Pramipexole as a possible cause of the syndrome of inappropriate antidiuresis

A 60-year-old man with Parkinson’s disease developed hyponatraemia with low plasma osmolarity, urine hyperosmolarity and an elevated urine sodium concentration. Plasma vasopressin (AVP) level was five times the upper normal limit and a diagnosis of the syndrome of inappropriate antidiuresis (SIAD) was made. Although the patient was treated with levodopa/carbidopa 500 mg/50 mg, entacapone 400 mg, seregiline 5 mg, cabergoline 1 mg, pergolide 250 μg and pramipexole 3 mg, SIAD resolved after the dose reduction of pramipexole. Dopamine is reported to facilitate AVP secretion through activation of D4 receptors. The hD4:hD2L pKi ratio calculated from published data is 0.017 for cabergoline, 0.44 for pergolide, 1.1 for ropinirole and 13 for pramipexole. The hD4:hD2 pKi ratio of dopamine is reported to be 1. Accordingly, pramipexole has a higher selectivity for D4 receptor than other dopamine agonists. Pramipexole is likely to increase AVP secretion, which is a prerequisite for developing SIAD.