New Scientist Sept 2001 describes AM-36 for reducing cell suicide resulting from strokes.  But it may take 8 years to get the drug to market. 

        Other references from the WEB include the following:

New stroke drug minimises brain damage  
from : http://www.sciencenow.org.au/Fresh2001/Jennifer_Callaway.htm

An Australian drug that has the potential to treat stroke survivors is under development in the UK by a UK-based biotechnology company DevCo. 

The drug, known as AM-36, can minimise brain damage and physical impairments caused by strokes - Australia’s leading cause of disability. Dr Jenny Callaway and her colleagues at Monash University discovered  the new drug in collaboration with Melbourne-based biotechnology company AMRAD who have licenced the drug to DevCo.

“It won’t stop strokes from happening,” says Dr Callaway. “But we are confident that it will stop much of the damage that occurs in the brain after a stroke – particularly if the drug is given within hours of the stroke occurring.”

Trials in rats reduced stroke brain damage by over 65%, so the team believes it could be very effective in humans.

 “At present, there is no clinically available drug that can reduce the amount of damage in stroke survivors – whether they are old or young,” says Dr Callaway. “AM-36 potentially will fill that gap and reduce the heavy and expensive burden of care placed on families and health care services.”

Some 37 000 Australians and their families are affected by stroke each year. Stroke most often occurs when a blood vessel in the brain becomes blocked.

The blockage cuts off the vital supply of oxygen and nutrients to the brain, causing brain cells to die which results in brain damage, and/or physical and mental problems.

“After a stroke, it is common for free radicals, products of normal cellular processes, to build up and cause brain damage,” explains Dr Callaway. “But if AM-36 can be administered ideally within 6 hours of a stroke, we’re optimistic that it could prevent much of that build-up, and rescue brain cells from the ensuing damage.”

A unique feature of AM-36 is it prevents brain cells from dying through multiple actions.

This research was in collaboration with and financially supported by AMRAD Corporation Limited and the NH&MRC.

Corey Nassau

A collaborative effort between scientists in Monash University's Pharmacology and Chemistry departments has led to the development of a new drug that could significantly decrease the number of people who experience sustained physical and mental disability after a stroke.

According to Pharmacology head Professor Bevyn Jarrott, AM-36 is unique not only because it utilises a multifunctional strategy to actively rescue brain cells, but also because of the 'time window' for care it could offer to sufferers of stroke.

"With a stroke, unlike a heart attack, it is often hours before medical attention is received as the symptoms are not always clear. AM-36 has been designed with this therapeutic intervention in mind and has been successfully administered in an animal model of stroke as late as four to six hours after the trauma," Professor Jarrott said.

Each year, more than 40,000 Australians are affected by stroke, which is now recognised as the country's leading single cause of disability and the second greatest cause of death after heart disease.

A stroke occurs when the supply of blood is significantly reduced to either the whole or part of the brain. Most commonly this occurs as a result of a clot in the artery that supplies blood to that region, resulting in restricted blood flow.

According to Professor Philip Beart of Monash's Pharmacology department, who was also instrumental in the development of AM-36, a series of cascading toxic events occur after a stroke. It is during this time, he says, that the areas of the brain surrounding the clot are at an increased risk of cell death caused by free radicals or toxins.

"The strategy that our drug employs is actually to save the cells from dying during the oxidative imbalance," Professor Beart said.

The Australian pharmaceutical company AMRAD Corporation Ltd, in a cross-licensing agreement with the UK-based company DevCo Pharmaceuticals, is supporting the development of the drug.

Further study of the AM-36 group of compounds has also shown that some related compounds could be effective for a number of other neurodegenerative diseases such as Parkinson's disease, Alzheimer's or even Huntington's chorea.

Incorporation of sodium channel blocking and free radical scavenging activities into a single drug, AM-36, results in profound inhibition of neuronal apoptosis

¹ Department of Pharmacology, Monash University, Victoria, 3800, Australia

^*Correspondence: Jennifer K. Callaway, Department of Pharmacology, P.O. Box 13E, Monash University, Victoria 3800, Australia. E-mail: Jennifer.Callaway@med.monash.edu.au

1. AM-36 is a novel neuroprotective agent incorporating both antioxidant and Na⁺ channel blocking actions. In cerebral ischaemia, loss of cellular ion homeostasis due to Na⁺ channel activation, together with increased reactive oxygen species (ROS) production, are thought to contribute to neuronal death. Since neuronal death in the penumbra of the ischaemic lesion is suggested to occur by apoptosis, we investigated the ability of AM-36, antioxidants and Na⁺ channel antagonists to inhibit toxicity induced by the neurotoxin, veratridine in cultured cerebellar granule cells (CGC's).
   
2. Veratridine (10 – 300 µM) concentration-dependently reduced cell viability of cultured CGC's. Under the experimental conditions employed, cell death induced by veratridine (100 µM) possessed the characteristics of apoptosis as assessed by morphology, TUNEL staining and DNA laddering on agarose gels.
   
3. Neurotoxicity and apoptosis induced by veratridine (100 µM) were inhibited to a maximum of 50% by the antioxidants, U74500A (0.1 – 10 µM) and U83836E (0.03 – 10 µM), and to a maximum of 30% by the Na⁺ channel blocker, dibucaine (0.1 – 100 µM). In contrast, AM-36 (0.01 – 10 µM) completely inhibited veratridine-induced toxicity ( IC₅₀ 1.7 (1.5 – 1.9) µM, 95% confidence intervals (CI) in parentheses) and concentration-dependently inhibited apoptosis.
   
4. These findings suggest veratridine-induced toxicity and apoptosis are partially mediated by generation of ROS. AM-36, which combines both Na⁺ channel blocking and antioxidant activity, provided superior neuroprotection compared with agents possessing only one of these actions. This bifunctional profile of activity may underlie the potent neuroprotective effects of AM-36 recently found in a stroke model in conscious rats.
   

British Journal of Pharmacology (2001) 132, 1691 – 1698