Clemastine

Clemastine (HS-592; Meclastine) is an orally active, blood-brain barrier-permeable H1 histamine receptor (H1 histamine receptor) antagonist with potent antiallergic effects. Clemastine also antagonizes muscarinic acetylcholine receptors (mAChR), particularly the M1 and M4 subtypes. In addition to antihistamine effects, Clemastine exhibits multiple pharmacological activities, especially in promoting central nervous system remyelination, activating autophagy and pyroptosis, exerting anti-apoptotic and neuroprotective effects, and suppressing inflammation^{[1][2][3][4][5][6]}. In Vitro:Clemastine (10 μM; 12 h) promotes Nrf2 nuclear translocation, activates the Nrf2/SQSTM1 pathway, and increases autophagy-related gene transcription in Hb-treated HT-22 cells^[1].
Clemastine (10-50 μM; 1 h for DARTS assay) directly binds to the M4 receptor, and M4 receptor signalling mediates clemastine-induced activation of the Nrf2/SQSTM1/TBK1 autophagy pathway in HT-22 cells^[1].
Clemastine (10 μg/mL; 3-18 h, 90 min) potentiates ATP-induced inflammasome activation and GSDMD-dependent pyroptotic cell death in LPS-primed THP-1 cells^[2].
Clemastine (10 μg/mL; 3-18 h) potentiates ATP-induced inflammasome activation and pyroptotic cell death in LPS-primed primary human monocyte-derived macrophages via a P2RX7-dependent mechanism^[2].
Clemastine (10 μg/mL; 18 h) induces lytic cell death in LPS-primed human iPSC-derived oligodendrocytes when combined with 2 mM ATP^[2].
Clemastine promotes oligodendrocyte precursor cell differentiation into mature myelinating oligodendrocytes via CHRM1 blockade and ERK pathway activation^[3].
Clemastine induces an NMDA receptor-rich state in oligodendrocyte precursor cells by modifying their membrane properties^[3].
Clemastine (1.25 μg/mL) reduces cellular apoptosis, improves mitochondrial structural damage, and promotes autophagy in LPS-stimulated H9c2 cardiomyocytes^[5]. In Vivo:Clemastine (1 mg/kg; i.p.; single administration) improves short-term neurological function, alleviates oxidative stress and neuronal death, and activates Nrf2/SQSTM1-mediated autophagy in mice with subarachnoid hemorrhage (SAH). These effects depend on the Nrf2 and mTOR signaling pathways^[1].
Clemastine (10 mg/kg; p.o.; once daily; for 28 consecutive days) reverses long-term cognitive impairment and attenuates hippocampal neuronal damage in a mouse model of subarachnoid hemorrhage (SAH)^[1].
Clemastine enhances remyelination and reverses behavioral changes in cuprizone-induced mouse models of multiple sclerosis^[2].
Clemastine accelerates remyelination, prevents axonal loss, and improves functional recovery in a mouse model of inflammatory demyelination-related multiple sclerosis^[2].
Clemastine enhances myelination in the prefrontal cortex and reverses behavioral alterations in socially isolated mice^[2].
Clemastine enhances myelination, delays axonal loss, and promotes functional recovery in mouse models of spinal cord injury^[2].
Clemastine preserves myelin integrity, reduces axonal loss, promotes oligodendrocyte differentiation, and improves motor function recovery in a rat model of spinal cord contusion injury^[4].
Clemastine promotes the differentiation of oligodendrocyte precursor cells and remyelination in a rat model of Pelizaeus-Merzbacher disease without immunosuppressive effects^[4].
Clemastine promotes remyelination in a lysophosphatidylcholine-induced demyelination mouse model^[4].
Clemastine (10-50 mg/kg; i.p.; single administration) increases the 7-day survival rate and reduces serum cTnI levels in CLP-induced septic rats; in addition, 30 mg/kg Clemastine improves cardiac function, alleviates cardiomyocyte apoptosis and mitochondrial damage, and promotes autophagy, with its anti-apoptotic effect dependent on autophagy activation^[5].
Clemastine (10 mg/kg; p.o.; once daily for 21 consecutive days) promotes oligodendrocyte precursor cell differentiation and remyelination, thereby improving the structural recovery and functional outcomes of the optic nerve and retina in a mouse model of glaucoma^[6].