Classification | Drug | IC50 (μM) ± S.E. of Parameter Fita |
---|---|---|
UGT enzyme-selective inhibitors | ||
Desloratadine | 3.86 ± 0.05 | |
Fluconazole | 1136 ± 88.4 | |
Hecogenin | NI | |
(-)-Nicotine | 214 ± 2.86 | |
Niflumic acid | 168 ± 0.14 | |
Phenylbutazone | 220 ± 35.4 | |
Loratadine (desloratadine precursor) | 2.18 ± 0.34 | |
Azoles | ||
Itraconazole | NI | |
Ketoconazole | 11.9 ± 1.69 | |
Antidepressants | ||
TCAs | ||
Primary amineb | Desmethylnortriptyline | 43.7 ± 2.03 |
Didesmethylimipramine | 36.2 ± 0.40 | |
Secondary amine | Desipramine | 34.1 ± 1.04 |
Norclomipramine | 50.8 ± 4.88 | |
Nortriptyline | 45.3 ± 0.02 | |
Protriptyline | 34.3 ± 0.40 | |
Tertiary amine | Amitriptyline | 6.45 ± 0.46 |
Clomipramine | 26.0 ± 0.49 | |
Doxepin | 3.64 ± 0.16 | |
Imipramine | 42.8 ± 1.52 | |
Trimipramine | 32.6 ± 1.70 | |
Tetracyclic antidepressants | ||
Tertiary amine | Mianserin | 2.24 ± 0.11 |
Mirtazapine | 31.0 ± 0.99 | |
SSRIs | ||
Primary amine | Fluvoxamine | 224 ± 6.11 |
Secondary amine | Fluoxetine | 72.4 ± 15.8 |
Paroxetine | 63.5 ± 4.79 | |
Sertraline | 92.7 ± 8.99 | |
Tertiary amine | Citalopram | 218 ± 17.4 |
SNRIs | ||
Secondary amine | Duloxetine | 81.2 ± 8.17 |
Tertiary amine | Desvenlafaxine | 440 ± 16.5 |
Venlafaxine | NI | |
MAOIs | ||
Primary amine | Tranylcypromine | NI |
Tertiary amine | Selegiline | 67.2 ± 3.60 |
Hydrazine | Phenelzine | 94.2 ± 1.79 |
Antipsychotics | ||
Typical antipsychotics | ||
Tertiary amine | Chlorpromazine | 79.0 ± 10.7 |
Fluphenazine | 53.5 ± 6.54 | |
Haloperidol | NI | |
Loxapine | 36.0 ± 1.82 | |
Perphenazine | 66.2 ± 0.6 | |
Thioridazine | 71.3 ± 18.2 | |
Atypical antipsychotics | ||
Tertiary amine | Aripiprazole | 55.8 ± 0.80 |
Clozapine | 61.3 ± 1.40 | |
Olanzapine | 276 ± 4.49 | |
Quetiapine | 43.9 ± 7.65 |
NI, negligible inhibition over the concentration range investigated.
↵a IC50 values were calculated by fitting eq. 5 to experimental data using Enzfitter (see Materials and Methods). Each IC50 value was derived from duplicate measurements at each of four inhibitor concentrations with cotinine as the substrate (see Materials and Methods). S.E. is the standard error of the parameter fit from Enzfitter.
↵b The designation of primary, secondary, or tertiary amine or hydrazine refers to the N-containing functional group present in the side chain (aliphatic or alicyclic) attached to the mono-, bi-, tri-, or tetracyclic structure (Supplemental Fig. 1).