What is the mechanism of action (MOA) of eperisone?

Mechanism of Action of Eperisone

Eperisone is a centrally-acting muscle relaxant that works through multiple mechanisms: inhibition of spinal mono- and multisynaptic reflexes, calcium channel antagonism in vascular smooth muscle, and suppression of sympathetic nerve activity to skeletal muscles, resulting in both muscle relaxation and improved blood flow without significant CNS sedation. 1, 2, 3

Primary Mechanisms

Spinal Reflex Inhibition

• Eperisone inhibits both mono- and multisynaptic reflexes in the spinal cord and supraspinal structures, which reduces abnormal muscle tone and contracture 1
• This central action distinguishes it from peripherally-acting muscle relaxants while avoiding the sedative effects typical of other centrally-acting agents 1

Calcium Channel Antagonism

• Eperisone acts as a calcium antagonist on vascular smooth muscle, blocking voltage-dependent calcium influx at the smooth muscle membrane 2
• The drug inhibits both the entry of extracellular calcium and the action of intracellular calcium on contractile proteins 2
• This calcium-blocking effect occurs at concentrations above 1 μM and reversibly blocks action potentials in vascular smooth muscle 2

Vascular Effects and Blood Flow Regulation

• Eperisone regulates blood supply to skeletal muscles through its vasodilatory properties, which is clinically significant because muscle contracture can compress small blood vessels and induce ischemia that releases nociceptive compounds 1
• The drug produces dose-dependent relaxation of arteries and veins previously contracted by various agents including norepinephrine, serotonin, acetylcholine, and potassium 4

Secondary Pharmacological Actions

Receptor Blockade

• Eperisone blocks multiple postjunctional receptors including alpha-1 and alpha-2 adrenergic, muscarinic, and serotonergic receptors 4
• The drug also blocks prejunctional alpha-2 adrenoceptors, which may contribute to its overall pharmacological profile 4

Sympathetic Nerve Modulation

• Eperisone exerts sympatho-suppressive effects on muscle sympathetic nerve activity (MSA) in resting skeletal muscles 3
• This sympathetic suppression is selective: the drug reduces MSA in resting muscles but does not affect MSA during active muscle contraction (such as standing or hand-gripping) 3
• The sympatho-suppressive effect may be related to drug-induced increases in blood flow to resting skeletal muscles and represents an additional mechanism for muscle relaxation 3

Clinical Implications

Distinguishing Features from Other Muscle Relaxants

• Unlike most skeletal muscle relaxants that cause significant CNS adverse effects (primarily sedation), eperisone is devoid of detrimental effects on the CNS 1
• This favorable CNS profile makes eperisone particularly useful when sedation must be avoided, contrasting with the American College of Physicians/American Pain Society guideline noting that other skeletal muscle relaxants are associated with central nervous system adverse effects 5

Pharmacokinetic Considerations

• Eperisone is rapidly absorbed (Tmax = 1.6 hours) and undergoes rapid elimination (half-life = 1.87 hours), which minimizes accumulation risk during repeated dosing 6
• The short half-life supports the typical dosing regimen of 50 mg every 8 hours without drug accumulation concerns 1, 6

Common Pitfalls and Caveats

• Do not confuse eperisone with FDA-approved skeletal muscle relaxants mentioned in guidelines (such as tizanidine, baclofen, or carisoprodol), as eperisone has a distinct mechanism combining central and peripheral actions 5, 1
• The vasodilatory mechanism means eperisone's efficacy extends beyond simple muscle relaxation to address ischemia-related pain in contracted muscles 1
• Minor gastrointestinal adverse reactions may occur (approximately 4% of patients), but CNS sedation is notably absent 1