Table 1.
Pharmacological activities of P450 and epoxygenase inhibitors
| Compound | Ki (nM ± SEM) | IC50 (95% C.I.) icv nmol |
|||||
|---|---|---|---|---|---|---|---|
| μ opioid a | δ opioid b | κ opioid c | H3d | CYP2C19 | Leukocyte 12-LOX e |
Est. Anti- Analgesicf |
|
| CC12 g | 7.1 × 103 | > 104 | ~ 104 | 22 | 19.9 | > 104 | 66.6 (43.8-89.4) |
| Miconazole | 1,400 ± 65 | 590 ± 29 | 760 ± 120 | 4,467 ± 447 | 23.7 g | > 104 | 0.2 |
| Sulconazole | 1,100 ± 36 | 690 ± 44 | 960 ± 51 | 31.0 | |||
| Clotrimazole | 96 ± 6.4 | 770 ± 25 | 260 ± 8.7 | 316 | |||
| Fluconazole | > 104 | > 104 | > 104 | > 104 | 1,050 g | 0.02 | |
| Ketoconazole | > 104 | > 104 | > 104 | 1,800 | |||
| MW06-25 g | > 104 | > 104 | > 104 | > 104 | 19.1 | > 104 h | 5.4 (2.1-8.7) |
| MS-PPOH | > 104 | > 104 | > 104 | 22.2 × 103 | > 104 g | 0.007 (0.002 – 0.012) |
|
Ki values for receptors were calculated from percent inhibition of binding from three experiments performed in triplicate. The solvent used for all receptor studies (1% DMSO) had no effect when tested alone.
a
[3H]DAMGO binding
b
[3H]Naltrindole binding
c
[3H]U69,593 binding
d
[3H]-Nα-methylhistamine binding
e
AA 12-lipoxygenase
f
In vivo IC50 values estimated by regression from Fig. 4 as described in Methods
g
Data from [4]
h
MW06-25 also had no effect (Ki > 10 μM) on cyclooxygenase-1, cyclooxygenase-2, and platelet 12-lipoxygenase [4].