Table 2. Characteristic new, confirmed targets that are associated with adverse drug reactions of the drugs.
Adverse drug reactions are listed that are more strongly associated with the predicted target than any known target together with pharmacokinetic data (AUC and Cmax), where available. Where pharmacokinetics (PK) and pharmacodynamic activity (PD) was available, drugs have been identified that behave comparably to the predicted drug and also cause the adverse event.
| Drug name | Target | Activity (μM) (median) | AUC [μM*h] | Cmax [μM] | Adverse event | EF ratioa | Alternative target | Comparable drugb |
|---|---|---|---|---|---|---|---|---|
| Chlorotrianisene | PTGS1 | 0.16 | NA | NA | Abdominal pain upper | 2.32 | ||
| Rash | 1.79 | |||||||
| Clemastine | SLC6A4 | 0.42 | NA | NA | Sleep disorder | 2.15 | ||
| Cyclobenzaprine | HRH1 | 0.02 | 0.16–4.10 (0.69) | 0.01–0.13 (0.06) | Ataxia | 1.73 | Desipramine | |
| Somnolence | 1.49 | Aripiprazole | ||||||
| Diphenhydramine | SLC6A3 | 4.33 | 2.57–3.42 (3.00) | 0.26–0.26 (0.26) | Tremor | 2.02/1.90 | SCN10A | Citalopram |
| Loxapine | CHRM2 | 1.12 | 0.03–0.43 (0.21) | 0.02–0.41 (0.14) | Tachycardia | 2.08/1.97 | CHRM1 | Sibutramine |
| Methylprednisolone | PGR | 1.30 | 0.09–10.76 (1.28) | 0.06–2.11 (0.31) | Depression | 3.87/2.49 | NR3C1 | Flutamide |
| Prenylamine | HRH1 | 7.87 | 0.12 | 1.2 | Sedation | 4.94 | ||
| Ranitidine | CHRM2 | 5.56 | 5.66–121.90 (9.67) | 1.14–9.11 (2.12) | Constipation | 1.63 | Haloperidol | |
| Ritodrine | OPRM1 | 9.18 | 0.03–0.32 (0.11) | 0.01–0.15 (0.04) | Hyperhidrosis | 3.21 | Oxycodone |
a
EF ratio: ADR-Target enrichment for predicted/best alternative known target.
b
Comparable drug: drugs that are known to bind the predicted target (bold: predicted target is the primary target), share the ADR and behave similarly in terms of PK and PD (see Supporting Methods).