Table 1.

Summary of the receptor profile and functional actions of aripiprazole. In this table we have listed the affinity of aripiprazole to a wide range of relevant central nervous system receptors

Receptor type	Affinity (Ki)	Typology	Biological action vs agonist	Experimental system	Cells/tissues expressing target receptors	References
Dopamine
D1	−	Rat			CHO cells	Lawler et al. [45]
	−	Human				Shapiro et al. [36]
D2	++	Rat			Rat striatum	Lawler et al. [45]
	+++	Rat (D2S)	Antagonism	Inhibition of forskolin-induced cAMP production	CHO
	+++	Rat (D2L)			CHO
	++	Rat (D2L)	Partial agonism	Isoproterenol stimulation of cAMP accumulation	C6 glioma
	+++	Human	Antagonism	Quinpirole-induced GTPase activity	Rat brain striatal membranes	Inoue et al. [130]
			Partial agonism	Inhibition of forskolin-induced cAMP production	CHO	Burris et al. [37]
			Antagonism	Modulation of GIRK currents	MES-23.5	Shapiro et al. [36]
			Antagonism	GTPγS binding	CHO
			Partial agonism	Inhibition of forskolin-induced prolactin release	GFH4C1	Aihara et al. [208]
				Inhibition of forskolin-induced cAMP production
			Partial agonism	Inhibition of forskolin-induced cAMP production	CHO	Tadori et al. [209]
			Partial agonism	Inhibition of dopamine-induced ERK phosphorylation	CHO	Bruins Slot et al. [210]
			Partial agonism	D2-mediated MAPK phosphorylation	CHO	Urban et al. [42]
				D2-mediated potentiation of acid arachidonic release
			Agonism	Inhibition of forskolin-induced cAMP production	CHO (low-density hD2SRs)	Tadori et al. [40]
			Partial agonism		CHO (high-density hD2SRs)
			Antagonism		CHO (low-density hD2LRs)
			Partial agonism		CHO (high-density hD2LRs)
D3	++	Rat				Lawler et al. [45]
	++	Rat			C6 glioma
	++	Human	Partial agonism	Inhibition of forskolin-induced cAMP production	CHO	Tadori et al. [211]
			Partial agonism	Inhibition of forskolin-induced cAMP production	CHO	Tadori et al. [40]
D4	+/−	Rat			CHO	Lawler et al. [45]
	+/−	Rat	Partial agonism	Modulation of GIRK currents	Xenopus laevis oocytes	Newmann-Tancredi et al. [212]
D5	−	Rat			CHO	Lawler et al. [45]
	−	Human				Shapiro et al. [36]
DAT	−	Human
Serotonin
5-HT1A	++	Human	Partial agonism	Inhibition of forskolin-induced cAMP production	CHO	Shapiro et al. [36]
			Partial agonism	GTPγS binding	CHO	Jordan et al. [56]
			Partial agonism	GTPγS binding	Rat hippocampal membranes	Stark et al. [57]
			Agonism	Firing rate	5-HT dorsal raphe nuclei	Stark et al. [57]
5-HT1B	+/−	Human				Shapiro et al. [36]
5-HT1D	+	Human				Shapiro et al. [36]
5-HT1E	−	Human				Shapiro et al. [36]
5-HT2A	++	Human	Partial agonism	Stimulation of PI hydrolysis	C6-glioma cells expressing endogenous 5-HT2ARs	Shapiro et al. [36]
					GF62
5-HT2B	+++	Human	Inverse agonism	Stimulation of PI hydrolysis	HEK-293	Shapiro et al. [36]
5-HT2C	+	Human	Partial agonism	Stimulation of PI hydrolysis	PO1C	Shapiro et al. [36]
			Agonism	Stimulation of PI hydrolysis	COS-7
5-HT3	+/−	Rat				Shapiro et al. [36]
5-HT5A	−	Human				Shapiro et al. [36]
5-HT6	+/−	Rat			HEK-293	Lawler et al. [45]
	+/−	Human	Antagonism	Stimulation of cAMP production	HEK-293	Shapiro et al. [36]
5-HT7	+	Rat			HEK-293	Lawler et al. [45]
	++	Human	Partial agonism	Stimulation of cAMP production	HEK-293	Shapiro et al. [36]
SERT	−	Human				Shapiro et al. [36]
Noradrenaline
α1A	+	Human	Antagonism			Shapiro et al. [36]
α1B	+	Human	Antagonism
α2A	+	Human	Antagonism
α2B	+/−	Human
α2C	+	Human	Antagonism
β1	+/−	Human
β2	+/−	Human
NET	−	Human
Histamine
H1	+	Human	Antagonism			Shapiro et al. [36]
H2	−	Human
H3	+/−	Guinea pig
H4	−	Human
Acetylcholine
M1	−	Human				Shapiro et al. [36]
M2	−	Human
M3	−	Human
M4	−	Human
M5	−	Human
GABA
GABA-A	−	Rat				Shapiro et al. [36]
GABA-B	−	Rat
Glutamate
NMDA	−	Rat				Shapiro et al. [36]
Opiate
κ	−	Human				Shapiro et al. [36]
µ	−	Human
δ	−	Human

Where available, the results of functional studies to evaluate aripiprazole intrinsic activity on target receptors compared with the agonist are reported

cAMP cyclic adenosine monophosphate, CHO Chinese hamster ovaries, GIRK G-protein-coupled inward rectifier K⁺, GTP gamma-triphosphate, hD2LR human D2 long receptor, hD2SR human D2 short receptor, HEK human embryonic kidney, MAPK mitogen-activated protein kinase, +++ indicates ≤1—very high affinity, ++ indicates ≤10—high affinity, + indicates ≤100—moderate affinity, +/− indicates ≤1000—limited affinity, − indicates >1000—negligible affinity