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| D-cycloserine |
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| CHEBI:40009 |
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| D-cycloserine |
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| A 4-amino-1,2-oxazolidin-3-one that has R configuration. It is an antibiotic produced by Streptomyces garyphalus or S. orchidaceus and is used as part of a multi-drug regimen for the treatment of tuberculosis when resistance to, or toxicity from, primary drugs has developed. An analogue of D-alanine, it interferes with bacterial cell wall synthesis in the cytoplasm by competitive inhibition of L-alanine racemase (which forms D-alanine from L-alanine) and D-alanine—D-alanine ligase (which incorporates D-alanine into the pentapeptide required for peptidoglycan formation and bacterial cell wall synthesis). |
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This entity has been manually annotated by the ChEBI Team.
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CHEBI:4030
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| ChemicalBook:CB9138759, eMolecules:496004, Selleckchem:D-Cycloserine, ZINC000034676245 |
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more structures >>
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| Cycloserine, sold under the brand name Seromycin, is a GABA transaminase inhibitor and an antibiotic, used to treat tuberculosis. Specifically it is used, along with other antituberculosis medications, for active drug resistant tuberculosis. It is given by mouth.
Common side effects include allergic reactions, seizures, sleepiness, unsteadiness, and numbness. It is not recommended in people who have kidney failure, epilepsy, depression, or are alcoholics. It is unclear if use during pregnancy is safe for the baby. Cycloserine is similar in structure to the amino acid D-alanine and works by interfering with the formation of the bacteria's cell wall.
Cycloserine was discovered in 1954 from a type of Streptomyces. It is on the World Health Organization's List of Essential Medicines. |
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Read full article at Wikipedia
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| InChI=1S/C3H6N2O2/c4-2-1-7-5-3(2)6/h2H,1,4H2,(H,5,6)/t2-/m1/s1 |
| DYDCUQKUCUHJBH-UWTATZPHSA-N |
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Bronsted base
A molecular entity capable of accepting a hydron from a donor (Bronsted acid).
(via organic amino compound )
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antimetabolite
A substance which is structurally similar to a metabolite but which competes with it or replaces it, and so prevents or reduces its normal utilization.
metabolite
Any intermediate or product resulting from metabolism. The term 'metabolite' subsumes the classes commonly known as primary and secondary metabolites.
NMDA receptor agonist
An excitatory amino acid agonist which binds to NMDA receptors and triggers a response.
antitubercular agent
A substance that kills or slows the growth of Mycobacterium tuberculosis and is used in the treatment of tuberculosis.
antimicrobial agent
A substance that kills or slows the growth of microorganisms, including bacteria, viruses, fungi and protozoans.
(via heterocyclic antibiotic )
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NMDA receptor agonist
An excitatory amino acid agonist which binds to NMDA receptors and triggers a response.
antiinfective agent
A substance used in the prophylaxis or therapy of infectious diseases.
antitubercular agent
A substance that kills or slows the growth of Mycobacterium tuberculosis and is used in the treatment of tuberculosis.
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View more via ChEBI Ontology
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(4R)-4-aminoisoxazolidin-3-one
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cicloserina
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ChemIDplus
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cycloserine
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ChemIDplus
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cyclosérine
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WHO MedNet
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cycloserinum
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ChemIDplus
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(+)-4-amino-3-isoxazolidinone
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ChemIDplus
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(+)-cycloserine
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ChEBI
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(R)-4-AMINO-ISOXAZOLIDIN-3-ONE
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PDBeChem
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α-Cycloserine
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NIST Chemistry WebBook
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cyclo-D-serine
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ChemIDplus
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D-(+)-cycloserine
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ChEBI
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D-4-amino-3-isoxazolidinone
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ChemIDplus
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D-4-amino-3-isoxazolidone
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ChemIDplus
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D-Cycloserine
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ChemIDplus
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D-Cycloserine
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KEGG COMPOUND
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DCS
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ChemIDplus
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orientomycin
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ChemIDplus
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PA 94
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ChemIDplus
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PA-94
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ChemIDplus
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Ro-1-9213
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ChemIDplus
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68-41-7
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CAS Registry Number
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NIST Chemistry WebBook
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68-41-7
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CAS Registry Number
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ChemIDplus
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80798
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Reaxys Registry Number
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Reaxys
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Halaby A, Haddad R, Naja W (2015)
Non-Antidepressant Treatment of Social Anxiety Disorder: A Review.
