Dopamine D2 receptor agonists represent a first line treatment option in young patients with signs and symptoms of idiopathic Parkinson’s disease. An association between the use of D2 receptor agonists in Parkinson’s disease patients and heart failure has been reported. The identification of the underlying mechanism is needed to minimize the resultant cardiovascular morbidity. In a phase I clinical trial, a D2 receptor agonist (pramipexole) was administered to 52 healthy male subjects following a dose escalation scheme. Serial measurements of resting blood pressure, heart rate, and derived parameters including pulse pressure, pulsatile stress, and rate pressure product were analysed. Statistically significant and clinically relevant increases in most of the assessed parameters were found. Ten subjects were removed prematurely from the trial because of clinically significant increases in blood pressure and/or heart rate requiring immediate intervention with IV rescue medications including a selective β-1 blocker. The observed drug-related changes in vital signs were of clinical relevance and might explain some of the cardiovascular morbidity reported in patients receiving D2 receptor agonist in clinical settings. We suggest that the additional use of a β-1 blocking agent might mitigate the risk of cardiovascular morbidity among patients receiving long-term D2 receptor agonists. 1. Introduction Dopamine (D) is a naturally occurring catecholamine neurotransmitter that mediates its biologic functions by 2 main classes of G protein-coupled receptors: D1-class which includes D1 and D5 receptor (R) subtypes and D2-class which includes D2, D3, and D4 receptor subtypes [1, 2]. It has been reported that nigral and striatal D2Rs have a key function in controlling locomotor behaviour and motor skills [1–3] and that ablation of striatal D2Rs leads to Parkinsonian-like locomotor behaviour [4–6]. This substantiates the use of D2R agonists in the treatment of Parkinson’s disease (PD). In this context, D2R agonists are first line treatment option in de novo and young PD patients with mild-to-moderate symptoms. D2R agonists are also used in combination with levodopa, the gold standard treatment for PD, to delay the development of disabling motor complications in advanced stages of the disease [6–8]. In addition, D2R agonists are not metabolised by oxidative pathways and therefore do not lead to cytotoxic free radical formation that cooccurs with levodopa administration [7]. Unfortunately, the use of D2R agonists might be associated with cardiovascular (CV) complications
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