Ampakines
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Ampakines
Ampakines are a class of drugs that modulate neurotransmitters in the brain. One of the major neurotransmitters is glutamate, and a reduced level of glutamate-mediated excitatory stimulation has been implicated in Alzheimer’s disease, schizophrenia, and a number of other diseases and disorders. The name is partially derived from AMPA, a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor structure in brain neurons. The drugs influence how those receptors get signals. They "attenuate desensitization of AMPA receptor currents".
Neurotransmitters bind to proteins, called receptors, located on the surface of the receiving neurons. This binding then triggers subsequent cellular events in the receiving neurons. Ampakines influence the receptors. Ampakines enhance the functioning of a receptor, called the AMPA receptor, which plays a key role in memory formation and communication within and between different regions of the brain. One article put it this way: " Brain imaging in primates has shown that ampakines expand cortical networks engaged by a complex task; coupled with behavioral data, these findings provide evidence for the possibility of generating new cognitive capabilities."
The hope and promise of ampakines is that they will produce cognitive benefits when used as drugs. There is research interest in memory enhancement, stroke therapy, Alzheimers treatment, sleep deprivation aid, and other therapeutic uses of ampakines. Several of these possibilities have been tested with positive results in preclinical models; preliminary clinical work has also been encouraging. Further, scientists feel that ampakines can change information encoding and organization in the brain.
Ampalex® has been shown in preclinical trials to be highly promising in improving cognitive function, and has been relatively free of serious side effects. Reseach has suggested that the ampakine CX717 may help protect against respiratory depression in patients under the anesthesia fentanyl. A depressed repiratory system and apnea are threats for people under anesthesia. Clinical trials are underway to test ampakines to help surgery patients with breathing.
Some researchers divide the various kinds of ampakines into Type I and Type II based on how much impact the drug has on AMPA receptors in the brain. Type I, the “low-impact” compounds, include CX-717 and Ampalex. Type II, the “high-impact” compounds include CX-1632. Calling them low-impact and high-impact may be misleading, however. They don’t just differ on how big their effect is. Both types increase responses in AMPA glutamate receptors. But Type I prolong the responses while Type II increase the amplitude. Scientists have figured out that’s because they work at different receptor sites in the neuron.
Researchers at the University of California, Irvine proposed cognitive enhancement drugs can be put into one of three categories: (1) those that mainly operate on primary psychological states such as modafinil and methylphenidate, (2) those that improve memory encoding and which may find use in treatment of dementia, and (3) those that may affect the integration of cognitive operations. These drugs may expand cortical networks inside the working brain, thereby making more raw power available for thinking. Ampakines are part of this third category.
Researchers have found compounds that work on the brain’s nicotinic receptors that regulate release of the glutamate. Ampakines, also work on the glutamate receptors but through a different mechanism - by binding to a different place on the neuron.
There is also interest in pain relief. But don't we already have enough analgesics on the market? Yes, but the exciting thing about ampakines is that their analgesic effect is produced by a different biochemical pathway. Opioid drugs for pain can suppress the respiratory system. Ampakines don't do that; indeed they have been tested as rescue drugs for people with opioid overdoses. Tests with the ampalines CX546 and CX516 show they can reduce sensitivity to pain due to neuropathic (nerve damage) problems and inflammation.
Important neurotransmitters in regulating wakefullness and sleepiness include norepinephrine, serotonin, glutamate, acetylcholine, histamine,and the neuromodulators hypocretin-orexins and adenosine. These affect the signal transducion in the brain. The ampakine drugs seem to modulate some of the brain's glutamate receptors. Some of these receptors are called metabotropic glutamate receptors and it is believed that stimulating those can help enhance attention, although scientists are not really sure.
Piracetam, a drug popular with the "smart drug" movement, may be classified as an ampakine. Piracetam seems to have different biochemical effects, and has been found to help facilitate memory in humans. Animal studies with controlled learning patterns have shown piracetam promotes memory consolidation.
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