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Table 1 Drugs tested in the clinical trials included in the review and mechanisms of actions

From: Older patients are still under-represented in clinical trials of Alzheimer’s disease

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

  1. amechanism not fully elucidated