Pramipexole as a possible cause of the syndrome of inappropriate antidiuresis

Abstract

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.

Syndrome of Inappropriate Antidiuretic Hormone Secretion Associated with Pramipexole in a Patient with Parkinson’s Disease

“…Recently, two cases with SIADH induced by pramipexole were reported. 7 , 10 In one case, SIADH developed during first two weeks of pramipexole therapy, 10 and in the other case, SIADH developed during dose escalation of pramipexole, 7 as with our patient.…”

Syndrome of Inappropriate Antidiuretic Hormone Secretion Associated with Pramipexole in a Patient with Parkinson’s Disease

“…Dopaminergic activation via D4 receptors reduces GABA release in the supraoptic nucleus, and then AVP release is facilitated 6. Pramipexole has a high affinity for the D2, D3 and D4 receptors 7,8. Therefore, a possible explanation for SIADH in this patient is the pramipexole-enhanced AVP secretion resulting from reducing GABA release through D4 receptors in the supraoptic neurons.…”

“… 6 Pramipexole has a high affinity for the D2, D3 and D4 receptors. 7 , 8 Therefore, a possible explanation for SIADH in this patient is the pramipexole-enhanced AVP secretion resulting from reducing GABA release through D4 receptors in the supraoptic neurons. Pramipexole has a higher selectivity for D4 receptor than other dopamine agonists.…”

“…Clinicians should consider medical derangement when a rapid aggravation of parkinsonian symptoms is developed in a patient with Parkinson’s disease. Recently, two cases with SIADH induced by pramipexole were reported 7,10. In one case, SIADH developed during first two weeks of pramipexole therapy,10 and in the other case, SIADH developed during dose escalation of pramipexole,7 as with our patient.…”

“…Arginine vasopressin (AVP) is induced by noradrenalin and serotonin through adrenergic α1 receptor and 5-HT2A/2C receptors in supraoptic nucleus. 6 , 7 AVP-secreting supraoptic neurons are under the control of prominent γ-amino butyric acid (GABA) inhibition, and D4 receptors are located on GABA terminals in the rat supraoptic nucleus. 6 Dopaminergic activation via D4 receptors reduces GABA release in the supraoptic nucleus, and then AVP release is facilitated.…”