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Ampakines

Ampakines were developed as an attempt to improve the response of synapses; the hope is that they could improve cognition in any disease with impairment of cognition. Cortex Pharmaceuticals (Irvine, Calif.) is investigating drugs including one called "CX516(AmpalexTM). They might "compensate for low levels of glutamate", which is good because Alzheimer's might involve low glutamate. These have a ways to go in research, but they are quite different from existing treatments. They might eventually complement other treatments. The drugs are designed to attach themselves to sites on nerve cells called AMPA receptors. Since those cells communicate via the neurotransmitter glutamate, the drugs boost the signals. This is exciting stuff; you could follow the company's progress.

SOURCE: Cortex Pharmaceuticals, Inc.
Cortex Pharmaceuticals' AMPAKINEs Increase Neurotrophin Expression - Increased Neurotrophic Factors May Slow or Possibly Stop the Normal Brain Ageing Process.

Research conducted at the University of California, Irvine (UCI) demonstrates that AMPAKINEŽs can increase the production of the important neurotrophic factors BDNF (brain derived neurotrophic factor) and NGF (neuronal growth factor) in critical areas of the brain involved in memory. Cortex Pharmaceuticals, Inc. announced (1/18/00) the publication of a paper reporting these findings, Julie Lauterborn, Gary Lynch, Peter Vanderklish, Amy Arai and Christine Gall "Positive Modulation of AMPA Receptors Increases Neurotrophin Expression by Hippocampal and Cortical Neurons,'' in the January, 2000 issue of the Journal of Neuroscience.

Experiments were conducted on slices of brain tissue maintained in culture and in aged rats and mice. Increases in the expression of BDNF were observed in both species. The research was sponsored in part by Cortex. As part of the normal ageing process, there is a decline in the production of neurotrophins, particularly BDNF. This decrease results in less healthy neurons which are characteristically smaller than young nerve cells. A number of researchers have demonstrated that infusion of neurotrophins may restore the size and function of aged neurons. "One of the most important aspects of this study is that it shows that AMPAKINEs that can be dosed in the form of a pill can increase the production of neurotrophic factors,'' stated Vincent F. Simmon, Ph.D., President and Chief Executive Officer of Cortex. "AMPAKINEs should overcome the problems associated with the direct application of neurotrophic factors, which may lead to aberrant nerve cell growth and connections. A pill is also far less invasive than direct administration of neurotrophic factors by injection of protein or neurotrophin-producing cells into the brain.''

Cortex and its collaborators at UC Irvine are in the process of initiating a long term experiment in which rats will receive an AMPAKINE in their drinking water for four to eight months. They will be evaluating the performance of these animals in memory tasks as well as analyzing their brain tissue. They expect the results to begin to be available by the end of this year. "Most neuroscientists believe that increasing the level of neurotrophic factors will slow or possibly stop the effects of brain aging. The experiment being initiated at Cortex is designed to determine if this assumption is correct. Needless to say, we hope they are right.''

Ampakines are a new class of drugs that improve memory. According to researcher Gary Lynch of the University of California-Irvine, who has studied ampakines since 1991, they increase activity in the brain's cortex. Lynch and Gary Rogers, head of drug development at Cortex Pharmaceuticals in Southern California, have developed an ampakine drug, Ampalex, that increases levels of a specific neurotransmitter in the brain, AMPA-glutamate. In a recent 16-day animal study, animals not taking Ampalex scored 50% on a variety of memory tests, while those taking the drug scored 85%. In humans, Ampalex has been tested in Germany and Sweden on 54 people, age 21 to 73, with normal brain function. Compared with those not taking the drug, those using Amaplex scored twice as well on short-term memory tests.

Update (5/05): Cortex has an ampakine drug, CX717 that may have multiple applications (narcolepsy, jet lag, AD) because it has general inter-neuron communication enhancement ability. There don't seem to be any body activation (amphetamine-like) side effects. Gary Lynch at UC seems to be the person central to recent findings.

See also: Memantine

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