NMDA Receptor Modulators
Encyclopedia
NMDA receptor modulators (glutamate modulators) are a new form of antipsychotic
that are in Phase II FDA study. The first compound studied was glycine
which was hypothesized by Daniel Javitt after observation that people with phencyclidine
(PCP)-induced psychosis
were lacking in glutamate
transmission. (PCP is an NMDA receptor antagonist
that blocks glutamate) In giving glycine to people with PCP-induced psychosis a recovery rate was noted. From there, it was hypothesized that people with psychosis from schizophrenia
would benefit from increased glutamate transmission and glycine
was added with strong recovery rates noted especially in the area of negative and cognitive symptoms. Glycine
, however, sporadic results aside (dose 60 g/day or 0.8 g/kg, approximately the amount in 300 g of gelatin powder or two kilograms of sunflower seeds) remains an adjunct antipsychotic
and an unworkable compound. However, the Eli Lilly and Company
study drug LY2140023 is being studied as a primary antipsychotic
and is showing strong recovery rates, especially in the area of negative and cognitive symptoms of schizophrenia
. Tardive dyskinesia
, diabetes and other standard complications have not been noted:
Other NMDA receptor modulators are being studied and this modality of treatment may once approved as antipsychotic
medications gradually replace the current (dopaminergic) antipsychotics.
Antipsychotic
An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
that are in Phase II FDA study. The first compound studied was glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
which was hypothesized by Daniel Javitt after observation that people with phencyclidine
Phencyclidine
Phencyclidine , commonly initialized as PCP and known colloquially as angel dust, is a recreational dissociative drug...
(PCP)-induced psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
were lacking in glutamate
Glutamic acid
Glutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...
transmission. (PCP is an NMDA receptor antagonist
NMDA receptor antagonist
NMDA receptor antagonists are a class of anesthetics that work to antagonize, or inhibit the action of, the N-methyl d-aspartate receptor . They are used as anesthesia for animals and, less commonly, for humans; the state of anesthesia they induce is referred to as dissociative anesthesia...
that blocks glutamate) In giving glycine to people with PCP-induced psychosis a recovery rate was noted. From there, it was hypothesized that people with psychosis from schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
would benefit from increased glutamate transmission and glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
was added with strong recovery rates noted especially in the area of negative and cognitive symptoms. Glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
, however, sporadic results aside (dose 60 g/day or 0.8 g/kg, approximately the amount in 300 g of gelatin powder or two kilograms of sunflower seeds) remains an adjunct antipsychotic
Antipsychotic
An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
and an unworkable compound. However, the Eli Lilly and Company
Eli Lilly and Company
Eli Lilly and Company is a global pharmaceutical company. Eli Lilly's global headquarters is located in Indianapolis, Indiana, in the United States...
study drug LY2140023 is being studied as a primary antipsychotic
Antipsychotic
An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
and is showing strong recovery rates, especially in the area of negative and cognitive symptoms of schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
. Tardive dyskinesia
Tardive dyskinesia
Tardive dyskinesia is a difficult-to-treat form of dyskinesia that can be tardive...
, diabetes and other standard complications have not been noted:
Treatment with LY2140023, like treatment with olanzapine, was safe and well-tolerated; treated patients showed statistically significant improvements in both positive and negative symptoms of schizophrenia compared to placebo (P o 0.001 at week 4). Notably, patients treated with LY2140023 did not differ from placebo-treated patients with respect to prolactin elevation, extrapyramidal symptoms or weight gain. These data suggest that mGlu2/3 receptor agonists have antipsychotic properties and may provide a new alternative for the treatment of schizophrenia.
Other NMDA receptor modulators are being studied and this modality of treatment may once approved as antipsychotic
Antipsychotic
An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...
medications gradually replace the current (dopaminergic) antipsychotics.