Review
Copyright ©The Author(s) 2015.
World J Neurol. Mar 28, 2015; 5(1): 5-16
Published online Mar 28, 2015. doi: 10.5316/wjn.v5.i1.5
Table 1 Known pathways affecting remyelination in multiple sclerosis
PathwayPotential protein targetsDrugsRef.
HyaluronanTLR2TLR2 Ab (OPN-305)[28]
HyaluronidaseVcpal[28,30]
Notch-1Notch-1(pan) BMS-906024[14,15,17,19]
Jagged-1-[14]
Endothelin-1PD142,893, sitaxentan, ambrisentan, atrasentan, BQ-123, zibotentan, bosentan, macitentan, tezosentan[17]
γ-secretaseMW167, LY450139[93]
Retinoid X receptorRXR-γBexarotene, IRX4204[31]
Wnt/ß-cateninß-cateninPKF118-744, CGP049090, PKF118-310, XTM000990, BC21, PKF115-584, PNU-74654[21,22]
Tankyrases 1-2XAV939, IWR1, JW74, JW55[57]
GSK3ßSB216763[20]
LINGO-1LINGO-1Anti-LINGO-1 Ab[23-25]
CXCL12/CXCR4CXCR7CCX771[37,38]
CXCR4AMD3100[37,38]
GPR17GPR17UnnamedOmeros
Table 2 Drug classes identified in remyelination screens
Drug classCompoundsRef.
Adrenergic agonistMethoxamine, nerepinephrine, tolaxoline, salmeterol[55]
Dopamine antagonistsOpipramol, flupentixol, fluphenazine, trifluoperazine, perphenazine, quetiapine[55,57]
Dopamine uptake inhibitor/dopamine agentsVanoxerine, GBR12935, methyldopa[55]
Histamine antagonistsClemastine, doxylamine, clemizole[55,57]
Adrenergic antagonistOpipramol, trifluoperazine, Cgp-26505, tolazoline, quetiapine[55,57]
Anticholinergics/cholinesterase reactivatorsHomatropine, clemastine, benztropine, disopyramide, trospium, diacetyl-monoxime, tiotropium, oxybutynin, atropine, ipratropium, hyosamine, atropine, methy atropine, octatropine, glycpyrrolate, carbetapentane, piperildolate, bevonium, propiverine, dicyclomine, mepenzolate, trihexylphenidyl[55,57]
Phosphodiesterase inhibitor8-bromo cyclic GMP, IBMX, enprofylline, enoximone, rolipram[55]
PPAR agonistGW-1929[55]
Ion channel blockersGabapentin, 8-aminobenzoic acid, disopyramide, oubain[55]
Serotonin modulatorsBrl-15572, paroxetine, clemizole, quetiapine[55,57]
Glutamate receptor antagonistUPF-523, l-aminodan-1,5-dicarboxylic acid[55]
Beta-catenin inhibitorXAV939[55]
Retinoic acid receptor agonistRetinoids, AM580[55,94]
Thyroid hormone receptor agonistT3[55,57]
COX-2 inhibitorsNiflumic acid, flunixin[55]
HMG-CoA reductase InhibitorMevastatin, simvastatin[55]
Rho kinase inhibitorMl-7, Ml-9, fasudil[55,63,94]
Antifungal/antibacterialKetoconazole[55]
Cathartic/emeticEmetine[55]
Opioid antagonistsLevallorphan[55]
GlucocorticoidsDexamethasone, hydrocortisone, budesonide, flunisolide[94]
EGF/ErbB2 inhibitorPD174265[94]
Table 3 Repurposed drug potential for remyelination
DrugSafetyBBBIn vitro effectsIn vivo effectsMS trialsMechanism
Quetiapine++++NCT02087631Atypical antipsychotic
Fasudil+NA++ROCK Inhibitor
Olesoxime++++NCT01808885Mitochondrial permeability transition pore modulator
Ibudilast++++NCT01982942 NCT01910259Phosphodiesterase PDE4 inhibitor
Simvastatin+++/-+/-NCT00647348HMG-CoA reductase inhibitor
Lovastatin++++HMG-CoA reductase inhibitor
Clemastine++++NCT02040298Antihistamine
IRX4204NA++NARetinoid X receptor agonist
Bexarotene+/-+--Retinoid X receptor agonist
Benztropine+/-+++M1/M3 muscarinic receptor antagonist