D-cycloserine, ≥90%

Partial agonist at the glycine modulatory site of NMDA glutamatergic receptors; antibiotic against Gram-negative bacteria.

Chemical Name(R)-4-amino-1,2-oxazolidin-3-one
SynonymsD-4-amino-3-isoxazolidone, D-oxamycin, Seromycin, K300, NJ-21
CAS #68-41-7
FormYellow powder
Molecular FormulaC3H6N2O2
Molecular Weight102.1
E 1%402 (226 nm)
[α]D23+115° (c=1.0%, water)
Solubility Soluble to 100 mg / mL in deionized water
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This Material is Sold For Research Use Only. Terms of Sale Apply. Not for Human Consumption, nor Medical, Veterinary, or Household Uses.

Chemical Information:

CAS Number:68-41-7
Purity:≥99%
Molecular Weight:294.18 g/mol
Melting Point:147°C
Molecular Formula:C3H6N2O2
Synonyms: D-4-amino-3-isoxazolidone, D-oxamycin, Seromycin, K300, NJ-21
PubChem CID:6234
SMILES:O=C1NOC[C@H]1N

Technical Information:

Application:Partial agonist at the glycine modulatory site of NMDA. Glutamatergic receptors; antibiotic against Gram-negative bacteria
Appearance:Yellow powder
Physical State:Solid
Solubility:Soluble to 100 mg / mL in deionized water
Storage:Stable for at least four years when stored as unopened and desiccated at -20°C
Stability:Deteriorates in presence of water. It is recommended to prepare solutions immediately before use because neutral or acidic solutions are unstable.

Modes of Action:

D-Cycloserine (commonly referred to simply as Cycloserine) is a structural analogue of D-alanine. It is produced by strains of Streptomyces orchidaceus or S.garphalus, and functions as a broad spectrum antibiotic. [1] [2] The drug interferes with bacterial cell wall synthesis by competitively inhibiting L-alanine racemase and D-alanine:D-alanine ligase, thereby impairing peptidoglycan formation. It may act either as a bactericidal or bacteriostatic, depending on its concentration at the infection site and the susceptibility of the organism. [3]

It is active against species of mycobacterium including M. tuberculosis, M. bovis, some strains of M. kansasii, M. marinum, M. ulcerans, M. avium complex (MAC), M. smegmatis, and M. intracellulare. [4] In terms of gram-positive and gram-negative bacteria, D-Cycloserine is effective against Staphylococcus aureus, Enterobacter, and Escherichia coli. [5] D-Cycloserine was included on the WHO’s 2015 (19th edition) list of essential medicines. [6]

D-Cycloserine acts as a partial agonist at glycine modulatory sites of NMDA receptors, with a maximum efficiency of around 40-50% that of glycine, as shown on Xenopus oocyte preparations. [7] Studies have indicated that D-Cycloserine acts as an NMDA receptor agonist on receptors containing GluNR2C subunits [8] and may act as an agonist or antagonist at NMDA receptors containing NR2A or NR2B subunits. [9]

At low doses, D-Cycloserine acts as a cognitive enhancer and has been shown to improve memory and learning in several experimental models of disease and cognitive deficits. [10] [11] At high and intermediate doses, D-Cycloserine acts as an anticonvulsant. [12]

Pharmcokinetics have been reported for D-Cycloserine in humans. [13] Additionally, methods have been reported for quantifying Cycloserine and its analogue Acetylacetonylcycloserine through HPLC [14] and a colorimetric method for determination of  cycloserine in biological fluids. [15]

D-Cycloserine is being researched as a potential future medication for OCD and a range of other neurological disorders, including PTSD, body-dysmorphic disorder, anxiety, and schizophrenia. [16]

Further Scientific Research:

Please note that this is not a comprehensive account of the scientific research on D-Cycloserine to date. We have made a humble attempt to convey some of the most relevant research on the subject to date, in a variety of applications. For a full scope of the relevant data, please visit PubMed.gov.

