From the Guidelines
Flexeril (cyclobenzaprine) works primarily as a centrally acting muscle relaxant by affecting the brainstem, specifically the reticular formation, to reduce tonic muscle activity and decrease muscle spasm. The exact mechanism of action of cyclobenzaprine is not fully understood, but it is believed to involve the reduction of muscle spasm by decreasing the activity of descending serotonergic neurons 1.
Key Mechanisms
- Reduces tonic muscle activity by decreasing the activity of descending serotonergic neurons
- Does not directly act on the neuromuscular junction or skeletal muscle
- Relieves muscle spasms through a central sedative effect by binding to 5-HT2 receptors and modulating norepinephrine activity
Clinical Use
- Typical dosing is 5-10 mg three times daily, with a maximum recommended dose of 30 mg per day
- Generally prescribed for short-term use (2-3 weeks) as adjunctive therapy alongside rest and physical therapy for acute musculoskeletal conditions
- May cause sedation in many users and can impair driving and operation of machinery
- Prolonged use may lead to dependence and diminishing returns, as evidenced by the lack of sufficient evidence for its efficacy in chronic low back pain 1.
From the FDA Drug Label
Cyclobenzaprine HCl relieves skeletal muscle spasm of local origin without interfering with muscle function. It is ineffective in muscle spasm due to central nervous system disease. Cyclobenzaprine reduced or abolished skeletal muscle hyperactivity in several animal models Animal studies indicate that cyclobenzaprine does not act at the neuromuscular junction or directly on skeletal muscle. Such studies show that cyclobenzaprine acts primarily within the central nervous system at brain stem as opposed to spinal cord levels, although its action on the latter may contribute to its overall skeletal muscle relaxant activity Evidence suggests that the net effect of cyclobenzaprine is a reduction of tonic somatic motor activity, influencing both gamma (γ) and alpha (α) motor systems The mechanism of action of Flexeril (Cyclobenzaprine) is a reduction of tonic somatic motor activity, influencing both gamma (γ) and alpha (α) motor systems. It acts primarily within the central nervous system at brain stem levels. 2
From the Research
Mechanism of Action of Flexeril (Cyclobenzaprine)
- The mechanism of action of cyclobenzaprine is not fully understood, but it is thought to influence the α and γ motor neurons in the central nervous system, leading to the attenuation of muscle spasm 3.
- Cyclobenzaprine is believed to mediate its effects centrally via inhibition of tonic somatic motor function, likely through modulation of noradrenergic and serotonergic systems 4.
- Recent studies have shown that cyclobenzaprine exhibits low nanomolar affinity for the cloned human H1R, as well as that expressed in both rat and mouse brain, and binds to the H1R in a noncompetitive manner 4.
- Cyclobenzaprine's muscle relaxant effects are thought to occur centrally, and its ability to cross the blood-brain barrier suggests that off-target central antagonism of H1R by cyclobenzaprine may facilitate the significant sedative effect of this agent seen in patients 4.
Key Findings
- Cyclobenzaprine has been shown to be effective in relieving muscle spasm, reducing local pain and tenderness, and increasing range of motion in acute, painful musculoskeletal conditions 5, 6.
- The drug has a rapid onset of action, with significant improvements in symptoms reported within 3-4 days of treatment 5, 6.
- Cyclobenzaprine is generally well-tolerated, with somnolence and dry mouth being the most common adverse effects 5, 6.
- The drug's sedative effects are thought to be related to its ability to antagonize histamine H1 receptors in the central nervous system 4.