column 2.
MTD: maximal tolerated dose; neither significant motor stimulation nor behavioral depression were observed.
Not blocked by propranolol.
Only compounds active in the writhing test were assayed.