Table 2.
Neuroprotective and regenerative effects of small-molecule receptor agonists and antagonists reported in two or more separate articles.
| Outcome | Benztropine* | Clemastine fumarate* | Clobetasol* | Diaryl-propionitrile | Dimethyl fumarate* | Fingolimod* (FTY720) | Indazole chloride | Laquinimod |
|---|---|---|---|---|---|---|---|---|
| Increased viability of OPC and/or OLG | ✓ | ✓ | ✓✓✓ | ✓ | ✓✓ | |||
| Preserved quantity, function, or integrity of neurons/axons | ✓ | ✓ | ✓ | ✓ | ✓✓✓✓ | ✓✓ | ✓✓ | |
| Protected against myelin loss and/or atrophy and lesions | ✓ | ✓✓ | ✓ | ✓ | ✓✓✓✓✓ | ✓ | ✓✓ | |
| Reduced CNS oxidative stress, apoptosis, or cellular dysfunction | ✓✓ | |||||||
| Stimulated production of neurotrophins and growth factors | ✓ | ✓ | ||||||
| Suppressed inflammatory microglial and/or astrocyte activation | ✓ | ✓✓ | ✓ | ✓✓ | ||||
| Promoted NPC/OPC proliferation or differentiation | ✓ | ✓ | ✓ | ✓ | ✓✓✓✓ | ✓ | ||
| Induced migration and recruitment of NPC/OPC | ✓✓ | |||||||
| Induced formation of new myelin | ✓ | ✓ | ✓✓ | ✓✓✓ | ✓✓ | |||
| Improved neurological function (physical or cognitive) | ✓✓ | ✓ | ✓ | ✓ | ✓✓ | ✓✓✓ | ✓ | |
| Relevant miscellaneous effect | Reduced brain S1PR1 expression | |||||||
| Animal models/clinical studies | Cuprizone and EAE | Phase II trial and LPC | LPC, EAE, and NMO | Cuprizone and EAE | Cuprizone | Cuprizone, EAE, LPC, JHMV, PTZ seizure, and human observational | Cuprizone and EAE | Cuprizone |
EAE: experimental autoimmune encephalomyelitis; JHMV: JHM strain of mouse hepatitis virus; LPC: lysophosphatidylcholine; NMO: neuromyelitis optica; NPC: neural precursor cell; OLG: oligodendrocyte; OPC: oligodendrocyte precursor cell; PTZ: pentylenetetrazole; S1PR1: sphingosine-1-phosphate receptor 1.
Each check (✓) represents an observed outcome from an individual study.
*
Indicates existing FDA or Health Canada approval.