Is Chlorzoxazone Anticholinergic?
No, chlorzoxazone is not an anticholinergic medication. Chlorzoxazone is a centrally acting skeletal muscle relaxant that works through modulation of small-conductance calcium-activated potassium (SK) channels in the brain, not through anticholinergic mechanisms. 1
Mechanism of Action
Chlorzoxazone acts as a centrally acting muscle relaxant by modulating recombinant small-conductance Ca²⁺-activated K⁺ channels (SK2 channels) in the brain, which affects neuronal excitability rather than blocking muscarinic receptors. 1
The drug is metabolized to 6-hydroxychlorzoxazone by cytochrome P450 2E1 (CYP2E1) and does not possess anticholinergic properties in its mechanism of action. 2, 3
Important Clinical Distinction
Chlorzoxazone should not be confused with cyclobenzaprine, which is a different muscle relaxant that does have significant anticholinergic effects:
Cyclobenzaprine acts as a centrally acting 5-HT₂ receptor antagonist and is structurally related to tricyclic antidepressants, producing significant anticholinergic adverse effects including hallucinations, confusion, drowsiness, constipation, urinary retention, and dry mouth. 4
The American Geriatrics Society identifies muscle relaxants including cyclobenzaprine as potentially inappropriate medications for older adults due to anticholinergic effects, sedation, and fall risk—but this classification applies to cyclobenzaprine specifically, not chlorzoxazone. 5, 6
Adverse Effects of Chlorzoxazone (Non-Anticholinergic)
While chlorzoxazone is not anticholinergic, it does carry significant risks:
Chronic use is associated with hepatotoxicity, central nervous system depression, and risk of abuse, and should be avoided for long-term use, especially in older adults. 5
Hepatotoxic reactions have been documented, including two deaths involving hepatic failure in a review of 23 cases since 1970. 7
The American Geriatrics Society's 2019 Beers Criteria strongly recommends avoiding muscle relaxants including chlorzoxazone in older adults due to high risk of adverse effects—but these are primarily CNS depression and sedation, not anticholinergic effects. 5
Clinical Implications
When deprescribing strongly anticholinergic medications in older adults, focus on older antihistamines such as diphenhydramine, muscle relaxants such as cyclobenzaprine (not chlorzoxazone), and overactive bladder agents such as oxybutynin. 8
If concerned about anticholinergic burden in a patient taking chlorzoxazone, the risk comes from other medications in the regimen, not from chlorzoxazone itself. 8