New treatment for drop in blood pressure trialled by Imperial scientists

New treatment is evaluated for orthostatic hypotension, the drop in blood pressure some people experience when they stand up - News

By Laura Gallagher
Tuesday 23 October 2007

A new treatment for orthostatic or postural hypotension, the drop in blood pressure that some people experience when they stand upright, has been evaluated in a trial by scientists from Imperial College.

Orthostatic hypotension can occur in many conditions, particularly those where the autonomic nervous system - the part of the nervous system which controls bodily functions that are not consciously directed - is not working properly, such as Parkinson's disease. When a person stands up, the nerves that go to the heart and blood vessels cannot regulate blood pressure effectively enough to keep blood flowing normally around the body and to vital organs such as the brain.

Orthostatic hypotension has many symptoms. When people are upright, reduced blood flow to the brain can cause dizziness, light-headedness and problems with vision. In some cases orthostatic hypotension becomes debilitating. When the drop in blood pressure is pronounced, it can cause people to faint or fall and thus injure themselves, sometimes seriously, with the risk of fractures increasing in older patients.

In orthostatic hypotension that is caused by failure of the autonomic nervous system, the sympathetic nerves are unable to send the right signals to the blood vessels. This can be either because pathways in the brain are disrupted, or because the nerves to the blood vessels and heart are damaged. This results in an inability to secrete noradrenaline, the key neurotransmitter for sympathetic nerve endings. Noradrenaline acts on blood vessels to raise blood pressure.

The new drug effectively replaces reduced levels of the neurotransmitter with noradrenaline. Previously, noradrenaline had to be administered via injection or a pump as it was inactivated in the gut when swallowed. The new drug can be given orally, because it is a prodrug, meaning that it is administered in a less active form and is metabolised in the body into an active compound. Once the new drug is inside the body, it is acted upon by an enzyme known as dopa decarboxylase, which converts it directly into noradrenaline.

The trial found that the new drug raised noradrenaline levels and reduced the fall in blood pressure. The beneficial effects were seen with the first dose and persisted over the study period, and the drug was found to be well tolerated and safe.

The Imperial trial is the first in Europe that has used replacement of the natural neurotransmitter in these conditions. The drug was trialled in 121 patients with symptomatic orthostatic hypotension due to either Parkinson's disease or to multiple system atrophy, an allied disorder which results in autonomic failure. The study was performed across thirty European centres.

Other treatments for orthostatic hypotension include those that mimic the action of noradrenaline rather than replacing it, making them less effective than the new drug. Many also have adverse side effects.

Professor Christopher Mathias, Principal Investigator on the study from Division of Neuroscience and Mental Health at Imperial, said: "Orthostatic hypotension is a widespread and often under-recognised problem in many neurological and medical diseases. When caused by damage to the autonomic nervous system it is difficult to treat. This treatment has been effective in reducing troublesome orthostatic hypotension, and was well tolerated in the neurological disorders we studied. In due course it may be applicable to many other disorders where orthostatic hypotension occurs, including common diseases such as diabetes mellitus."

Professor Mathias presented the results of the study this month in Vienna at the Joint Meeting of the European Federation of Autonomic Societies and the American Autonomic Society.

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