BioMed Research International / 2014 / Article / Tab 2

Review Article

Potential Therapeutic Strategies for Alzheimer’s Disease Targeting or Beyond β-Amyloid: Insights from Clinical Trials

Table 2

RCTs targeting neurotransmitter systems in recent years.

MechanismRCTStatusEstimated endDementia stageEnrollmentDurationReported outcomesDetails of drugs/RCTS

Cholinergic agents
 AchE inhibitorHuperzine APhase 2/3; completed2012.6Mild-to-moderate3906 months↑cognitive function, daily living activity, global clinical assessmentA natural AChEI; antioxidant and neuroprotective properties [215]
Ladostigil hemitartratePhase 2; ongoing2016.9MCI20036 monthsAntioxidant properties; modulates APP processing
 Nicotinic receptor  agonistEVP-6124Phase 3; ongoing2017.7Mild-to-moderate79026 weeksPositive outcomes in a 24-week phase 2b RCT
RO5313534Phase 2; completed2010.11Mild-to-moderate3896 monthsα7 nicotinic receptor agonist; as add-on therapy to donepezil
Ispronicline (AZD3480)Phase 2; ongoing2014.7Mild-to-moderate3001 yearα4β2 and α2β2 nicotinic receptor agonist
MT-4666Phase 2; ongoing2015.5Mild-to-moderate45024 weeks
ABT-089Phase 2; terminated2013.10Mild-to-moderate43424 weeks
MK-7622Phase 2b; ongoing2017.8Mild-to-moderate83012–24 weeksAs adjunctive therapy to donepezilα7 receptor modulator

Glutamatergic agentsAVP-923Phase 2; ongoing2014.9Mild-to-moderate20010 weeksBehavioral problemsNMDA receptor antagonist

Serotoninergic agentsLu AE58054Phase 3; ongoing*2016.1Mild-to-moderate≈2500Positive results in a phase 2 RCT, 278 participants, 6 months;Several phase3 RCTS with donepezil (AchEI);
SB-742457Phase 2; completed2011.8Mild-to-moderate6846 monthsshowed positive results

RCT: randomized controlled trial; AChEI: acetylcholinesterase inhibitor; MCI: mild cognitive impairment; NMDA: N-methyl-D-aspartic acid.
Data sources:
*RCTs with a combination of another drug.