Current clinical pharmacology 10, 126-130 [PubMed:23438729]
[show Abstract]
Social anxiety disorder is a debilitating mental illness with eventually serious comorbidities such as major depression and alcohol or substance abuse and dependence. Those comorbidities are much more common when social phobia is left neglected and untreated. It is characterized by excessive fears to one or most social situations (circumscribed versus generalized type). Social phobia has its onset typically in childhood or early adolescence and it is associated with significant functional impairment. Although cognitive behavioral therapy and the selective serotonin reuptake inhibitors are considered the mainstay treatment of this disorder, other psychotropic agents can be of value in the management of this condition. This review discusses the efficacy of beta-bockers, benzodiazepines, anticonvulsants, D-cycloserine, buspirone and atypical antipsychotics in the treatment of social anxiety disorder. | Hofmann SG, Fang A, Gutner CA (2014)
Cognitive enhancers for the treatment of anxiety disorders.
Restorative neurology and neuroscience 32, 183-195 [PubMed:23542909]
[show Abstract]
Traditional treatments for anxiety disorders include cognitive-behavioral therapy and anxiolytic medications. Although these treatments are more effective than placebo, there is still considerable room for further improvement. Unfortunately, combining these different modalities is generally not substantially better than monotherapies. Recently, researchers have turned their attention toward translating preclinical research on the neural circuitry underlying fear extinction to clinical applications for the treatment of anxiety disorders with the goal to augment the learning process during exposure-based procedures with cognitive enhancers. This review examines d-cycloserine, cortisol, catecholamines, yohimbine, oxytocin, modafinil, as well as nutrients and botanicals as agents to augment treatment for anxiety disorders. D-cycloserine shows the most empirical support. Other promising agents include cortisol, catecholamines, yohimbine, and possibly oxytocin. Less support comes from studies that examined nutrients and botanicals, such as caffeine, nicotine, and omega-3 fatty acid. Limitations of the exiting literature and future research directions are discussed. | Burket JA, Benson AD, Tang AH, Deutsch SI (2013)
D-Cycloserine improves sociability in the BTBR T+ Itpr3tf/J mouse model of autism spectrum disorders with altered Ras/Raf/ERK1/2 signaling.
Brain research bulletin 96, 62-70 [PubMed:23685206]
[show Abstract]
The genetically inbred BTBR T+ Itpr3tf/J (BTBR) mouse is a proposed model of autism spectrum disorders (ASDs). Similar to several syndromic forms of ASDs, mTOR activity may be enhanced in this mouse strain as a result of increased Ras signaling. Recently, D-cycloserine, a partial glycineB site agonist that targets the NMDA receptor, was shown to improve the sociability of the Balb/c mouse strain, another proposed genetically inbred model of ASDs. NMDA receptor activation is an important regulator of mTOR signaling activity. Given the ability of D-cycloserine to improve the sociability of the Balb/c mouse strain and the regulatory role of the NMDA receptor in mTOR signaling, we wondered if D-cycloserine would improve the impaired sociability of the BTBR mouse strain. D-Cycloserine (320 mg/kg, ip) improved measures of sociability in a standard sociability paradigm and spontaneous grooming that emerged during social interaction with an ICR stimulus mouse in the BTBR strain; however, similar effects were observed in the Swiss Webster comparator strain, raising questions about their strain-selectivity. Importantly, the profile of D-cycloserine's effects on both measures of sociability and stereotypies is consistent with that of a desired medication for ASDs; specifically, a desired medication would not improve sociability at the expense of worsening stereotypic behaviors or vice versa. | Leslie JC, Norwood K (2013)
Facilitation of extinction and re-extinction of operant behavior in mice by chlordiazepoxide and D-cycloserine.
