Mechanism of Action Comparison: Flexeril vs Baclofen
No, Flexeril (cyclobenzaprine) and baclofen do not share the same primary mechanism of action—cyclobenzaprine is structurally identical to amitriptyline and acts through central anticholinergic and sedative effects without true muscle relaxation, while baclofen is a GABA-B receptor agonist that acts specifically at the spinal level to reduce neurotransmitter release and inhibit reflex arcs. 1
Cyclobenzaprine (Flexeril) Mechanism
Cyclobenzaprine is essentially identical to the tricyclic antidepressant amitriptyline and does not directly relax skeletal muscle despite being marketed as a "muscle relaxant." 1
The drug's effects are nonspecific and not related to actual muscle relaxation—it may inhibit polysynaptic myogenic reflexes in animal models, but whether this relates to pain relief in humans remains unknown. 1
Cyclobenzaprine and other so-called muscle relaxants (carisoprodol, chlorzoxazone, metaxalone, methocarbamol) have no evidence of efficacy in chronic pain and should not be prescribed believing they relieve muscle spasm. 1
These agents carry potential adverse effects similar to tricyclic antidepressants, including sedation, anticholinergic effects, and increased fall risk in older adults. 1
Baclofen Mechanism
Baclofen is a GABA-B receptor agonist that works through a completely different mechanism than cyclobenzaprine. 1
It activates GABA-B receptors located on primary afferent terminals, which retards calcium ion influx into nerve terminals and reduces the evoked release of excitatory amino acids and other neurotransmitters. 2
Baclofen is classified as a centrally acting spasmolytic agent with documented spinal action—it acts at the spinal level to suppress the excitability of spinal pathways to muscle motoneurons. 1
The drug has documented efficacy for spasticity from upper motor neuron syndromes (multiple sclerosis, spinal cord injury) through genuine reduction of velocity-dependent muscle tone. 3, 4
Clinical Implications
If true muscle spasm is suspected, baclofen is the appropriate choice rather than cyclobenzaprine or other "muscle relaxants" that lack specific antispasmodic mechanisms. 1
Baclofen should be continued perioperatively (including the day of surgery) due to risk of serious withdrawal symptoms including hallucinations, seizures, and potentially life-threatening complications with abrupt discontinuation. 1
Both agents increase sedation risk when combined with opioids or CNS depressants, but through different mechanisms—cyclobenzaprine through anticholinergic/tricyclic effects and baclofen through GABA-B agonism. 1
In older adults, baclofen carries higher fall risk than tizanidine (another alpha-2 agonist) but comparable risk to cyclobenzaprine, with baclofen causing more weakness as a side effect. 3, 5
Key Distinction
The fundamental difference is that baclofen has a specific, well-defined mechanism (GABA-B receptor agonism) with proven efficacy for true spasticity, while cyclobenzaprine is a tricyclic compound with nonspecific central effects that does not actually relax muscle. 1, 3, 2 They are grouped together as "muscle relaxants" by convention and FDA classification, but this categorization is misleading regarding their actual pharmacological actions.