Are clinically effective medicines inverse agonists?
Based on sales in the USA in 2002, a significant number of the top one hundred selling medicines target GPCRs. Those that are antagonists/inverse agonists are listed along with some examples where they have been assessed as potential inverse agonists at either the wild-type or constitutively active mutants of GPCRs.
| Generic Name (Trade Name) | Therapeutic Area | Receptor Target | Inverse Agonist? | Reference |
|---|---|---|---|---|
| Olanzapine | Antipsychotic | 5-HT2C/5-HT2A/others | Yes | Herrick-Davis et al., 2000 |
| Losartan | Cardiovascular | AT1 | Yes | Groblewski et al., 1997, Miserey-Lenkei et al., 2002 |
| Risperidone | Antipsychotic | 5-HT2/dopamine D2, D3 | Yes | Vanhauwe et al., 1999; Herrick-Davis et al., 2000 |
| Fexofenadine | Respiratory | histamine H1 | Probably | Leurs et al., 2002. |
| Clopidogrel | Thrombosis | P2Y12 | Unclear | Conley and Delaney, 2003 |
| Valsartan | Hypertension | At1 | Unclear | |
| Montelukast | Respiratory | CysLT1 | Unclear | |
| Loratidine | Respiratory | Histamine H1 | Probably | Leurs et al., 2002. |
| Quetiapine | Anti-Psychotic | Dopamine D2/5-HT2C/5HT2A | Unclear | Rauser et al., 2001 |
| Cetirizine | Respiratory | Histamine H1 | Probably | Leurs et al., 2002 |
| Metoprolol | Cardiovascular | β1-Adrenoceptor | Yes | Engelhardt et al., 2001; Levin et al., 2002 |
| Tolterodine | Genitourinary | Muscarinic M3/M2 | Unclear | |
| Famotidine | Gastrointestinal | Histamine H2 | Yes | Alewijnse et al., 1998. |