Neurobiology of learning and memory 102, 1-6 [PubMed:23416058]
[show Abstract]
The aim was to compare operant extinction with re-extinction following re-acquisition and to investigate neuropharmacological mechanisms through administration of drugs potentiating GABAergic or glutamatergic systems. Groups of C57Bl/6 mice were trained to lever press for food on a fixed ratio schedule, then extinguished with or without pre-session chlordiazepoxide or post-session d-cycloserine administration (15mg/kg in each case), then retrained to lever press for food, then re-extinguished with or without pre-session chlordiazepoxide or post-session d-cycloserine. Under vehicle injections, extinction and re-extinction curves were indistinguishable, but drug treatments showed that there was less resistance to extinction in the re-extinction phase. Chlordiazepoxide facilitated extinction and re-extinction, with an earlier effect during re-extinction. d-Cycloserine also facilitated extinction and re-extinction, with some evidence of an earlier effect during re-extinction. These results replicate and extend earlier findings with operant extinction, but differ from some previous reports of d-cycloserine on re-extinction of Pavlovian conditioned fear. Implications for accounts of the similarities and differences between neural mechanisms of extinction following either Pavlovian or operant conditioning, and applications of these findings, are discussed. | Ren J, Li X, Zhang X, Li M, Wang Y, Ma Y (2013)
The effects of intra-hippocampal microinfusion of D-cycloserine on fear extinction, and the expression of NMDA receptor subunit NR2B and neurogenesis in the hippocampus in rats.
Progress in neuro-psychopharmacology & biological psychiatry 44, 257-264 [PubMed:23523746]
[show Abstract]
Pharmacological and behavior interventions for inhibiting fear and anxiety are important in the treatment of different types of anxiety disorder. Fear extinction, as a novel form of associative learning, is the most extensively studied models to understand the neural mechanisms of fear-related and anxiety disorders. One of the possible mechanisms of neural plasticity in extinction learning may depend on activation of NMDA receptors in the amygdale; however, the role played by the hippocampus in extinction remains largely unclear. In the present study, using a fear conditioning paradigm, we repeatedly microinfused D-cycloserine, a partial agonist of NMDA receptor, into the hippocampus and investigated the effects of repeated infusions of DCS on extinction behavior and protein levels of NMDA receptor subunit NR2B. We also examined the effects of DCS on neurogenesis in adult rat hippocampus. Our results showed that the administration of DCS facilitated the acquisition and retrieval of extinction memory, and enhanced the expression of NR2B protein in the dentate gyrus, CA1 and CA3 of the hippocampus. We also found that repeated microinfusions of DCS increased proliferation of newly born cells in the hippocampus. These findings suggest that neural plasticity mediated by NMDA receptors in the hippocampus is involved in the enhancement of acquisition and retrieval of extinction memory. | Price KL, Baker NL, McRae-Clark AL, Saladin ME, Desantis SM, Santa Ana EJ, Brady KT (2013)
A randomized, placebo-controlled laboratory study of the effects of D-cycloserine on craving in cocaine-dependent individuals.
