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Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide.

ABSTRACT: Melanocortin receptor agonists that bind to the melanocortin receptor 4 may cause increases in blood pressure (BP). Bremelanotide is an on-demand, subcutaneous melanocortin-receptor agonist that binds to the melanocortin receptor 4 and is being developed for the treatment of female sexual dysfunction.We studied the effects of bremelanotide administration on ambulatory BP and heart rate (HR), in a randomized, double-blind, placebo-controlled, and parallel-arm trial of three doses of bremelanotide (0.75, 1.25, and 1.75?mg) in 397 premenopausal women with female sexual dysfunction with normotension or controlled hypertension. Pharmacokinetic exposure was assessed in conjunction with ambulatory BP measurements.Increases in ambulatory SBP relative to placebo of 2.4 and 3.0?mmHg (1.25?mg; P values: 0.029 and 0.076) and 3.1 and 3.2?mmHg (1.75?mg; P values: 0.006 and 0.027), respectively, occurred following two doses, separated by 24?h at the 0 to 4-h postdose interval; peak increases typically lasted less than 15?min. Similar increases in the DBP were observed. Increases in BP were accompanied by reductions in HR during the 0-4-h interval for the 1.75-mg dose (-4.6 to -4.7?bpm; P?

SUBMITTER: White WB

PROVIDER: S-EPMC5338879 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide.

White William B WB Myers Martin G MG Jordan Robert R Lucas Johna J

Journal of hypertension 20170401 4

<h4>Background</h4>Melanocortin receptor agonists that bind to the melanocortin receptor 4 may cause increases in blood pressure (BP). Bremelanotide is an on-demand, subcutaneous melanocortin-receptor agonist that binds to the melanocortin receptor 4 and is being developed for the treatment of female sexual dysfunction.<h4>Methods</h4>We studied the effects of bremelanotide administration on ambulatory BP and heart rate (HR), in a randomized, double-blind, placebo-controlled, and parallel-arm tr ...[more]

PMID: 27977473

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Project description:To detect vascular variability anomalies (VVAs), a blood pressure and heart rate profile around the clock for at least 7 days is a start. As a minimum, measurement every 60 or preferably 30 minutes for a week is needed, to be continued if abnormality is found, to assess the about 24-hour (circadian) variability that exists in all individuals. As a first dividend, one then also obtains a glimpse of 2 of the very many longer-than-circadian periodicities, the biological half-week and week. Certainly if we can have sensors and computer chips in our cars that continuously monitor the pressure over a tire's life, we should be able to do the same job for ourselves for diagnostic and therapeutic decisions. Healthcare today emphasizes wellness with recommendations for exercise and a proper diet, yet these evaluations may not be adequate. BP may be measured at a visit to the doctor or before an exercise session, along with measuring body weight and performing a physical exam. The seeds of disease are planted long before they are visible, and what appears to be normal from a conventional point of view may in fact actually be abnormal. Hidden alterations of physiological function, masked by the body's remarkable adaptive capabilities, may become visible through a new diagnostic and therapeutic realm-chronobiology-that reveals hitherto unseen abnormalities. The tools of chronobiology may yield additional dividends, such as the detection of physiological "loads" related to stress and stress relief and the undesirable effcts of space weather upon personal events such as sudden cardiac death, societal events like terrorism and war, and natural disasters. Chronobiologi cally interpreted automatic ambulatory BP and heart rate (HR) monitoring (C-ABPM) may detect the antecedents of these types of events. C-ABPM is of interest in preventive cardiology, since it reveals new diagnoses as vascular variability anomalies (VVAs) and renders previous conventional diagnoses more reliable, such as that of an elevated BP. These VVAs include MESOR (midline-estimating statistic of rhythm)-hypertension, an elevation of the MESOR, which is diagnosed, like all other VVAs, only after I or preferably several replications of 7-day around-the-clock BP monitoring with available, affordable, and unobtrusive instrumentation. The recommendation for continuous C-ABPM recognizes several principles that constitute inseparably intertwined contributors to severe cardio-, cerebro- and renovascular diease. C-ABPM gauges wear and tear of genetics, physical loads, and in particular mental stress placed upon individuals from "womb to tomb" by daily life, including weather in extraterrestrial space as well as that on earth, as a continuous surveillance paradigm preventing us from flying blind to a change from less than 5% to near 100% in the risk of a stroke within 6 years.

Dataset Information

Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide.

Publications

Usefulness of ambulatory blood pressure monitoring to assess the melanocortin receptor agonist bremelanotide.

Similar Datasets

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