What is the mechanism of action of Flavoxate?

Mechanism of Action of Flavoxate

Flavoxate primarily works by directly relaxing smooth muscle in the urinary tract through inhibition of L-type calcium channels, with minimal anticholinergic activity. 1, 2

Primary Mechanisms

• Direct smooth muscle relaxation:

  • Acts directly on urinary tract smooth muscle 1
  • Inhibits voltage-dependent L-type calcium channels in detrusor myocytes 2
  • Causes concentration-dependent reduction of K+-induced contractions in human urinary bladder 2

• Calcium channel modulation:

  • Inhibits the peak amplitude of voltage-dependent nifedipine-sensitive inward Ba²⁺ currents 2
  • Shifts the steady-state inactivation curve of Ba²⁺ currents to the left 2
  • Interacts with the α₁C subunit protein of human L-type Ca²⁺ channels (CaV1.2) in detrusor smooth muscle 2

Pharmacokinetic Properties

• Onset and peak effect:

  • Time to onset of action: approximately 55 minutes 1
  • Peak effect observed at approximately 112 minutes 1

• Elimination:

  • 57% of flavoxate HCl is excreted in the urine within 24 hours 1

Clinical Implications

• Flavoxate is primarily used for treating urinary urgency and urge incontinence 3, 4
• The drug's minimal anticholinergic effects distinguish it from other agents used for similar indications 5
• Effective dosages range from 600-1200 mg daily, with some evidence suggesting superior urodynamic outcomes at higher doses 4

Important Considerations

• Unlike many anticholinergic drugs used for overactive bladder, flavoxate's mechanism primarily involves calcium channel modulation rather than muscarinic receptor antagonism 5, 2
• The drug's calcium channel blocking effect (Ki = 10 μM) is the key mechanism behind its muscle relaxant properties 2
• Flavoxate's direct action on smooth muscle provides a mechanistic explanation for its clinical efficacy in treating urgency and urge incontinence 1, 3

This mechanism of action explains flavoxate's therapeutic effects in urinary disorders while accounting for its favorable side effect profile compared to agents with stronger anticholinergic properties.