Psychopharmacology 226, 739-746 [PubMed:22234379]
[show Abstract]
RationaleD-Cycloserine (DCS), a partial glutamate N-methyl-D-aspartate (NMDA) receptor agonist, enhances extinction of conditioned fear responding; preliminary data suggest that it may facilitate extinction of drug cue reactivity.ObjectiveThis study investigates DCS effects on cocaine cue craving and drug use in cocaine-dependent subjects.MethodsThirty-two subjects were randomly assigned to receive (1) DCS only, (2) DCS before sessions 1 and 3, placebo (PBO) before session 2, or (3) PBO only 15-min before each of 3 1-h cocaine cue exposure sessions conducted 1 day apart. Craving ratings were obtained before, during, and after sessions. Drug use and cue-induced craving were assessed 1 week after the last cue session.ResultsRepeated presentation of cocaine cues resulted in decreased craving both within and between sessions. DCS did not facilitate extinction learning and may have enhanced craving. The group that received three doses of DCS had significantly higher craving than the PBO group at the baseline ratings taken before sessions 2 and 3, as well as significantly higher cue-induced craving at follow-up. The group that received two doses of DCS did not differ from the PBO group. There were no group differences in postextinction cocaine use.ConclusionsThe reduction of cocaine cue reactivity in the PBO group suggests that the study procedures were sufficient to produce extinction. Under these conditions, DCS did not facilitate extinction and may have enhanced craving. Further studies of glutamatergic agents and extinction in cocaine dependence should include consideration of procedural variables that could have a major impact on study outcomes. | 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.
The international journal of neuropsychopharmacology 16, 501-506 [PubMed:23174090]
[show Abstract]
Antagonism of N-methyl-D-aspartate glutamatergic receptors (NMDAR) may represent an effective antidepressant mechanism. D-cycloserine (DCS) is a partial agonist at the NMDAR-associated glycine modulatory site that at high doses acts as a functional NMDAR antagonist. Twenty-six treatment-resistant major depressive disorder patients participated in a double blind, placebo-controlled, 6-wk parallel group trial with a gradually titrated high dose (1000 mg/d) of DCS added to their antidepressant medication. DCS treatment was well tolerated, had no psychotomimetic effects and led to improvement in depression symptoms as measured by Hamilton Depression Rating Scale (HAMD; p = 0.005) and Beck Depression Inventory (p = 0.046). Of the 13 subjects treated with DCS, 54% had a ≥ 50% HAMD score reduction vs. 15% of the 13 patients randomized to placebo (p = 0.039). A significant (p = 0.043) treatment× pre-treatment glycine serum levels interaction was registered. These findings indicate that NMDAR glycine site antagonism may be a cost-effective target for development of mechanistically novel antidepressants. Larger-sized DCS trials are warranted. | Rodebaugh TL, Lenze EJ (2013)
Lessons learned from D-cycloserine: the promise and limits of drug facilitation of exposure therapy.
The Journal of clinical psychiatry 74, 415-416 [PubMed:23656850] | Hofmann SG, Sawyer AT, Asnaani A (2012)
D-cycloserine as an augmentation strategy for cognitive behavioral therapy for anxiety disorders: an update.
Current pharmaceutical design 18, 5659-5662 [PubMed:22632472]
[show Abstract]
Cognitive behavioral therapy (CBT) has been shown to be an effective intervention for anxiety disorders. However, despite its proven efficacy, some patients fail to respond to an adequate course of treatment. In attempts to improve the efficacy of CBT, researchers have augmented the core learning processes of the intervention with d-cycloserine (DCS), an N-Methyl-D-Aspartate partial agonist. This article reviews the current literature on DCS as an augmentation strategy for CBT for anxiety disorders. We will describe the memory enhancing properties of DCS, review findings from randomized controlled studies of DCS in anxious populations and discuss mechanism, dosing and timing issues. | Goff DC (2012)
D-cycloserine: an evolving role in learning and neuroplasticity in schizophrenia.
Schizophrenia bulletin 38, 936-941 [PubMed:22368237]
[show Abstract]
As a partial agonist at the glycine site of the NMDA receptor, D-cycloserine (DCS) has been viewed as lacking potency to fully test the NMDA receptor hypofunction theory of schizophrenia. However, findings of full agonist activity at a subset of NMDA receptors that may have particular relevance to schizophrenia, plus a growing body of evidence demonstrating enhancement of learning and neuroplasticity in animal models, suggest novel therapeutic strategies with DCS in schizophrenia. Preliminary studies with once-weekly administration have supported this potential new role for DCS in schizophrenia by demonstrating benefit for negative symptoms, memory consolidation, and facilitation of cognitive behavioral therapy for delusions. | Pawlak CR, Chen FS, Wu FY, Ho YJ (2012)
Potential of D-cycloserine in the treatment of behavioral and neuroinflammatory disorders in Parkinson's disease and studies that need to be performed before clinical trials.
