Disease relevance of cycloserine

• We have shown that it is harder to inhibit the catalytic activity of ALR from D-cycloserine (DCS)-producing Streptomyces lavendulae than that from Escherichia coli by DCS [1].
• In the present study, we cloned a gene, designated bpsA, which encodes a single module type non-ribosomal peptide synthetase (NRPS) from a d-cycloserine (DCS)-producing Streptomyces lavendulae ATCC11924 [2].
• In agreement with recently published crystallographic data, we also observe similar changes in backbone torsions corresponding to the hinge region between the two lobes for the partial agonist, d-cycloserine [3].
• Chlamydia growth is inhibited by D-cycloserine (DCS) and in vitro analysis provided evidence for the chlamydial MurC-Ddl as the target for DCS sensitivity [4].
• Significant synergy was shown to occur between pleurocidin and D-cycloserine targeting Mycobacterium smegmatis [5].

Psychiatry related information on cycloserine

• Augmentation of exposure therapy with D-cycloserine for social anxiety disorder [6].
• Fear reduction in exposure therapy is similar to extinction learning, and early clinical data with specific phobias suggest that the treatment effects of exposure therapy for SAD may be enhanced with d-cycloserine, an agonist at the glutamatergic N-methyl-d-aspartate receptor [6].
• Improved cognition in Alzheimer's disease with short-term D-cycloserine treatment [7].
• METHOD: Following a 2-week, single-blind placebo lead-in phase, drug-free subjects with autistic disorder were administered three different doses of D-cycloserine during each of three 2-week periods [8].
• Previous administration of D-serine to schizophrenic patients taking nonclozapine antipsychotics improved positive, negative, and cognitive symptoms, whereas the partial agonist D-cycloserine improved negative symptoms of patients taking conventional antipsychotics but worsened symptoms in clozapine-treated patients [9].

High impact information on cycloserine

• Cognitive enhancers as adjuncts to psychotherapy: use of D-cycloserine in phobic individuals to facilitate extinction of fear [10].
• Sensitivity of the cells to exogenous autolysin requires treatment with penicillin or other inhibitors of cell wall synthesis (e.g., D-cycloserine or fosfonomycin) since exogenous autolysin alone has no effect on bacterial growth [11].
• D-Cycloserine is an active site titrant of D-amino acid transaminase [12].
• A transcriptome analysis using microarrays verified that the algD operon undergoes high induction by d-cycloserine [13].
• In addition, a mutation in gene PA3257 (prc), encoding a Prc-like protease, resulted in poor induction of PalgD-cat by d-cycloserine, suggesting that it also plays a role in the response to cell wall stress [13].

Chemical compound and disease context of cycloserine

• Glycine and D-cycloserine did not worsen cognitive test performance and did not induce behavioral symptoms on their own [14].
• We additionally report the L- and D-cycloserine inactivated crystal structures of Bacillus stearothermophilus alanine racemase, which corroborates the spectroscopy via evidence of a 3-hydroxyisoxazole pyridoxamine derivative [15].
• Flavomycin, bacitracin, vancomycin, D-cycloserine, penicillin G, and ampicillin also inhibited formation of radiolabeled peptidoglycan by the E. coli cells [16].
• L-Cycloserine was a more potent inhibitor of the growth of Bacteroides levii than was D-cycloserine, indicating that inhibition of sphingolipid synthesis could be a factor in the growth inhibition [17].
• Temperature-sensitive mutants of Actinobacillus pleuropneumoniae 4074, serotype 1, were isolated after treatment with nitrosoguanidine and enrichment with penicillin and D-cycloserine [18].

Biological context of cycloserine

• Consolidation of human motor cortical neuroplasticity by D-cycloserine [19].
• Homologous recombination of the viaB locus into the chromosome of S. typhi Ty21a was induced by UV irradiation, and Vi-positive recombinants were selected in the presence of D-cycloserine [20].
• D-cycloserine uses an active transport mechanism in the human intestinal cell line Caco 2 [21].
• The selectivity of the reporter strains ranged from generic pathways like protein biosynthesis, cell wall biosynthesis, and fatty acid biosynthesis to compound classes (quinolones and glycopeptides) and individual compounds (rifampin, cycloserine, and clindamycin) [22].
• The effect of inhibitors of ceramide de novo synthesis, fumonisin B1 and cycloserine, on photoreceptor apoptosis was investigated [23].

