Table 1.

Clemastine in central nervous system disorders.

Neurological disorder	Animal model	Doses and frequency	Major findings	Mechanisms	Ref.
Multiple sclerosis	EAE mouse model	10 mg/kg/d, oral, daily, for 32 days	Prevented axonal loss, accelerated remyelination, attenuated EAE clinical scores	CHRM1 inhibition	Mei et al. (2016)
	Lysolecithin-induced demyelination mice	10 mg/kg/d, gastric gavage, daily, for 14 days	Increase mature oligodendrocytes, accelerated remyelination, increased axon preservation	–	Jensen et al. (2018)
Amyotrophic lateral sclerosis	SOD1G93A mouse model	10 mg/kg/d, intraperitoneally injection, five times a week, from 40 days of age until end stage of the disease	Reduced microgliosis, modulates microglia-related inflammatory genes, enhances motor neuron survival	–	Apolloni et al. (2016b)
	SOD1G93A mouse model	50 mg/kg/d, intraperitoneally injection, five times a week, for 80 days or 125 days	Short term treatment decreased inflammation and SOD1 protein, enhanced autophagy, prolonged survival; long treatment produced opposite effects	mTOR signaling pathway	Apolloni et al. (2016a)
Aged	12-month-old mice	10 mg/kg/d, oral, daily, for 4 months	Enhanced myelination, preserved spatial memory capacity	CHRM1 inhibition	Wang et al. (2020)
Alzheimer's disease	APP/ PS1 mice	10 mg/kg/d, oral, daily, for 4 months	Decrease amyloid-β generation and accumulation, mitigated neuroinflammation, enhanced autophagy, rescued cognitive deficits	Reduced BACE1; Enhanced mTOR-mediated autophagy	Li et al. (2021)
	APP/ PS1 mice	10 mg/kg/d, oral, daily, for 2 months	Ameliorates accumulation of amyloid-β, prevented OPCs senescence, facilitated formation of myelin, rescued cognitive deficits	–	Xie et al. (2021)
	APP/ PS1 mice	10 mg/kg/d, oral, daily, for 3 months	Promoted new myelin formation, rescued cognitive decline	CHRM1 inhibition	Chen J. F. et al. (2021)
Perioperative neurocognitive disorders	Isoflurane anesthesia plus exploratory laparotomy induced mice	10 mg/kg/d, intraperitoneally injection, daily, for 2 weeks	Decreased neuroinflammation, promoted remyelination, improved survival of hippocampal neurons, ameliorated cognitive deficit	Blocked activation of WNT/β-catenin signaling pathway	Wu et al. (2021b)
Essential omega-3 fatty acids (n-3 PUFAs) deficiency related disorder	Dietary n-3 polyunsaturated fatty acids deficient mice	10 mg/kg/d, intraperitoneally injection, daily, for 7 days	Promoted oligodendrocytes maturation, rescued memory deficits in n-3 PUFA deficient animals	–	Madore et al. (2020)
Williams syndrome	Forebrain excitatory neuron-specific Gtf2i knockout mice	10 mg/kg/d, oral, daily, for 14 days	Restored myelination properties, increased axonal conductivity, rescued the behavioral deficits	–	Barak et al. (2019)
Autism spectrum disorder	Pitt-Hopkins syndrome mouse model	10 mg/kg/d, intraperitoneally injection, every 24 h for 14 consecutive days	Enhanced differentiation of OPCs, increased myelination activity, rescued electrophysiological deficits	–	Bohlen et al. (2023)
Inhaled anesthetics induced development disorder	Isoflurane induced developmental neurotoxicity in mie	10 mg/kg/d, oral, daily, for 14 days	Reverse cognitive dysfunction induced by isoflurane	Decreased activity of the mTOR signaling pathway	Li et al. (2019)
	Repeated sevoflurane exposure in neonatal mice	10 mg/kg/d, intraperitoneally injection, daily, for 26 days	Enhanced OLs maturation and myelination, alleviated cognitive impairment induced by sevoflurane	–	Zhang et al. (2022)
Normal brain development	C57BL/6 mice	50 mg/kg/d, intraperitoneally injection, daily, for 16 day	Increased oligodendrocyte differentiation, activated microglia	–	Palma et al. (2022)
Major depressive disorder	Socially isolated mice	10 mg/kg/d, oral, daily, for 2 weeks	Induced OPCs differentiation, enhanced myelination, reversed social avoidance behavior	Enhanced the activity of H3K9 histone methyltransferases	Liu et al. (2015)
	Socially defeated mice	10 mg/kg/d, oral, daily, for 5 days	Increased oligodendrogenesis, rescued the behavioral abnormalities	–	Shimizu et al. (2020)
	Chronic unpredictable mild stress induced mice	10 mg/kg/d, intraperitoneally injection, daily, for 5 days	Decreased pro-inflammatory cytokines, suppressed microglial M1-like activation	–	Su et al. (2018)
Schizophrenia	Cuprizone-induced mouse model of schizophrenia	10 mg/kg/d, oral, daily, for 5 days	Increased mature oligodendrocytes, rescued the schizophrenia-like behavioral changes	–	Li et al. (2015)
Hypoxic brain injury	Neonatal hypoxic mice injury model	10 mg/kg/d, oral, daily, for 7 days	Promoted OPCs differentiation, myelination, improved functional recovery	CHRM1 inhibition	Cree et al. (2018)
	Neonatal hypoxic mice injury model	10 mg/kg/d, oral, daily, for 8 days	Enhanced oligodendroglial differentiation, improved functional recovery	CHRM1 inhibition	Wang et al. (2018)
	Adult hypoxia exposure mouse	10 mg/kg/d, oral, daily, for 4 weeks	Increased the newly-formed myelin, prevented motor coordination deficits	–	Chen L. et al. (2021)
Hypoxic-ischemic brain injury	Bilateral common carotid artery ligation rat	1 mg/kg/d, intraperitoneally injection, daily, for 14 days	Reverse hypomyelination, restrain the upregulation of IL-1β	–	Xie et al. (2020)
Spinal cord injury	Spinal cord injury model of rat	10 mg/kg/d, oral, daily, for 28 days	Enhanced myelination, delayed axonal loss, improved functional recovery		Du et al. (2022)
	Spinal cord injury model of rat	10 mg/kg/d, oral, daily, for 7 or 14 days	Enhanced oligodendrocyte differentiation and myelin wrapping	Inhibited CHRM1 and then activated ERK1/2 pathway	Tong et al. (2022)
Remote fear memory	C57BL/6J mice	10 mg/kg/d, intraperitoneally injection	Induced new myelin formation, improved remote memory recall	–	Pan et al. (2020)
Remote memory consolidation	TrkB-deleted mice	10 mg/kg/d, intraperitoneally injection, daily, for 17 days	Promoted maturation of OPCs, improved remote memory recall	–	Hong et al. (2022)
Compression neuropathy	Mouse model of compression neuropathy	10 mg/kg/d, intraperitoneally injection, daily, for 2 weeks	Promoted myelin repair, improved electrophysiologic and histomorphometric changes	–	Lee et al. (2021)
Chemotherapy-induced cognitive impairment	Chemotherapy-induced cognitive impairment of mie	10 mg/kg/d, oral, daily, for 2 weeks	Enhanced oligodendrocyte differentiation, promoted remyelination, rescued cognitive function damage		Chen et al. (2022)
Intracerebral hemorrhage	Intracerebral hemorrhage mice	30 mg/kg/d, intraperitoneally injection, one time	Inhibited microglia-induced inflammatory and apoptosis, enhanced restoration of neuronal function	–	Zhi et al. (2021)