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Anavex Advances Drug Candidates for Treatment of Epilepsy - Results in epilepsy animal models demonstrate that ANAVEX 2-73 and its active metabolite ANAVEX 19-144 have potent anticonvulsant, anti-amnesic and neuroprotective properties
Anavex Advances Drug Candidates for Treatment of Epilepsy

 

PRZOOM - /newswire/ - Geneva, Switzerland, 2008/01/15 - Results in epilepsy animal models demonstrate that ANAVEX 2-73 and its active metabolite ANAVEX 19-144 have potent anticonvulsant, anti-amnesic and neuroprotective properties.

   
 
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Anavex Life Sciences Corp. ("ANAVEX") (OTCBB: AVXL) today announced promising developments with ANAVEX 2-73 and ANAVEX 19-144, the company's lead drug candidates to treat epilepsy. During recent pre-clinical animal studies, ANAVEX 2-73 and ANAVEX 19-144 demonstrated significant anticonvulsant, anti-amnesic, neuroprotective and anti-depressant properties.

These activities involve muscarinic and sigma-1 receptor components, which is significant because it indicates a novel mechanism of action. Pioneered by ANAVEX, Sigma-1 receptors are a fairly new class of receptors -- molecules within a cell or on a cell surface to which substances (drugs or hormones) selectively bind, causing a change in the activity of the cell.

"Currently, there are no drugs available that truly control epilepsy or prevent epileptogenesis, a process that causes long-term tissue and cell damage as well as biochemical and physiological alterations to the brain. These alterations cause seizures and are linked with the progressive deterioration or death of the body's nerve cells," said Dr. Kontzalis, Chief Executive Officer for ANAVEX. "In addition, the drugs to treat epilepsy that are on the market today are often associated with cognitive, psychotic and memory problems. As such, we believe that novel drugs like ANAVEX 2-73 and ANAVEX 19-144, which have anti-epileptogenic, neuroprotective and anti-amnesic properties, are certain to have a major impact on the anti-epileptic drug market around the world."

Anticonvulsive properties were tested in epilepsy animal models with maximum electroshock (MES)- and pentylenetetrazole (PTZ)-induced generalized convulsions. In 90-100% of the treated animals versus the control group, both ANAVEX 2-73 and ANAVEX 19-144 exhibited extremely significant anticonvulsive action by providing almost complete protection from tonic seizures. This was accomplished without causing any memory deficits (amnesic effect) or mood disturbances (depression). Memory deficits and depressive phenomena are usually observed with the anti-epileptic drugs available today.

In PTZ-induced convulsions it was further observed that ANAVEX 19-144 is able to significantly prolong life during a seizure. Control-group animals died after three minutes and two seconds, while animals that received ANAVEX 19-144 were still alive after 50 minutes.

The pre-clinical study tested the anti-amnesic properties of ANAVEX 2-73 and ANAVEX 19-144 on mice, which were then submitted to short- and long-term memory tests, spontaneous alternation and passive avoidance respectively. Testing was conducted in pharmacological and pathological mouse models of amnesia. When the epilepsy drug candidates were administered to the mice, the compound dose reversed the learning deficits induced by the drugs scopolamine and dizocilpine and by the administration of amyloid beta peptide. The effects of ANAVEX 2-73 were linked to action at muscarinic and sigma-1 receptor sites because they were blocked by pre-injection of the sigma-1 receptor antagonist BD 1047.

The neuroprotective properties of ANAVEX 2-73 and ANAVEX 19-144 were studied in a non-transgenic mouse model of Alzheimer's disease. Central injection of amyloid beta peptide in mouse brains is known to induce histological and biochemical changes, oxidative stress and learning deficits within seven days. ANAVEX 2-73 or ANAVEX 19-144 administered once, either orally or by injection, prevented the appearance of amyloid beta peptide-induced learning or memory deficits. It also prevented oxidative stress, which damages and destroys cells, and nerve cell loss in sensitive areas of the brain that regulate learning, emotion and memory. In addition, the neuroprotective properties of ANAVEX 19-144 have been demonstrated, in a transient focal cerebral ischemia mouse model, to reduce the infarct area after ischemia by 28%.

The neuroprotective properties of ANAVEX 2-73 and ANAVEX 19-144 have been observed at very low doses (0.1-0.3 mg/kg). These doses are far below the levels that induce cholinergic- or sigma 1 receptor-related side effects, verifying the anticipated enhanced safety profile of the ANAVEX epilepsy drug candidates.
"We are confident that we have achieved proof-of-concept status for ANAVEX 2-73 and ANAVEX 19-144," said Dr. Vamvakides, Chief Scientific Officer of ANAVEX. "These latest results provide strong evidence as to the promise and potential of our epilepsy drug candidates, which have anti-epileptogenic action as well as an optimal efficacy and safety profile."

Ongoing pre-clinical studies, which are being conducted in collaboration with Universite Montpellier in France, are scheduled for completion by the end of May 2008.

Published results were presented at the Neuroscience 2007 conference in San Diego, California.

About Epilepsy
Epilepsy is a term used for recurring seizure disorder, a condition that is characterized by the tendency for an individual to have repeated nervous seizures (interruption of normal brain activity). By 2015, it is predicted that 6.4 million people will be living with epilepsy.

New drugs able to modify the onset of epilepsy (epileptogenesis) and progression of the disease, which have a novel mode of action that combines anticonvulsant, anti-amnesic, anti-depressant and neuroprotective properties as well as excellent safety and low toxicity,
are needed and have blockbuster potential. ANAVEX is developing drug candidates demonstrating the above properties.

About Sigma Receptors
Sigma receptors are a unique family of proteins, present mainly in the central nervous system (CNS) but also in various peripheral tissues. The receptors are classified in two subtypes: the sigma-1 and sigma-2. These subtypes are distinguishable pharmacologically, functionally and by molecular size. Sigma-1 receptors have been cloned and shown to be distinct from any known receptor class.

About ANAVEX
Anavex Life Sciences Corp. is an emerging biopharmaceutical company engaged in the discovery and development of novel drug targets for the treatment of cancer and neurological diseases. The company's proprietary SIGMACEPTOR™ Discovery Platform involves the rational drug design of compounds that fulfill specific criteria based on unmet market needs and new scientific advances. Selected drug candidates demonstrate high, non-exclusive affinity for sigma receptors, which are involved in the modulation of multiple cellular biochemical signaling pathways.

ANAVEX's SIGMACEPTOR™ -N program involves the development of novel and original drug candidates, targeting neurological and neurodegenerative diseases (Alzheimer's disease, epilepsy, depression, etc.). The company's lead drug candidates exhibit high, non-exclusive affinity for sigma receptors with strong evidence for anti-amnesic, neuroprotective, anti-apoptotic, anti-oxidative, anti-inflammatory, anti-convulsive, anti-depressant and anxiolytic properties.

ANAVEX SIGMACEPTOR™ -C program involves the development of novel and original drug candidates targeting cancer. The company's lead drug candidates exhibit high, non-exclusive affinity for sigma receptors with strong evidence for selective pro-apoptotic, anti-metastatic and low toxicity properties in various types of solid cancers such as colon, prostate, breast, lung, etc.

CONTACT:
Anavex Life Sciences Corp., Research & Business Development,
Shareholder & Media Relations, Toll-free: 1-866-505-2895, Outside North America

 
 
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Anavex Advances Drug Candidates for Treatment of Epilepsy

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