Interestingly, a large number of publications on the use of D-Cycloserine have appeared in this year (2017), attesting to increasing interest in this compound in the fields of neuroscience, psychiatry, and biochemical pathway research.

Clinical reviews:

An early 2017 review on the neuropsychiatric effects of antimicrobial agents elucidated further on D-Cycloserine’s function as an NMDA agonist. [17]

In mid-2017, a group of 35 researchers in the fields of psychiatry and neuroscience published a review and meta-analysis on the effects of D-Cycloserine (DCS) in the augmentation of cognitive behavioral therapy for anxiety, OCD, and PTSD. Individual data was obtained from 21 clinical eligible trials, representing 1047 participants. Results showed a statistically significant improvement in those receiving DCS from pretreatment to post-treatment, when controlling for antidepressant use. [18]

A July 2017 review published in Current Neuropharmacology examined the previous literature pertaining to D-Cycloserine’s effects on memory and plasticity, and specifically, its potential application in schizophrenia. In the review, Goff found significant evidence pointing to the ability of DCS to enhance memory consolidation and learning, and to improve negative symptoms in schizophrenia patients, through its actions as an agonist at at NMDA receptors. [19]

A 2016 systematic review by Schade and Paulus found substantial evidence indicating D-Cycloserine’s potential for future use in both psychiatric diseases and neurological diseases (Alzheimer’s), again through its modulation of NMDA receptor action. [20]

Human Studies:

There have been numerous clinical trials on the antibiotic effects of D-Cycloserine, both prior to its medical use and in the following years. The studies we’ve included below pertain to its use in neuroscience and biochemical research for cognitive and neurological disorders. Again, this is by no means a comprehensive account of the extensive research available – we are simply presenting a small selection of recent/interesting trials for your consideration. 

In 2013, Heresco-Levy et al. published the results of their study which looked into the effects of DCS on patients with treatment-resistant depression. Findings showed possible NMDAR antagonism at high doses. Results showed 54% of patients who had a ≥50% HAMD score reduction, compared to 15% of placebo, along with a significant glycine serum levels interaction. [21]

A 2017 study by Wink et al. investigated the effects of d-Cycloserine in the social skills training of autism spectrum disorder. The placebo-controlled study found statistically significant outcomes compared to placebo after 10 weeks of administration. [22]

 Regarding the cognitive enhancing potential of d-Cycloserine, in 2015 a group of researchers showed that the compound is effective in augmenting NMDA receptor signaling and boosting neuroplasticity in healthy subjects. [23]

A 2014 study using unique learning models investigated the use of DCS for enhancing memory, decision-making, and learning in healthy participants. “D-cycloserine shifted decision-making towards a more optimal integration of the learnt and the explicitly shown information, in the absence of a direct learning effect. (Scholl, 2014)” [24]

 In 2015, Andersson and a group of twelve other researchers published results on a study of D-Cycloserine for OCD outcomes, both alone and in interaction with antidepressants. The 12 week study showed that DCS did not significantly augment the effects of cognitive behavioral therapy when used alone. However there was a slight positive interaction in the group receiving concurrent treatment with antidepressants. [25]

Toxicity Reviews:

Due to D-Cycloserine’s previous use as a medication, there is a good availability of data pertaining to its toxicity in both humans and animals. 

In 1997, a case was presented of D-Cycloserine-induced Stevens-Johnson syndrome in an AIDS patient with multidrug resistant tuberculosis (MDR-TB). The syndrome resolved after treatment with DCS was discontinued. [26] In another case, a patient exhibited symptoms of lichenoid drug eruption (LDE). [27]  Patients receiving D-Cycloserine as a medication have exhibited symptoms of vitamin B12 deficiency, folic acid deficiency, megaloblastic anemia, and sideroblastic anemia. [28]

The chemical is associated with a low rate of serum aminotransferase elevations, although it is not considered to be hepatotoxic. [29]

Animal Studies:

Due to a.) the abundance of clinical trials relating to the effects of d-Cycloserine in human participants and b.) the primary focus of research for the chemical being on human-related diseases, biochemical pathways, and clinical outcomes; we have elected to exclude animal research from this compound summary. For a comprehensive list of studies using D-Cycloserine on animals, please refer to the PubMed database and select ‘Other animals’ under the ‘species’ filter.

