Mechanism of Action
The mechanism of action for cyclobenzaprine is unclear. Studies from the 1980s in rats indicated cyclobenzaprine activates the locus ceruleus in the brain stem, leading to an increased release of norepinephrine in the ventral horn of the spinal cord, and the subsequent inhibitory action of norepinephrine on alpha motor neurons.
Cyclobenzaprine has been considered structurally related to the first-generation tricyclic antidepressants. Such tricyclics, including amitriptyline, act to inhibit the uptake of norepinephrine, resulting in increased transynaptic norepinephrine concentration. They have been shown to exert analgesic effects in chronic nerve and muscle pain. Cyclobenzaprine may have a similar effect.
Others contend the structure is more closely related to cyproheptadine, an antagonist at histamine H1 receptors, muscarinic acetylcholine receptors, and 5-HT2A serotonin receptors. Corroborating studies show cyclobenzaprine causes inhibition of descending serotonergic systems in the spinal cord by blocking 5-HT2A and 5-HT2C receptors. This action is thought to have an inhibitory effect on the alpha motor neurons in the ventral horn of the spinal cord, thereby resulting in decreased firing of alpha motor neurons and a reduction in spinal mono- and polysynaptic reflexes.
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