Therapeutic uses Various neurodegenerative diseases have been associated with excessive NMDA receptor activation meant to mediate calcium dependent neurotoxicity. Researchers have examined many different NMDA antagonists and their therapeutic efficacy, none of which have concluded to be both safe and effective. For years, researchers have been investigating the effects of an open channel block, memantine, as a treatment option for neurotoxicity. They hypothesized that the faster blocking and unblocking rates, and overall kinetics, of memantine could be the underlying reason for the clinical tolerance. As an uncompetitive antagonist, memantine should bring NMDA levels close to normal despite high glutamate concentration. Based on this information, researchers speculated that some day memantine could be used as an open channel block to prevent increasing glutamate levels associated with neurotoxicity with little to no side effects compared to other treatment options. Alzheimer's disease Alzheimer's disease, a specific neurodegenerative disorder, is linked to glutaminergic neurotransmission interruptions that are believed to result in the staple cognitive symptoms of Alzheimer's. Researchers suggest that noncompetitive NMDA receptor agonists can be used to aid in the management of these symptoms without producing severe side effects. As one of the only drugs approved for Alzheimer's treatment, memantine has been shown to allow excitatory post synaptic currents to remain unaffected while decreasing the incidence and amplitude of inhibitory post-synatpic currents. Evidence supports the hypothesis that both the strong voltage dependency and fast kinetics of memantine may be responsible for the decreased side effects and cognitive progress. Cystic fibrosis Cystic fibrosis is a progressive, genetic disease that is linked to CF transmembrane regulator (CFTR) dysfunction. Blockage of this channel by certain cytoplasmic, negatively-charged substances results in reduced chloride ion and bicarbonate anion transport, as well as reduced fluid and salt secretion. This results in a buildup of thick mucus, which is characteristic of cystic fibrosis. Pharmacology Anesthetics<unk> s are essential in the field of anesthetics. Sodium channel inhibitors are used as both antiepileptics and antiarrhythmics, as they can inhibit the hyper-excitable tissues in a patient. Introducing specific sodium<unk> s into a tissue allows for the preferential binding of the<unk>  to sodium channels, which results in an ultimate inhibition of the flow of sodium into the tissue. Over time, this mechanism leads to an overall decrease in tissue excitation. Prolonged hyperpolarization interrupts normal channel recovery and allows for constant inhibition, providing dynamic control of the anesthetics in a given setting. Alzheimer's disease Excessive exposure to glutamate leads to neurotoxicity in patients with Alzheimer's disease. Specifically, over-activation of NMDA-type glutamate receptors have been linked to neural cell excitotoxicity and cell death. A potential solution to this is a decrease in NMDA receptor activity, without interfering so drastically as to cause clinical side effects. In an attempt to prevent further neurodegeneration, researchers have used memantine, an open channel block, as a form of treatment. Thus far, the use of memantine in patients with Alzheimer's disease quickly results in clinical progress across many different symptoms. Memantine is thought to work effectively due to its ability to quickly modify its kinetics, which prevents buildup in the channel and allows normal synaptic transmission. Other<unk> s have been found to block all NMDA receptor activity, leading to adverse clinical side effects. CFTR channel dysfunction Cystic Fibrosis transmembrane regulators (CFTRs) function in chloride ion, bicarbonate anion, and fluid transport. They are expressed primarily in apical membranes of epithelial cells in respiratory, pancreatic, gastrointestinal, and reproductive tissues. Abnormally-elevated CFTR function results in excessive fluid secretion. High-affinity CFTR inhibitors, such as CFTRinh-172 and GlyH-101, have been shown to be efficient in treatment of secretory diarrheas. Theoretically, CFTR<unk> s may also be useful as male contraceptives. CFTR channels mediate bicarbonate anion entry which is essential for sperm capacitation. Various types of substances have been known to block CFTR chloride ion channels. Some of the best-known and studied substances include sulfonylureas, arylaminobenzenoates, and disulfonic stilbenes. These<unk> s are side-dependent as they enter the pore exclusively from the cytoplasmic side, voltage-dependent as hyperpolarized membrane potentials favor negatively-charged substance entry into the pore from the cytoplasmic side, and chloride ion concentration-dependent as high extracellular chloride ions electrostatically repel negatively-charged<unk> s back into the cytoplasm.
Channel blocker
Channel opener
Channel modulator
Chloride channel opener
Calcium channel blocker
Beta-adrenergic agonist
Muscle relaxant
GABA analogue