D-Serine Regulation: A Possible Therapeutic Approach for Central Nervous Diseases and Chronic Pain

Sethuraman, Rama; Lee, T. L.; Tachibana, Shinro

doi:10.2174/138955709788452630

Cited by 16 publications

(15 citation statements)

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“…A similar reduction in intracellular D-Ser concentration was observed after incubation with gabapentin and ( S )-pregabalin, which reduce intracellular Ca 2+ concentrations via inhibition of the α 2 -δ subunit of voltage-gated calcium channels [24]. Based upon these observations and the recent report identifying a relationship between reduced D-Ser concentrations and attenuated NMDA receptor activity in rat and mouse models [22], it is reasonable to assume that a ( 2S,6S )-HNK-associated reduction in D-Ser production should also result in reduced NMDA receptor activation and associated neurotoxicity, synaptic death and depression.…”

supporting

confidence: 53%

“…Variations in endogenous D-Ser levels have been correlated with a number of CNS diseases and pathological states, as increased levels of D-Ser in the CNS have been linked to amyotrophic lateral sclerosis and Alzheimer’s disease while decreases in CNS concentrations of D-Ser have been associated with schizophrenia [18]. Thus, modulation of SR activity is an area of pharmacological and clinical interest [18,22]. …”

mentioning

confidence: 99%

“…These results suggest that it is time to reassess the use of the ‘Ketamine Paradigm’ when studying the antidepressant effects produced by Ket and, perhaps, to create a new clinical paradigm based upon (2 S ,6 S )-HNK and the other understudied metabolites of Ket. In addition, the link between increased endogenous D-Ser plasma levels and CNS diseases and pathological states, such as Alzheimer’s and Parkinson’s diseases [18,22], suggests a broader clinical use for (2 S ,6 S )-HNK. Because the administration of (2 S ,6 S )-HNK produces decreased D-Ser production and improved neurogenesis, and the compound is orally bioavailable [Moaddel, Wainer 2014, unpublished data], (2 S ,6 S )-HNK should be a clinically useful addition to the treatment of these diseases as well as providing a template for new drugs and a new ‘Ketamine Metabolite Paradigm’.…”

mentioning

confidence: 99%

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What is hydroxynorketamine and what can it bring to neurotherapeutics?

Singh

Zarate

Moaddel

et al. 2014

Expert Review of Neurotherapeutics

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(R,S)-Ketamine was initially developed as an anesthetic agent and its pharmacological properties were determined on the basis of this clinical use. However, pharmacological studies in rat led to the development of the ‘Ketamine Paradigm’, whereby (R,S)-ketamine and its N-demethylated metabolite (R,S)-norketamine were deemed the active compounds whereas the other ketamine metabolites were considered inactive. Recent in vivo and in vitro studies with (2S,6S)-hydroxynorketamine, a previously identified ‘inactive’ metabolite, have demonstrated that this compound is an active and selective inhibitor of the α7 subtype of the nicotinic acetylcholine receptor and that this activity contributes to the pharmacological responses associated with the antidepressant activity of (R,S)-ketamine. Thus, it appears that it is necessary to reassess the ‘Ketamine Paradigm’ in regards to the use of sub-anesthetic doses of (R,S)-ketamine in the treatment of treatment-resistant depression.

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confidence: 53%

mentioning

confidence: 99%

mentioning

confidence: 99%

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What is hydroxynorketamine and what can it bring to neurotherapeutics?

Singh

Zarate

Moaddel

et al. 2014

Expert Review of Neurotherapeutics

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“…Because d-Ser also acts as an agonist of N-methyl-d-aspartate (NMDA) receptormediated neurotransmission in the brain, it may be useful as innovative pharmacologic strategy in schizophrenia and pain [205]. A strain of protozoa (Drosophila melanogaster) has developed a transport mechanisms with adaptive specialization in the absorption and brain functions of d-Ser and other DAA that may be involved in neuronal functions [206].…”

