Table 3.

Potential modulators of CaMKII and/or CaMKIV and their activity in animal tests/models of neuropsychiatric and neurodegenerative disorders.

Potential Modulator	Action	Animal Models/Tests	Reference
Antidepressant-Like Activity
KN-62	-inhibition of CaMKII -inhibition of GluA1 (Ser831) phosphorylation	FST, SPT, and ethanol withdrawal (in rats)	[126,141,142,143,144,146]
Paroxetine, venlafaxine, fluvoxamine (long treatment)	-activation of CaMKII in synaptic vesicles and synaptic cytosol -activation of CaMKIIα phosphorylation in hippocampus -activation of synaptotagmin phosphorylation	-	[127,130,131,132]
Fluoxetine (chronic)	-inhibition of CaMKII expression in nucleus accumbens -inhibition of ΔFosB binding to the CaMKIIα promoter -inhibition of lysine-9 histone H3 acetylation and activation its dimethylation at the CaMKIIα promoter in nucleus accumbens	chronic social defeat stress and SPT (in mice)	[128]
Fluoxetine, desipramine, Reboxetine (long treatment)	-inhibition of CaMKII -activation of Thr(286) phosphorylation	-	[129]
Imipramine (chronic)	-inhibition of CaMKIIβ (in lateral habenula or hippocampal soluble fraction) -inhibition of GluR1	congenitally learned helplessness (in rats)	[15,134]
Fluoxetine (chronic)	-inhibition of CaMKIIβ in hippocampus CA1 -inhibition of the p38 MAPK phosphorylation -inhibition of transcription factor 2 activating	FST and SPT during chronic unpredictable mild stress and LPS-induced model of depression (in rats)	[119]
Fluvoxamine, desipramine (chronic)	-activation of CaMKII in presynaptic vesicles of prefrontal /frontal cortex -activation of synaptotagmin phosphorylation	-	[10]
Desmethylimipramine (chronic)	-activation of CaMKII in hippocampal synaptic vesicle fraction	-	[133]
Ketamine	-activation of CaMKII -activation of GluA1 in the hippocampus	FST, TST, and NSFT (in mice)	[135]
Ketamine	-inhibition of CaMKIIα overexpression in hippocampus -inhibition of GluN2B phosphorylation in the hippocampus	OFT, FST, and NSFT during LPS-model of depression (in mice)	[136]
Sunifiram (chronic)	-activation of CaMKII phosphorylation in OB mice in the hippocampus CA1 -activation of glycine-bindind site of NMDAR	no effect in TST (in OB mice)	[120]
Nefiracetam (chronic)	-activation of CaMKII and CaMKIV phosphorylation in OB mice in the hippocampus CA1 as well as in amygdala and prefrontal cortex -activation of CREB phosphorylation in amygdala and prefrontal cortex	TST and FST (in OB mice)	[137]
SAK3 (ethyl 8’-methyl-2’,4-dioxo-2-(piperidin-1-yl)-2’H-spiro[cyclopentane-1,3’-imidazo[1,2-a]pyridine]-2-ene-3-carboxylate) (chronic)	-activation of CaMKII and CaMKIV phosphorylation in OB mice -activation of T-type calcium channel	TST, FST, and SPT (in OB mice)	[138]
Guanxin Danshen formula	-inhibition of CaMKII	FST, TST, and SPT during unpredictable chronic mild stress (in rats)	[139]
3,5,6,7,8,3,4′-Heptamethoxyflavone	-activation of p-CaMKII in the hippocampus	FST and TST during corticosterone-induced depression (in mice)	[140]
Baicalin	-inhibition of CaMKII	FST, TST, and SPT during mice chronic unpredictable stress (in mice)	[150]
Ursolid acid, creatine, ferulic acid, (octylseleno)-xylofuranoside, memantine and 7-fluoro-1,3-diphenylisoquinoline-1-amine	-activation of CaMKII	FST or TST (in mice)	[141,142,143,144,145,146,147,148,149]
Nicotine	-activation of CaMKIV -activation of α7-nAChRs	TST and FST (in CaMKIV knockout mice)	[43]
Fluoxetine (chronic)	-activation of CaMKIV	SPT and OFT during chronic unpredictable stress (in rats)	[174]
Anxiolytic-like activity
TatCN21peptide	-inhibition of CaMKII and αCaMKII -inhibition of NR2B phosphorylation	EPM and OFT (in rats)	[41]
Diazepam	-activation of p-CaMKII in the hippocampus and striatum -inhibition of MEK and ERK1/2	OFT and EPM (in mice)	[187]
Memantine	-inhibition of CaMKII phosphorylation -inhibition of ERK signalling	OFT and EPM during chronic alcohol exposure (in rats)	[188]
Genistein	-activation of p-CaMKII -activation of the serotonergic transmission in the amygdala	EPM and contextual freezing behavior during posttraumatic stress disorder (in rats)	[189]
Procognitive activity
Rivastigmine (chronic)	-activation of CaMKII and CaMKIV phosphorylation -activation of long-term potentiation in the hippocampus	Y-maze task, NOR, passive avoidance task, and Barnes maze task (in OB mice)	[222]
Sunifiram	-activation of CaMKII -activation of the glycine-binding site of NMDAR	Y-maze task, NOR (in OB mice)	[120]
Nefiracetam	-activation of CaMKII -activation of GluA1 phosphorylation -activation of long-term potentiation in rats	-	[221]
Naringin (chronic)	-activation of CaMKII phosphorylation -activation of AMPA phosphorylation -activation of long-term potentiation in mice model of Alzheimer’s disease	-	[224]
Genistein	-inhibition of CaMKIV in the hippocampus -inhibition of tau phosphorylation	special learning and memory in Morris water maze during Alzheimer ‘s disease model (in rats)	[235]

CaMKII—calcium/calmodulin-dependent kinase II, CaMKIV—calcium/calmodulin-dependent kinase IV, EPM—elevated plus maze test, FST—forced swim test, LPS—lipopolysaccharide, NOR—novel object recognition task, NSFT—novelty suppressed feeding test, OB mice—olfactory bulbectomized mice, OFT—open field test, p-CaMKII—phosphorylated-CaMKII, SPT—sucrose preference test, TST—tail suspension test.