Table 1.
Drugs tested in the clinical trials included in the review and mechanisms of actions
| Class and proposed mechanism of action | Drug | Studies |
|---|---|---|
| Anti-amyloid | ||
| Reduced amyloid beta aggregation or oligomerization | Tramiprosate (3APS) | 3 phase III |
| Increased amyloid beta clearance, active immunotherapy | AN1792 | 1 phase II |
| Sodium oligo-mannurarate | 1 phase II, 1 phase III | |
| Increased amyloid beta clearance, passive immunotherapy | Solanezumab | 3 phase III |
| Bapineuzumab | 1 phase II, 4 phase III | |
| Gantenerumab | 2 phase III | |
| BAN2401 | 1 phase II | |
| Crenezumab | 1 phase II | |
| Aducanumab | 2 phase III | |
| Immunoglobulin | 1 phase II, 3 phase III | |
| Increased amyloid beta clearance, other | Clioquinol (PBT-1) | 1 phase II |
| Reduced amyloid beta production, gamma secretase inhibitor | Semagacestat | 2 phase II, 2 phase III |
| Reduced amyloid beta production, gamma secretase modulator | Tarenflurbil | 1 phase II, 2 phase III |
| Reduced amyloid beta production, beta secretase inhibitor | MK-8931 | 1 phase II/III, 1 phase III |
| AZD3293 (LY3314814) | 1 phase II/III | |
| E2609 | 1 phase II | |
| Glycation end products receptor (RAGE) inhibitors | Azeliragon (TTP 488) | 1 phase II, 1 phase III |
| Reduced amyloid beta | Nilvadipine | 1 phase III |
| Statins | 1 phase II, 2 phase III | |
| Anti-tau | ||
| Aggregation inhibitor | TRx0237 (formerly TRx0014) | 1 phase II, 2 phase III |
| Tideglusib | 1 phase II | |
| Modulators of blood glucose | ||
| Insulins | 4 phase II, 1 phase II/III | |
| Rosiglitazone | 1 phase II, 3 phase III | |
| Pioglitazone | 2 phase II | |
| AC 1204 | 2 phase II/III | |
| Phosphodiesterase inhibitors | ||
| Phosphodiesterase 9A | PF-04447943 | 1 phase II |
| BI 409306 | 2 phase II | |
| Phosphodiesterase 5 | Udenafil | 1 phase III |
| Phosphodiesterase 4 | MK 0952 | 1 phase II |
| Histamine modulators | ||
| GSK239512 | 1 phase II | |
| MK0249 | 1 phase II | |
| ABT 288 | 1 phase II | |
| Nizatidine | 1 phase ? | |
| SAR110894D | 1 phase II | |
| S38093 | 2 phase II | |
| Nicotine modulators | ||
| Nicotinic acetylcholine receptor partial agonist | ABT-089 | 2 phase II |
| RO5313534 | 1 phase II | |
| EVP-6124 | 1 phase II, 2 phase III | |
| Varenicline | 1 phase II | |
| AZD3480 | 2 phase II | |
| AQW051 | 1 phase II | |
| α-7 nicotinic acetylcholine receptor allosteric modulator | ABT-126 | 3 phase II |
| Muscarine modulators | ||
| Allosteric modulator | MK 7622 | 1 phase II |
| Allosteric modulator | Lu25-109 | 1 study ? |
| Non-selective muscarinic acetylcholine receptor agonist | Talsaclidine | 2 phase II |
| Serotonin modulators | ||
| 5-hydroxytryptamine 6 receptor antagonist | SB 742457 | 4 phase II |
| Lu AE58054 | 1 phase II, 2 phase III | |
| SAM-531 | 1 phase II | |
| 5-hydroxytryptamine 1A receptor agonist | Xaliproden | 2 phase III |
| Palirodena | 1 phase II | |
| 5-hydroxytryptamine 1 receptor antagonist | Lecozotan | 1 phase II, 1 phase II/III |
| 5-hydroxytryptamine 4 receptor agonist | PRX-03140 | 2 phase II |
| Other central nervous system transmitter modulators | ||
| Benzodiazepine receptor partial inverse agonist | AC-3933 | 1 phase II |
| Norepinephrine uptake inhibitor | Atomoxetine | 1 phase II/III |
| NMDA receptor channel blocker | Neramexane | 1 phase III |
| Monoamine uptake inhibitor | NS 2330 | 1 phase II |
| Adrenergic receptor antagonist | ORM-12741 | 1 phase II |
| Irreversible monoamine oxidase inhibitor | Rasagiline | 1 phase II |
| GABA(B) receptor antagonist | SGS742 | 1 phase II |
| Glutamate receptor modulator | LY451395 | 1 phase II |
| Anti-inflammatory | ||
| Non-steroidal anti-inflammatory drugs | Aspirin | 1 phase III |
| Indomethacin | 1 phase III | |
| Ibuprofen | 1 phase ? | |
| Nimesulide | 1 phase II | |
| Rofecoxib | 1 phase II/III, 1 phase ? | |
| Celecoxib | 1 phase III | |
| Lornoxicam | 1 phase II | |
| Unknown mechanism | Hydroxychloroquine | 1 phase III |
| Astrocyte activator | ONO-2506PO | 1 phase II |
| PYM50028 | 1 phase II | |
| Hormones and analogs | ||
| Antiprogestinic | Mifepristone | 3 phase II |
| Corticosteroid | Prednisone | 1 phase III |
| 11-β-hydroxysteroid dehydrogenase type 1 inhibitor | ABT-384 | 1 phase II |
| Gonadotropin-releasing hormone analog | Leuprolide acetate | 1 phase II |
| Estrogen receptor modulator | Raloxifene | 1 phase II |
| HRT | 5 phase ? | |
| Androgen receptor modulator | Dehydroepiandrosterone/testosterone | 2 phase ? |
| Growth hormone secretagogue | MK0677 | 1 phase II |
| Other or several mechanisms | ||
| c-kit (tyrosine kinase) inhibitor | Masitinib | 1 phase II, 1 phase III |
| Dimebon | 2 phase II, 5 phase III | |
| IFNβ-alpha 2a | 1 phase II | |
| IFNβ1a | 1 phase II | |
| N-acetylcysteine | 1 phase II | |
| Acetyl-L-carnitine | 1 phase ? | |
| Calcium antagonist | MEM 1003 | 1 phase II |
| Pleiotropic | ST101 | 2 phase II |
| Doxycycline and rifampin | 1 phase II, 1 phase III | |
| Cerebrolysin | 4 phase II, 1 phase III | |
| Somatostatin production enhancer | FK962 | 1 phase II |
| Unknown | VI-1121 | 1 phase II |
| Idebenone | 1 phase ?, 1 phase III | |
| Sodium oligo-mannurate | 1 phase II | |
| RO4601522 | 1 phase II | |
| T-817MA | 1 phase II | |
amechanism not fully elucidated