Anatomical context of cycloserine

• RESULTS: D-Cycloserine at a dose of 50 mg/day produced a significant reduction (mean = 21%, SD = 28%) in negative symptoms and significantly improved reaction time as measured by Sternberg's Item Recognition Paradigm, a test mediated in part by prefrontal cortex [24].
• In the present work, further characterization of the transport of D-cycloserine in the human intestinal cell line Caco 2 has shown that this occurs in the apical-to-basolateral direction by an active mechanism which is energy dependent but only partially sodium dependent [21].
• An increased risk of central nervous system effects with concomitant cycloserine has been reported and seen clinically [25].
• The effect of alanine is observed either in vivo, in rats pretreated with cycloserine to prevent its transamination, or in isolated liver cells under conditions in which its metabolic transformation is fully impeded [26].
• The adjunction of D-cycloserine enhanced c-fos expression only for clozapine in both regions of the forebrain [27].

Associations of cycloserine with other chemical compounds

• The serine racemase activity was partially (64%) inhibited by D-cycloserine, whereas host alanine racemase activity was almost totally inhibited (97%) [28].
• IV glycine and oral D-cycloserine effects on plasma and CSF amino acids in healthy humans [14].
• Behavioral and neuroendocrine effects of the partial NMDA agonist D-cycloserine in healthy subjects [29].
• A pharmacological analysis of this binding site indicates that D-serine (Ki = 0.27 microM), D-alanine (Ki = 1.02 microM), and D-cycloserine (Ki = 2.33 microM) are potent inhibitors of binding, whereas the corresponding L isomers have significantly less activity (Ki = 25.4 microM, 15.9 microM, and greater than 100 microM, respectively) [30].
• In the macrophage cell line assay, CRL8131 produced a synergistic effect on intracellular killing of M. tuberculosis by isoniazid, rifampin, streptomycin, pyrazinamide, thiacetazone, D-cycloserine, ethionamide, amikacin, clindamycin, and p-aminosalicylic acid [31].

Gene context of cycloserine

• We investigated the activation of the early gene form of Homer after acute treatment with typical or atypical antipsychotic drugs alone or with the adjunction of D-cycloserine [27].
• We infused D-cycloserine (DCS), a partial agonist of the glycine site on the NMDA receptor, bilaterally into the amygdala 30 min before extinction training [32].
• The thyrotropin-releasing hormone, D-cycloserine, and acetazolamide for SCA6 may have some efficacy [33].
• In lysine-deprived cells, D-cycloserine treatment caused 41- and 71-fold accumulations of UDP-MurNAc-tripeptide in rel+ and relA strains, respectively [34].
• The straightforward procedure is based on a simple phenotype-genotype relationship, and detects mutations in the single-copy, chromosomal cycA gene, involved in the uptake of D-cycloserine [35].

Analytical, diagnostic and therapeutic context of cycloserine

• METHODS: Seventeen schizophrenia outpatients treated with clozapine were assigned in random order to 6-week trials of D-cycloserine 50 mg/day and placebo in a crossover design separated by a 1 week placebo washout [36].
• D-cycloserine was well tolerated and did not induce side-effects according to the Visual Analog Scales (VAS), the Brief Psychiatric Rating Scale (BPRS) and the Adverse Events Checklist (AEC) & codes [29].
• In cases of severe complications quinolones rather than cycloserine may be given in addition to standard triple antituberculosis drug therapy or if one of these drugs is not tolerated [37].
• All of the 78 strains produced an unidentified indole derivative(s), detected with paradimethylaminocinnamaldehyde reagent, and hydrocinnamic acid, detected by gas-liquid chromatography; all exhibited a high degree of resistance to cycloserine, sulfamethoxazole, and trimethoprim [38].
• The minimum inhibitory concentrations of selected beta-lactam antibiotics and D-cycloserine were identical for the parent and mutant strains at both 30 and 42 degrees C. Both mutants failed to form colonies at 42 degrees C, and both gave rise to spontaneous temperature-resistant revertants [39].

References