The Kaohsiung journal of medical sciences 28, 407-417 [PubMed:22892161]
[show Abstract]
Hyperactivation of glutamatergic N-methyl-D-aspartate (NMDA) receptors has been implicated in the excitotoxicity and pathophysiology of Parkinson's disease (PD). NMDA receptor blockers have been used clinically to treat dementia, but their efficacy is controversial. Modulation of NMDA receptors might improve neuroinflammation and cognitive deficits in PD. D-cycloserine (DCS), a partial agonist binding to the glycine binding site of NMDA receptors, has been demonstrated to improve cognitive function in primates and rodents. Our previous study showed that DCS can reduce motor, emotional, and cognitive dysfunctions, as well as neuroinflammation and neurodegeneration in a PD animal model and may therefore have potential for the treatment of neuroinflammation and cognitive dysfunction in patients with PD. In addition, increased expression of cyclooxygenase type-2 (COX-2) has been observed in dopaminergic neurons and activated microglia in the brain of both PD patients and PD animal models. COX-2 inhibitors can suppress activation of microglia and protect dopaminergic neurons from degeneration. Thus, a combination of DCS and COX-2 inhibitors might prove useful in suppressing neuroinflammation and cognitive deficits in PD. | Davenport RA, Houpt TA (2009)
D-cycloserine enhances short-delay, but not long-delay, conditioned taste aversion learning in rats.
Pharmacology, biochemistry, and behavior 91, 596-603 [PubMed:18930757]
[show Abstract]
NMDA receptors have been implicated in conditioned taste aversion (CTA), a form of associative learning with the unique temporal characteristic of associating taste and toxic stimuli across very long delays. d-cycloserine (DCS), an NMDA receptor agonist, has been shown to enhance short-delay CTA learning. Here we examined the interaction of DCS with varying temporal parameters of CTA. DCS (15 mg/kg) administered prior to the pairing of 0.125% saccharin and LiCl (38 mM, 12 ml/kg) enhanced CTA when there was a short delay between the taste-toxin pairing (10 min), but not when there was a long delay (45 min). DCS activity remained at effective levels over the long delay, because DCS administered 60 min prior to a short-delay pairing enhanced CTA. The interaction of DCS with the delay between taste stimulus onset and LiCl injection was investigated by administering DCS and then 5 min access to saccharin 45 min prior to a short-delay pairing of saccharin and LiCl. DCS failed to enhance CTA in rats pre-exposed to saccharin, even with a short delay between the second saccharin exposure and LiCl injection. These results suggest that DCS enhancement of CTA is dependent on mechanisms underlying gustatory processing during long-delay taste-toxin associations. | Vervliet B (2008)
Learning and memory in conditioned fear extinction: effects of D-cycloserine.
Acta psychologica 127, 601-613 [PubMed:17707326]
[show Abstract]
This review addresses the effects of the cognitive enhancer D-cycloserine (DCS) on the memory processes that occur in conditioned fear extinction, which is the experimental model for exposure techniques to reduce clinical anxiety. All reported rat studies show an enhanced fear extinction effect when DCS is administered acutely before or shortly after extinction training. DCS also promotes the generalization of this fear extinction effect. In addition, DCS reduces some forms of relapse (reduced reinstatement, reduced spontaneous recovery), but not others (contextual renewal, rapid reacquisition). It is argued that this pattern of results is best explained by assuming that DCS promotes extinction learning to the background context, resulting in enhanced contextual inhibition. Four human studies have produced mixed results, but some methodological issues complicate the reported failures. It is concluded that DCS is a promising tool as an adjunct to extinction techniques in exposure treatment, but that more pre-clinical and clinical research is needed to fully characterize its behavioral consequences. | Rothbaum BO (2008)
Critical parameters for D-cycloserine enhancement of cognitive-behaviorial therapy for obsessive-compulsive disorder.
