How does reverse tolerance work?

Sensitization, also referred to as reverse tolerance, is a phenomenon in which following repeated exposure to the same dose of a particular drug of abuse, a specific behavioral, physiological, or cellular response increases, rather than decreases, over time.

How do NMDA receptor antagonists work?

NMDA antagonists bind to NMDA receptors and prevent the binding of glutamate, thereby preventing the release of calcium into the nerve cells.

Do NMDA antagonists increase glutamate?

Preliminary preclinical and unpublished clinical data suggest that postsynaptic NMDA receptor antagonism increases presynaptic glutamate release (i.e., glutamate “surge”).

Which drugs cause sensitization?

Most major drugs of abuse are capable of inducing sensitization, including psychostimulants (amphetamine, cocaine, MDMA, cathinone, fencamfamine, methylphenidate, phenylethylamine, etc.), opiates, phencyclidine, alcohol, and nicotine.

How does drug sensitization occur?

Drug sensitization occurs in drug addiction, and is defined as an increased effect of drug following repeated doses (the opposite of drug tolerance). Such sensitization involves changes in brain mesolimbic dopamine transmission, as well as a protein inside mesolimbic neurons called delta FosB.

How does memantine block glutamate?

Memantine binds weakly to the ion channel-binding site on the NMDA receptor when it is in an open state and thus blocks the tonic pathological activation, induced by micromolar glutamate concentrations.

How does NMDA affect glutamate?

The NMDA receptor is so named because the agonist molecule N-methyl-D-aspartate (NMDA) binds selectively to it, and not to other glutamate receptors. Activation of NMDA receptors results in the opening of the ion channel that is nonselective to cations, with a combined reversal potential near 0 mV.

What drugs block NMDA receptors?

Commercially available NMDA-receptor antagonists include ketamine, dextromethorphan, memantine, and amantadine. The opioids methadone, dextropropoxyphene, and ketobemidone are also antagonists at the NMDA receptor.

What do NMDA antagonists do to glutamate?

Competitive NMDA antagonists bind directly to the glutamate site of the NMDA receptor to inhibit the action of glutamate. Non-competitive antagonists block the NMDA-associated ion channel in a use-dependent manner. Other sites on the NMDA receptor susceptible to antagonism are the glycine site and the polyamine site.

What do glutamate antagonists do?

Low doses of glutamate antagonists have been shown to slow down the rate of nerve cell loss in the brain, thereby slowing down the progression of Parkinson’s. Glutamate antagonists work by inhibiting the activity of glutamate receptors in the brain.

What is NMDA antagonist in Alzheimer’s?

NMDA Receptor Antagonists and Alzheimer’s. In this Article. NMDA (short for N-methyl-D-aspartate) receptor antagonists are a class of drugs that may help treat Alzheimer’s disease, which causes memory loss, brain damage, and, eventually, death. There’s no cure for Alzheimer’s, but some drugs may slow it down.

What are NMDA drugs used to treat?

In this Article. NMDA (short for N-methyl-D-aspartate) receptor antagonists are a class of drugs that may help treat Alzheimer’s disease, which causes memory loss, brain damage, and, eventually, death.

What happens when glutamate is docked at an NMDA receptor?

When glutamate is “docked” at an NMDA receptor, it passes calcium into the cell, carrying the electrical or chemical signal that last step. This is important for learning and memory. If you have Alzheimer’s disease, your cells can make too much glutamate. When that happens, the nerve cells get too much calcium, and that can speed up damage to them.

How does memantine (Namenda XR) work?

Most Alzheimer’s drugs focus on another chemical messenger known as acetylcholine. They keep acetylcholine levels high to keep nerve cells firing and slow the progress of the disease. But doctors do use one NMDA receptor antagonist: memantine (Namenda XR).