Flexeril Generic Name
The generic name of Flexeril is cyclobenzaprine 1.
Drug Classification and Mechanism
Cyclobenzaprine is a tricyclic skeletal muscle relaxant that acts centrally within the brainstem to reduce tonic somatic motor activity 1. The drug relieves skeletal muscle spasm of local origin without interfering with muscle function, primarily by reducing both gamma (γ) and alpha (α) motor system activity 1.
Clinical Pharmacology
The mechanism involves:
- Central action at the brainstem level rather than the neuromuscular junction 1
- Noradrenergic modulation through activation of locus coeruleus neurons, leading to increased noradrenaline release in the ventral horn of the spinal cord 2
- Receptor antagonism including potent antagonism of histamine H1 receptors (which contributes to sedation), 5-HT2A receptors, and α1-adrenergic receptors 3, 4
Available Formulations
Cyclobenzaprine is available in multiple formulations:
- Immediate-release tablets: typically dosed 10 mg three times daily 1
- Extended-release capsules: 15 mg or 30 mg once daily 1
- Sublingual formulation (TNX-102 SL/Tonmya): approved in August 2025 specifically for fibromyalgia 5, 4
Important Clinical Considerations
Common adverse effects (≥3% incidence) include dry mouth, dizziness, fatigue, constipation, nausea, dyspepsia, and somnolence 1. The sedation is primarily mediated through off-target antagonism of central histamine H1 receptors 3.
Pregnancy warning: Cyclobenzaprine use during late pregnancy may induce ductal closure and persistent pulmonary hypertension in neonates through inhibition of prostaglandin and nitric oxide 6.
Pharmacokinetics: The drug has an elimination half-life of 32 hours (range 8-37 hours), with extensive hepatic metabolism via CYP3A4, 1A2, and 2D6 1. In elderly patients (>65 years), the half-life extends to 50 hours with 40% increased AUC 1.