Rotigotine is a potent agonist at dopamine D1 receptors as well as at dopamine D2 and D3 receptors

Background and Purpose

Rotigotine acts as a dopamine receptor agonist with high affinity for the dopamine D₂, D₃, D₄ and D₅ receptors but with a low affinity for the dopamine D₁ receptor. We have investigated this further in radioligand binding and functional studies and compared the profile of rotigotine with that of other drugs used in the treatment of Parkinson''s disease (PD).

Experimental Approach

The binding of rotigotine to human dopamine D₁, D₂, D₃, D₄ and D₅ receptors was determined in radioligand binding studies using [³H]rotigotine and compared with that of standard antagonist radioligands. Functional interactions of rotigotine with human dopamine receptors was also determined.

Key Results

[³H]rotigotine can be used as an agonist radioligand to label all dopamine receptor subtypes and this can be important to derive agonist affinity estimates. Rotigotine maintains this high affinity in functional studies at all dopamine receptors especially D₁, D₂ and D₃ receptors and, to a lesser extent, D₄ and D₅ receptors. Rotigotine, like apomorphine but unlike ropinirole and pramipexole, was a potent agonist at all dopamine receptors.

Conclusions and Implications

Rotigotine is a high-potency agonist at human dopamine D₁, D₂ and D₃ receptors with a lower potency at D₄ and D₅ receptors. These studies differentiate rotigotine from conventional dopamine D₂ agonists, used in the treatment of PD, such as ropinirole and pramipexole which lack activity at the D₁ and D₅ receptors, but resembles that of apomorphine which has greater efficacy in PD than other dopamine agonists but has suboptimal pharmacokinetic properties.     

Diagnostic value of echocardiographic markers for diastolic dysfunction and heart failure with preserved ejection fraction

Heart Failure Reviews - This study aimed to evaluate the diagnostic performance of echocardiographic markers of heart failure with preserved ejection fraction (HFpEF) and left ventricular diastolic...     

Access to kidney transplantation. Has the United States eliminated income and racial differences?

We analyzed the effect of patient and dialysis unit characteristics on access to kidney transplantation using several different approaches, including an analysis of individual patient data from a systematic random sample of 2900 new dialysis patients from each year 1981 to 1985 (14721 patients total). Additional analyses focused on the composition of transplant waiting lists and aggregate data from a 1984 census of 1133 dialysis and transplant units. White, male, young, nondiabetic, high-income patients treated in smaller units are more likely to receive a cadaver transplant under Medicare than are other kidney patients. Profit status of the dialysis unit was not found to be correlated to access to transplantation, although size of the unit may be correlated to access. Future analysis should focus on whether patient access has been inappropriately compromised. Possible factors unexplored in this analysis include differential patient preferences and medical suitability, as well as differential medical access.     

Wound protectors mitigate superficial surgical site infections after pancreatoduodenectomy

Background

Whether the choice of antibiotic prophylaxis, the type of incision, or the use of wound protectors decreases surgical site infections (SSIs) in patients undergoing pancreatoduodenectomy (PD) remains unknown.

Hemodynamic effects of sildenafil in patients with stable ischemic heart disease

Background: Recently the new specific phosphodiesterase-5 inhibitor sildenafil was introduced into therapy for erectile dysfunction. The hemodynamic effects of sildenafil may be potentially hazardous for patients with cardiac disease. Sildenafil has been reported to augment the hypotensive effects of nitrates. There is sparse information regarding the systemic and pulmonary hemodynamic effects of a single oral dose of sildenafil in patients with stable angina. Methods: Male patients referred for coronary angiography with diagnosis of chronic stable angina were enrolled in this study to assess the acute hemodynamic effects of sildenafil. Patients receiving long-acting or sublingual nitrates for the last 6 h before the study were excluded. Hemodynamic measurement were taken during right and left heart catheterization in the basal state and 60 min after 50 mg of oral sildenafil. Results: Twelve patients (age 53±7 years) were studied. All had stable angina CCS class II or III. Four had previous myocardial infarction. By coronary angiography, seven patients had at least one coronary artery with >70% stenosis, four had at least one with 50–70% stenosis, and one had only intimal irregularities. There were no significant effects of sildenafil on systemic or pulmonary arterial pressure, left ventricle endiastolic pressure, cardiac output, and systemic or pulmonary vascular resistance (P>0.05 for all). No adverse events were observed. Conclusion: A single oral dose of sildenafil had no significant hemodynamic effect in supine patients with stable angina. Isolated administration of sildenafil does not appear to be associated to adverse cardiovascular effects.