Old drugs have been around long enough to let thier problems show. The risks are much lower and side effects are known. And every now and then we stumble upon a new use. Called "off label" use, they don't have to pass the FDA labyrinth and their use is a matter between patient and doctor.


A story from April 17, 2006 deals with unsuspected protective and regenerative powers of an old blood pressure medication.


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A research team led by Riyi Shi (REE-yee SHEE) and Richard Borgens found that hydralazine, a medication that relaxes veins and arteries, may be an antidote for acrolein, a deadly toxin that is produced after a nerve cell is injured.

New findings based on research at the cellular level are detailed in two studies published in the Journal of Neuroscience Research today (Monday, April 17). In the first article, researchers examine how acrolein attacks and kills cells. In the second article, they demonstrate that cell death caused by acrolein (a-KRO-le-an), a byproduct of an injury, can be reversed when hydralazine is administered.

"This is probably the most important fundamental discovery we have made at the Center for Paralysis Research because we are saving nerve cells from death," said Borgens, Mari Hulman George Professor of Applied Neurology in the School of Veterinary Medicine and founder of the paralysis research center where the research was conducted.

"Initially we may use this discovery for spinal cord injury and stroke, but we can expect further studies will look at how it works against a whole spectrum of injury and disease," he said.


Purdue researchers collected data on acrolein from cell cultures and found that the potent toxin can destroy entire groups of cells in less than 12 hours. But they also determined that the cells would survive if the toxin were treated with hydralazine that acts very much like an antidote, Borgens said.

"We analyzed other natural toxins as well, and our success has been remarkable," Borgens said. "We found that more than 80 percent of the cells can be saved with hydralazine."

Acrolein stays in the body for days and is responsible for secondary damage that keeps injured cells from healing. The idea to use hydralazine against acrolein is a logical extension of research on the toxin, such as the use of a beta blocker against high blood pressure or chicken soup for a cold, Shi said.

"Acrolein is one of the causes of free radicals that are known to damage cells, so it makes sense to stop them from ever being produced," said Shi, who is associate professor of basic medical science in Purdue's School of Veterinary Medicine. "With hydralazine, we are attacking the root of the problem rather than the symptom."


Acrolein is a type of cell toxin called an aldehyde; and the drug, hydralazine, is effective because it has the ability to trap aldehydes and stick to them. Once hydralazine binds to the aldehyde, the toxin is neutralized, deactivated and secreted, Shi said.

The Purdue researchers started looking at alternative methods to save cells because other studies that had tried to use antioxidants to deactivate free radical molecules had failed in human clinical trials in traumatic brain injuries, strokes and spinal cord injuries.

"If we intervene early enough, we may have the ability to slow down the process of diseases, such as Alzheimer's and Parkinson's, which would be significant," Shi said. "If we can prevent these diseases from getting worse, we can give people a better quality of life."

Peishan Liu-Snyder, who graduated last summer and will be a post-doctoral fellow at Brown University in June, also was part of the Purdue research team. She became interested in research at the Center for Paralysis Research when it focused on the use of liquid polymers that prevent nerve cells from rupturing, enabling them to heal themselves.

"We found hydralazine works well after the initial injury period because it targets the secondary injury process," said Liu-Snyder. "It binds to the acrolein to inactivate its toxicity."
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Some things to note- 1) PD is purpotedly a constant cascade of dying cells, i.e. a slow rolling brain injury where one death triggers the next and 2) this drug works by causing the walls of blood vessels to relax and grow bigger - this allows more blood (and oxygen) to reach the brain.




1: J Neurosci Res. 2006 Jul;84(1):219-27.

Hydralazine rescues PC12 cells from acrolein-mediated death.

Liu-Snyder P, Borgens RB, Shi R.

Center for Paralysis Research, Department of Basic Medical Sciences, School of
Veterinary Medicine, Purdue University, West Lafayette, Indiana 47907-2096, USA.

Acrolein, a major lipid peroxidation product, has been associated with both CNS
trauma and neurodegenerative diseases. Because of its long half-life, acrolein
is a potent endogenous toxin capable of killing healthy cells during the
secondary injury process. Traditionally, attempts to intervene in the process of
progressive cell death after the primary injury have included scavenging
reactive oxygen species (so-called free radicals). The animal data supporting
such an approach have generally been positive, but all human clinical trials
attempting a similar outcome in human CNS injury have failed. New drugs that
might reduce toxicity by scavenging the products of lipid peroxidation present a
promising, and little investigated, therapeutic approach. Hydralazine, a
well-known treatment for hypertension, has been reported to react with acrolein,
forming hydrazone in cell-free systems. In the companion paper, we have
established an acrolein-mediated cell injury model using PC12 cells in vitro.
Here we test the hypothesis that the formation of hydrazone adducts with
acrolein is able to reduce acrolein toxicity and spare a significant percentage
of the population of PC12 cells from death. Concentrations of approximately 1 mM
of this aldehyde scavenger can rescue over 80% of the population of PC12 cells.
This study provides a basis for a new pharmacological treatment to reduce the
effects of secondary injury in the damaged and/or diseased nervous system. In
particular, we describe the need for new drugs that possess aldehyde scavenging
properties but do not interfere with the regulation of blood pressure. Copyright
2006 Wiley-Liss, Inc.

PMID: 16619236 [PubMed - indexed for MEDLINE]

Finally, the side effects of hydralazine are detailed at http://www.drugs.com/cons/hydralazine_systemic.html

ALL drugs have side effects.