References:

  • [1] Stammer CH, McKinney JD. (1955). Cycloserine. III. A Schiff Base and Its Reactions, J. Am. Chem. Soc., 77, 2346 
  • [2] El-Obeid HA, Al-Badr AA. (1989). Chapter 57- Analytical Profile of D-Cycloserine, In book: Analytical Profiles of Drug Substances, volume 18, Chapter: Analytical Profile of D-Cycloserine, Publisher: Academic Press, New York, Editors: K. Florey, pp.567-597
  • [3] Cycloserine (Code C47466), National Cancer Institute Thesaurus, Cancer.gov, Available online from https://www.cancer.gov/publications/dictionaries/cancer-drug/def/d-cycloserine [Accessed July 7, 2018] 
  • [4] McEvoy GK, ed. AHFS Drug Information. (2007). Cycloserine. American Society of Health-System Pharmacists; 2007:548-50.
  • [5] Kucers A, Crowe S, Grayson ML et al, eds. (1997). The use of antibiotics. A clinical review of antibacterial, antifungal, and antiviral drugs. 5th ed. Jordan Hill, Oxford: Butterworth-Heinemann; pp. 1228-30.
  • [6] WHO Model List of Essential Medicines, 19th List, April 2015, Available online from www.who.int/medicines/publications/essentialmedicines/en/ [Accessed Jul 19, 2018]
  • [7] Watson GB, Bolanowski MA, Baganoff MP, Deppeler CL, Lanthorn TH. (1990). D-cycloserine acts as a partial agonist at the glycine modulatory site of the NMDA receptor expressed in Xenopus oocytes, Brain Res, 510(1):158-60.
  • [8] Hansen KB, Ogden KK, Traynelis SF. (2012). Subunit-selective allosteric inhibition of glycine binding to NMDA receptors, J Neurosci, 32(18): 6197–6208.
  • [9] Goff DC. (2012). D-Cycloserine: An Evolving Role in Learning and Neuroplasticity in Schizophrenia, Schizophr Bull. 2012 Sep; 38(5): 936–941.
  • [10] Portero-Tresserra M, Cristóbal-Narváez P, Martí-Nicolovius M, Guillazo-Blanch G, Vale-Martínez A. (2013). D-cycloserine in Prelimbic Cortex Reverses Scopolamine-Induced Deficits in Olfactory Memory in Rats, PLoS One, 8(8): e70584.
  • [11] Ohno M, Watanabe S. (1996). D-cycloserine, a glycine site agonist, reverses working memory failure by hippocampal muscarinic receptor blockade in rats, Eur J Pharmacol, 318(2-3):267-71.
  • [12] Wlaz P, Roliński Z, Czuczwar SJ. (2005). Influence of D-Cycloserine on the Anticonvulsant Activity of Phenytoin and Carbamazepine Against Electroconvulsions in Mice, Epilepsia, 37(7). 
  • [13] Zhu M, Nix DE, Adam RD, Childs JM, Peloquin CA. (2001). Pharmacokinetics of cycloserine under fasting conditions and with high-fat meal, orange juice, and antacids, Pharmacotherapy, 21(8):891-7
  • [14] Musson DG, Maglietto SM, Hwang SS, Gravellese D, Bayne WF. (1987). Simultaneous Quantification of Cycloserine and Its Prodrug Acetylacetonylcycloserine in Plasma and Urine by High-Performance Liquid Chromatography Using Ultraviolet Absorbance and Fluorescence After Post-Column Derivatization, J Chromatogr, 414 (1), 121-129.
  • [15] Jones LR. Colorimetric Determination of Cycloserine, New Antibiotic. Anal. Chem, 28(1), pp 39–41. 