Section: 4mentioning

confidence: 99%

Origin, Microbiology, Nutrition, and Pharmacology of D‐Amino Acids

Friedman

2010

Chemistry & Biodiversity

162

108

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Exposure of food proteins to certain processing conditions induces two major chemical changes: racemization of all L-amino acids (LAAs) to D-amino acids (DAAs) and concurrent formation of cross-linked amino acids such as lysinoalanine (LAL). The diet contains both processing-induced and naturally-formed DAA. The latter include those found in microorganisms, plants, and marine invertebrates. Racemization impairs digestibility and nutritional quality. Racemization of LAA residues to their D-isomers in food and other proteins is pH-, time-, and temperature-dependent. Although racemization rates of LAA residues in a protein vary, relative rates in different proteins are similar. The nutritional utilization of different DAAs varies widely in animals and humans. Some DAAs may exert both adverse and beneficial biological effects. Thus, although D-Phe is utilized as a nutritional source of L-Phe, high concentrations of D-Tyr in such diets inhibit the growth of mice. Both D-Ser and LAL induce histological changes in the rat kidney. The wide variation in the utilization of DAAs is illustrated by the fact that, whereas D-Meth is largely utilized as a nutritional source of the L-isomer, D-Lys is not. Similarly, although L-CysSH has a sparing effect on L-Meth when fed to mice, D-CysSH does not. Since DAAs are consumed as part of their normal diet, a need exists to develop a better understanding of their roles in foods, microbiology, nutrition, and medicine. To contribute to this effort, this overview surveys our present knowledge of the chemistry, nutrition, safety, microbiology, and pharmacology of DAAs. Also covered are the origin and distribution of DAAs in food and possible roles of DAAs in human physiology, aging, and the etiology and therapy of human diseases.

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“…Thus, several studies have found an association between the activity of serine racemase and schizophrenia (Labrie et al 2009), Alzheimer's disease (Hashimoto et al 2004), and age-related memory loss (Mothet et al 2006). D-Ser may also be useful as an innovative pharmacologic strategy in the treatment of these diseases (Coyle et al 2010;Sethuraman et al 2009), as well as for ameliorating pain (Muth-Selbach et al 2004) and treating anxiety disorders (Matsuda et al 2010). Further research is needed to clarify the consequences of D-Ser exposure on pathways implicated in neuronal functions and neurodegenerative disorders (Davidson et al 2009).…”

Section: D-serinementioning

confidence: 99%

Nutritional and medicinal aspects of d-amino acids

2011

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This paper reviews and interprets a method for determining the nutritional value of D-amino acids, D-peptides, and amino acid derivatives using a growth assay in mice fed a synthetic all-amino acid diet. A large number of experiments were carried out in which a molar equivalent of the test compound replaced a nutritionally essential amino acid such as L-lysine (L-Lys), L-methionine (L-Met), L-phenylalanine (L-Phe), and L-tryptophan (L-Trp) as well as the semi-essential amino acids L-cysteine (L-Cys) and L-tyrosine (L-Tyr). The results show wide-ranging variations in the biological utilization of test substances. The method is generally applicable to the determination of the biological utilization and safety of any amino acid derivative as a potential nutritional source of the corresponding L-amino acid. Because the organism is forced to use the D-amino acid or amino acid derivative as the sole source of the essential or semi-essential amino acid being replaced, and because a free amino acid diet allows better control of composition, the use of all-amino-acid diets for such determinations may be preferable to protein-based diets. Also covered are brief summaries of the widely scattered literature on dietary and pharmacological aspects of 27 individual D-amino acids, D-peptides, and isomeric amino acid derivatives and suggested research needs in each of these areas. The described results provide a valuable record and resource for further progress on the multifaceted aspects of D-amino acids in food and biological samples.

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D-Serine Regulation: A Possible Therapeutic Approach for Central Nervous Diseases and Chronic Pain

Cited by 16 publications

References 0 publications

What is hydroxynorketamine and what can it bring to neurotherapeutics?

What is hydroxynorketamine and what can it bring to neurotherapeutics?

Origin, Microbiology, Nutrition, and Pharmacology of D‐Amino Acids

Nutritional and medicinal aspects of d-amino acids

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