Extracardiac uses of ranolazine

1. Neuropathic pain

Blocks late Na⁺ current in neurons

Reduces neuronal hyperexcitability

Studied in diabetic neuropathy and chronic pain syndromes

2. Myotonia (off-label)

Decreases skeletal muscle membrane excitability

Helpful in myotonic disorders when mexiletine is not tolerated

3. Skeletal muscle cramps

Reduces repetitive muscle fiber firing

Anecdotal benefit in chronic painful cramps

4. Glycemic control (metabolic effect)

Improves insulin sensitivity

Lowers HbA1c in patients with diabetes (observed in trials)

Mechanism: altered cellular Na⁺/Ca²⁺ handling and metabolism

5. Pulmonary hypertension (investigational)

Improves right ventricular diastolic function

May reduce pulmonary vascular remodeling via Na⁺/Ca²⁺ modulation

6. Neuroprotection (experimental)

Late Na⁺ current inhibition may reduce neuronal calcium overload

Studied in ischemia-related neuronal injury (preclinical data)

Key concept Ranolazine’s late sodium current (INa-late) inhibition explains its benefits beyond angina—particularly in neuromuscular, metabolic, and neuropathic conditions.

Clinical note Most extracardiac uses are off-label and supported by limited or emerging evidence; patient selection and QT monitoring remain important.

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