The American journal of psychiatry 165, 293-296 [PubMed:18316423] | (2008)
Cycloserine.
Tuberculosis (Edinburgh, Scotland) 88, 100-101 [PubMed:18486041] | Laake K, Oeksengaard AR (2002)
D-cycloserine for Alzheimer's disease.
The Cochrane database of systematic reviewsCD003153 [PubMed:12076471]
[show Abstract]
BackgroundEvidence supports a role for the NMDA receptors in learning and memory. These can be modulated by the antibiotic D-cycloserine in such a way that the effect of the excitatory transmitter substance glutamate is enhanced. A study on healthy subjects pretreated with scopolamine to mimic Alzheimer's disease showed a positive effect of D-cycloserine at low doses.ObjectivesTo assess the efficacy and safety of D-cycloserine in patients with Alzheimer's disease.Search strategyThe trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 14 June 2001 using the terms: cycloserine, D-cycloserine, Alzheimer*.Selection criteriaRandomized, double-blinded and unconfounded trials comparing D-cycloserine with a control treatment.Data collection and analysisTwo larger and two smaller randomized controlled trials were identified. The clinical global impression scale was used in all studies and was a primary outcome measure.Main resultsIt was not possible to extract the results from the first phases of the two crossover studies and therefore the meta-analyses are based on the two parallel group 6-month studies. There was no indication of a positive effect favouring D-cycloserine for the numbers showing improvement at 6 months as assessed by the Clinical Global Impression for any dose. The number of withdrawals for any reason before end of treatment at 6 months was significantly in favour of placebo (fewer withdrawals) compared with D-cycloserine for dose levels of 30 mg/day (OR 2.94, 95% CI 1.52, 5.70) and 100 mg/day (OR 3.23, 95% CI 1.67, 6.25). There was no significant difference between treatment, (2, 10, 30, 100, or 200 mg/day) and placebo for the number of withdrawals due to adverse events by six months.Reviewer's conclusionsThe lack of a positive effect of D-cycloserine on cognitive outcomes in controlled clinical trials with statistical power high enough to detect a clinically meaningful effect means that D-cycloserine has no place in the treatment of patients with Alzheimer's disease. | Lambert MP, Neuhaus FC (1972)
Mechanism of D-cycloserine action: alanine racemase from Escherichia coli W.
Journal of bacteriology 110, 978-987 [PubMed:4555420]
[show Abstract]
The antibiotic d-cycloserine is an effective inhibitor of alanine racemase. The lack of inhibition by l-cycloserine of alanine racemase from Staphylococcus aureus led Roze and Strominger to formulate the cycloserine hypothesis. This hypothesis states that d-cycloserine has the conformation required of the substrates on the enzyme surface and that l-cycloserine cannot have this conformation. Alanine racemase from Escherichia coli W has been examined to establish whether these observations are a general feature of all alanine racemases. The enzyme (molecular weight = 95,000) has Michaelis-Menten constants of 4.6 x 10(-4)m and 9.7 x 10(-4)m for d- and l-alanine, respectively. The ratio of V(max) in the d- to l-direction is 2.3. The equilibrium constant calculated from the Haldane relationship is 1.11 +/- 0.15. Both d- and l-cycloserine are competitive inhibitors with constants (K(i)) of 6.5 x 10(-4)m and 2.1 x 10(-3)m, respectively. The ratio of K(m)d-alanine to K(i)d-cycloserine is 0.71, and the ratio of K(m)l-alanine to K(i)l-cycloserine is 0.46. Since l-cycloserine is an effective inhibitor, it is concluded that the cycloserine hypothesis does not apply to the enzyme from E. coli W. | Protivinsky R (1971)
Cycloserine.
Antibiotics and chemotherapy 17, 87-94 [PubMed:5006234] |
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