Table 2.

Candidates and mechanism of action under development for the treatment of AD-related neuropsychiatric symptoms.

Candidate Drugs	Target	Mechanism of Action	Target NPS	Disease Stage of AD	Clinical Status	References
Lumateperone (Caplyta)	Neurotransmitter receptors	A 5-HT2A antagonist, a SERT inhibitor, a DRD2 antagonist, a GluN2B modulator	Depression			[78,79,80,81]
Psilocybin	Neurotransmitter receptors	A modulator of 5-HT1A, 5-HT2A, and 5-HT2C receptors		Prodormal/prodromal-mild	Phase 1	[82,83,84]
Cannabidiol	Neurotransmitter receptors	Cannabinoid, an agonist against 5-HT1A, A2A, and TRP-V1 receptors, anti-inflammatory action	Anxiety	Mild–moderate dementia, prodormal/prodromal-mild	Phase 1 Phase 2	[85,86]
Dextromethorphan	Neurotransmitter receptors	NMDA receptor antagonist; σ-1 receptor agonist, a SERT and NET inhibitor, a nicotinic σ3β4 receptor antagonist	Agitation			[15,75,76,77,87,88]
AVP-923 (Neudexta)	Neurotransmitter receptors	dextromethorphan/ quinidine		Mild–moderate dementia, severe dementia		[87,89,90]
AXS-05	Neurotransmitter receptors	dextromethorphan/ bupropion NMDA receptor antagonist; σ-1 receptor agonist. A SERT and NET inhibitor		Mild–moderate dementia, severe dementia	Phase 3	[91,92,93]
Nabilone	Cannabinoid receptor	A partial agonist against CB1 and CB2 receptor		Mild–moderate dementia, severe dementia	Phase 3	[94,95]
Brexpiprazole	Neurotransmitter receptors	A partial agonist against D2, D3 receptor, and 5-HT1A. A serotonin and dopamine modulator		Mild–moderate dementia, severe dementia		[42,96,97]
AVP-786	Neurotransmitter receptors	NMDA receptor antagonist; σ-1 receptor agonist. A SERT and NET inhibitor		Mild–moderate dementia, severe dementia	Phase 3	[16,98]
Dexmedetomidine	Neurotransmitter receptors	An α2 adrenergic agonist		Mild–moderate dementia, severe dementia	Phase 3	[99,100,101]
JZP541	Cannabinoid receptor	An agonist against CB1 and CB2 receptor		Mild–moderate dementia Severe dementia	Phase 2	[16]
Dronabinol	Cannabinoid receptor	A weak partial agonist against CB1 and CB2 receptor		Mild–moderate dementia	Phase 2	[102,103,104]
IGC-AD1	Cannabinoid receptor	Cannabinoid, a partial agonist against CB1 receptor		Mild–moderate dementia, severe dementia	Phase 2	[16,86]
Prazosin	Neurotransmitter receptors	An α1 adrenergic antagonist			Phase 2b	[105,106]
SCI-110	Neurotransmitter receptors	Tetrahydrocannabinol and palmitoylethanolamide		Mild–moderate dementia	Phase 2	[107,108]
THC-Free CBD	Cannabinoid receptor	An agonist against CB1 and CB2 receptor		Mild–moderate dementia, severe dementia	Phase 2	[109,110]
Masupirdine	Neurotransmitter receptors	A 5-HT6 receptor antagonist		Mild–moderate dementia	Phase 3	[111,112,113,114]
MK-8189	Phosphodiesterase	A PDE10a inhibitor		Mild–moderate dementia	phase 1	[115]
Pimvanserin	Neurotransmitter receptors	A selective inverse agonist of the serotonin 5-HT2A receptor	Psychosis		Phase 3	[47,116,117]
ACP-204	Neurotransmitter receptors	A potent and selective antagonist/inverse agonist of 5-HT2A receptor		Mild–moderate dementia, severe dementia	Phase 2 Phase 3	[15,16,83,118]
KarXT	Cholinergic modulator	A dual M1/M4 muscarinic acetylcholine receptor agonist		Mild–moderate dementia	Phase 3	[119,120,121,122,123]
Seltorexant	Orexin system	A selective antagonist of the orexin-2 receptor	Sleep disturbances	Mild–moderate dementia	Phase 2	[124,125]
SLV	Neurotransmitter receptors	A selective 5-HT6 receptor antagonist	Social processing			[126]
N-acetyl cysteine	Redox system	An antioxidant and glutathione inducer				[71]
BDNF	Neurotrophic factor	A member of the neurotrophin family, TrkB activation				[65,72,73]
Oxytocin	Endocrine system	a nonapeptide hormone, oxytocin receptor activation				[127,128,129]