Clemastine fumarate
[CAS# 14976-57-9]

Identification

• Classification: API >> Antiallergic >> Antihistamine
• Name: Clemastine fumarate
• Synonyms: (2R)-2-[2-[(1R)-1-(4-Chlorophenyl)-1-phenylethoxy]ethyl]-1-methylpyrrolidine but-2-enedioic acid
• Molecular Formula: C₂₁H₂₆ClNO.C₄H₄O₄
• Molecular Weight: 459.97
• CAS Registry Number: 14976-57-9
• EC Number: 239-055-2
• SMILES: C[C@@](C1=CC=CC=C1)(C2=CC=C(C=C2)Cl)OCC[C@H]3CCCN3C.C(=C/C(=O)O)C(=O)O

Properties

• Solubility: 10 mM (water)

Safety Data

• Hazard Symbols: GHS06;GHS09 Danger
• Risk Statements: H301-H311-H331-H400-H410
• Safety Statements: P261-P262-P264-P270-P271-P273-P280-P301+P316-P302+P352-P304+P340-P316-P321-P330-P361+P364-P391-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Acute toxicity	Acute Tox.	3	H331
Acute toxicity	Acute Tox.	3	H301
Acute toxicity	Acute Tox.	3	H311

Discovery and Applications

Clemastine fumarate was discovered during the development of effective antihistamines in the mid-20th century. It is synthesized by reacting the active ingredient clemastine with fumaric acid to form the salt clemastine fumarate. The compound was found to have potent antihistamine effects and was therefore approved for clinical use.

Clemastine fumarate is a salt composed of clemastine, an ethanolamine derivative with antihistamine activity, and the dicarboxylic acid fumaric acid. Clemastine fumarate has the molecular formula C21H26ClNO · C4H4O4 and is typically a white to off-white crystalline powder. It is moderately soluble in water and soluble in ethanol and methanol. The compound is stable under normal conditions, but should be protected from light and moisture to prevent degradation.

Clemastine fumarate is a competitive antagonist of histamine H₁ receptors. By binding to these receptors, it inhibits the effects of histamine, a chemical mediator released during allergic reactions. This blockade reduces symptoms such as itching, sneezing, and nasal congestion associated with allergies.

Clemastine fumarate is used to relieve the symptoms of allergic rhinitis, including sneezing, runny nose, and nasal itching. It relieves symptoms by blocking histamine receptors in the nasal mucosa. It is effective in treating acute and chronic urticaria and reducing the severity of itching and rash associated with allergic skin reactions.

Clemastine fumarate has a mild antiemetic effect and is occasionally used to relieve nausea and vomiting caused by motion sickness.

Clemastine fumarate has been shown to have potential benefits in enhancing myelination and neural repair processes in the central nervous system, making it a subject of investigation for neurological diseases such as multiple sclerosis.

Veterinarians may prescribe clemastine fumarate to treat allergic dermatitis and pruritus in dogs and cats, which have allergic symptoms similar to those in humans.

Ongoing research is aimed at exploring new therapeutic uses and formulations of clemastine fumarate, including a role in treating autoimmune diseases and enhancing cognitive function through effects on neuroplasticity.

References

2024. Enhancing axonal myelination: Clemastine attenuates cognitive impairment in a rat model of diffuse traumatic brain injury. Translational Research: The Journal of Laboratory and Clinical Medicine, 270.
DOI: 10.1016/j.trsl.2024.01.008

2024. Neuroprotective Effect of Clemastine Improved Oligodendrocyte Proliferation through the MAPK/ERK Pathway in a Neonatal Hypoxia Ischemia Rat Model. International Journal of Molecular Sciences, 25(15).
DOI: 10.3390/ijms25158204

2024. Remyelination-oriented clemastine treatment attenuates neuropathies of optic nerve and retina in glaucoma. Glia, 72(8).
DOI: 10.1002/glia.24543