Mechanism of Action Comparison: Flexeril vs Baclofen

Introduction to Mechanisms

The American Geriatrics Society notes that 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 is essentially identical to the tricyclic antidepressant amitriptyline and does not directly relax skeletal muscle despite being marketed as a "muscle relaxant" 1
The American Geriatrics Society recommends that cyclobenzaprine and other so-called muscle relaxants have no evidence of efficacy in chronic pain and should not be prescribed believing they relieve muscle spasm 2
The drug's effects are nonspecific and not related to actual muscle relaxation, and it may inhibit polysynaptic myogenic reflexes in animal models, but whether this relates to pain relief in humans remains unknown 1

Baclofen is a GABA-B receptor agonist that works through a completely different mechanism than cyclobenzaprine 3, 1
Baclofen is classified as a centrally acting spasmolytic agent with documented spinal action, acting at the spinal level to suppress the excitability of spinal pathways to muscle motoneurons 4, 5

The American Geriatrics Society suggests that if true muscle spasm is suspected, baclofen is the appropriate choice rather than cyclobenzaprine or other "muscle relaxants" that lack specific antispasmodic mechanisms 1
The Mayo Clinic recommends that baclofen should be continued perioperatively due to risk of serious withdrawal symptoms including hallucinations, seizures, and potentially life-threatening complications with abrupt discontinuation 5
Both agents increase sedation risk when combined with opioids or CNS depressants, but through different mechanisms, with cyclobenzaprine through anticholinergic/tricyclic effects and baclofen through GABA-B agonism 5, 1