  • [16] Sulkowsk ML, Geller DA, Lewin AB, Murphy TK, Mittelman A, Brown A, Storch EA. (2014). The Future of D-Cycloserine and Other Cognitive Modifiers in Obsessive-Compulsive and Related Disorders, Curr Psychiatry Rev, 10(4): 317–324.
  • [17] Zareifopoulos N, Panayiotakopoulos G. (2017). Neuropsychiatric Effects of Antimicrobial Agents, Clin Drug Investig. 2017 May;37(5):423-437
  • [18] Mataix-Cols D, et al. (2017). D-Cycloserine Augmentation of Exposure-Based Cognitive Behavior Therapy for Anxiety, Obsessive-Compulsive, and Posttraumatic Stress Disorders: A Systematic Review and Meta-analysis of Inliidual Participant Data. JAMA Psychiatry, 1;74(5):501-510.
  • [19] Goff DC. (2017). D-cycloserine in Schizophrenia: New Strategies for Improving Clinical Outcomes by Enhancing Plasticity, Curr Neuropharmacol, 15(1):21-34.
  • [20] Schade S, Paulus W. (2016). D-Cycloserine in Neuropsychiatric Diseases: A Systematic Review. Int J Neuropsychopharmacol, 19(4): pyv102.
  • [21] Heresco-Levy U, Gelfin G, Bloch B, Levin R, Edelman S, Javitt DC, Kremer I. (2013) A randomized add-on trial of high-dose D-cycloserine for treatment-resistant depression. Int J Neuropsychopharmacol, 16(3):501-6.
  • [22] Wink LK, et al. (2017). d-Cycloserine enhances durability of social skills training in autism spectrum disorder, Mol Autism, 8:2
  • [23] Forsyth JK, Bachman P, Mathalon DH, Roach BJ, Asarnow RF. (2015). Augmenting NMDA receptor signaling boosts experience-dependent neuroplasticity in the adult human brain, Proc Natl Acad Sci USA, 112(50):15331-6
  • [24] Scholl J, Günthner J, Kolling N, Favaron E, Rushworth MF, Harmer CJ, Reinecke A. (2014). A role beyond learning for NMDA receptors in reward-based decision-making-a pharmacological study using d-cycloserine, Neuropsychopharmacology, 39(12):2900-9.
  • [25] Andersson E, et al. (2015). D-Cycloserine vs Placebo as Adjunct to Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder and Interaction With Antidepressants: A Randomized Clinical Trial, JAMA Psychiatry, 72(7):659-67.
  • [26] Akula SK, Aruna AS, Johnson JE, Anderson DS. (1997). Cycloserine-induced Stevens-Johnson syndrome in an AIDS patient with multidrug-resistant tuberculosis, Int J Tuberc Lung Dis, 1(2):187-90.
  • [27] Kim J, Park S, Jung CM, Oh CW, Kwon JW. (2017). A Case of Cycloserine-Induced Lichenoid Drug Eruption Supported by the Lymphocyte Transformation Test, Allergy Asthma Immunol Res, 9(3):281–284.
  • [28] Cycloserine. (2018). AHFS Monographs, Drugs.com, Available online from https://www.drugs.com/monograph/cycloserine.html [ Accessed July 7, 2018]
  • [29] Cycloserine. (2018). Drug Record, LiverTox, National Library of Medicine, Available online from https://livertox.nih.gov/Cycloserine.htm [Accessed July 7, 2018]

Precaution and Disclaimer:

This Material is Sold For Research Use Only. Terms of Sale Apply. Not for Human Consumption, nor Medical, Veterinary, or Household Uses.

[D-Cycloserine Q2 2017] D-Cycloserine.17020804.pdf