Cycloserine

• CAS: 68-41-7
• Catalog Number: ACM68417
• Category: Main Products
• Molecular Weight: 102.09
• Molecular Formula: C3H6N2O2
• Synonyms: D-cycloserine
• Melting Point: 147 °C
• Appearance: White to Off-White powder

Case Study

Effects of D-cycloserine on extinction studies

Davis, Michael, et al. Biological psychiatry 60.4 (2006): 369-375.

The combination of benzodiazepines or serotonin reuptake inhibitors with behavioral therapy for many anxiety disorders generally results in only modest gains. It is suggested that drug therapy, which is not designed to treat anxiety symptoms but is instead aimed at improving the learning that occurs during exposure therapy, may actually improve the effectiveness of exposure therapy. This idea is based on animal work showing that the partial N-methyl-D-aspartate (NMDA) agonist D-cycloserine (DCS) facilitates extinction of fear when given before or shortly after exposure to a fear cue, reduces the return of fear typically seen with stress that follows extinction training, and leads to generalized extinction (extinction is not typically caused by the erasure of the original fear memory but rather represents a new form of learning that acts to inhibit or suppress the original fear memory) where DCS combined with exposure to one fear cue leads to extinction to another cue that was previously paired with the same aversive event. Studies have shown that DCS facilitates exposure therapy for acrophobia in a well-controlled virtual reality environment.
The rats were initially trained with two different cues (i.e., a light and a tone), each accompanied by a loud aversive noise. The next day, some rats received two (2 h apart) extinction training sessions with a visual cue. After the second extinction training session, some rats were immediately injected with DCS, while others were injected with saline. Other rats were injected with saline or DCS on the same day but were not given extinction training. 24 h later, the light and tone were presented separately (test order was counterbalanced) and freezing levels were measured. Results obtained using a visual conditioned stimulus (CS) replicated earlier findings, in which shock was the aversive unconditioned stimulus (US). DCS-treated rats showed generalized extinction of fear. This effect was not observed in rats injected with saline after extinction training or in rats injected with DCS but not given extinction training.

Pharmacokinetic studies of d-cycloserine in multidrug-resistant tuberculosis

Deshpande, Devyani, et al. Clinical Infectious Diseases 67.suppl_3 (2018): S308-S316.

D-cycloserine is used to treat multidrug-resistant tuberculosis. Its efficacy, role in combination therapy, and optimal clinical dose are unknown, and data on the distribution of minimum inhibitory concentrations (MICs) for d-cycloserine are scarce. Studies A systematic search was performed to identify pharmacokinetic and pharmacodynamic studies with d-cycloserine. A new HFS-TB experiment was performed. Cyloserine killed 6.3 log colony forming units (CFU)/mL of extracellular bacilli over 28 days. Efficacy was driven by the percentage of time (%T) that the concentration was sustained above the MIC, with %T = 30% (target exposure) achieving 1.0 logCFU/mL killing. The tentative epidemiologic cutoff value for the Sensititre MYCOTB assay is 64 mg/L. In the MCE, 750 mg twice daily achieved target exposure in the lung cavity in 92% of patients, while 500 mg twice daily achieved target exposure in 85% of patients with meningitis. At the recommended dose, the proposed MCE-derived clinical susceptibility cutoff is 64 mg/L.
Minimum inhibitory concentrations (MICs) of d-cycloserine for Mtb H37Ra and H37Rv were determined using 4 methods: Sensititre MYCOTB plates, large broth dilution, and 1% indirect proportional method using Middlebrook 7H10 and MGIT. For the latter 3 methods, concentrations of 0, 0.5, 1, 2, 4, 8, 16, 32, and 64 mg/L were tested. Next, the microbial killing effects of different concentrations of d -cycloserine were examined against extracellular Mtb in vitro and intracellular Mtb in infected THP-1 cells activated with 100 nM phorbol 12-myristate 13-acetate in 12-well plates for 72 h and coincubated with the drugs.

D-cycloserine consolidates neuroplasticity in the human motor cortex

Nitsche, Michael A., et al. Neuropsychopharmacology 29.8 (2004): 1573-1578.

D-cycloserine is a partial N-methyl-aspartate (NMDA) agonist that has been shown to improve cognitive function in humans. However, the neurophysiological basis of this effect is still unclear to date. The effects of this drug on the long-term sequelae of changes in motor cortical excitability produced by transcranial direct current (tDCS), as revealed by motor evoked potentials induced by transcranial magnetic stimulation, were investigated. Anodal tDCS enhances motor cortical excitability, whereas cathodal tDCS reduces it. Both effects appear to be NMDA receptor-dependent. D-cycloserine selectively enhances the duration of anodal tDCS-induced enhancement of motor cortical excitability. -D-cycloserine alone does not modulate excitability. The ability of this drug to consolidate the enhancement of neuronal excitability, most likely through stabilization of NMDA receptors, which may be a neurophysiological derivative of learning processes, makes it an interesting substance for improving cognitive function.
Subjects were orally administered 100 mg of D-cycloserine or an equivalent placebo (PLC) drug 2 h before the start of each experiment. D-cycloserine induced stable plasma levels 2 h after oral intake. D-cycloserine was administered immediately after baseline measurements of intracortical and corticospinal excitability, and a second measurement was performed 2 h after intake. To avoid cumulative drug effects, each experimental session was separated by at least 1 week. Subjects were blinded to their respective pharmacological conditions. To detect current-driven changes in excitability, motor evoked potentials (MEPs) were recorded from the right ADM after stimulation of its motor cortical representation field by single-pulse TMS. Signals were amplified and filtered with a time constant of 10 ms and a low-pass filter of 2.5 kHz. Signals were then digitized at an analog-to-digital rate of 5 kHz and further relayed to a laboratory computer using the software collection and conventional averaging software.

D-cycloserine for extinction of conditioned freezing

Ledgerwood, Lana, Rick Richardson, and Jacquelyn Cranney. Behavioral neuroscience 117.2 (2003): 341.

The study tested the prediction that D-cycloserine (DCS), a partial N-methyl-aspartate agonist, would facilitate extinction of conditioned freezing in male Sprague-Dawley rats. Rats received 5 pairs of light shocks (conditioning). The next day, rats received 6 presentations of light alone (extinction training). 24 hours later, rats received 1 presentation of light alone (test). Subcutaneous administration of DCS before or after extinction training significantly enhanced extinction, and the dose-response curve for this effect was linear. Increasing delays in DCS administration after extinction training resulted in a linear decrease in the facilitation effect. The effects of systemic administration were replicated by basolateral amygdala infusions. These results suggest that DCS facilitates extinction of conditioned freezing by acting on consolidation processes that are mediated in part by the basolateral amygdala.
DCS at various doses (2.5, 5.0, 10.0, and 15.0 mg/kg) was freshly dissolved in sterile isotonic saline (0.9% wt/vol) and injected subcutaneously in a volume of 1.0 ml/kg. Control rats were injected subcutaneously with saline (0.9% wt/vol) in a volume of 1.0 ml/kg. Drug doses were selected based on the results of other behavioral studies. Intraamygdala infusion. Immediately after extinction training, either DCS (10 g dissolved in 0.5 L saline) or 0.5 L saline was infused over 1 min. Rats were handled for 2 min daily for at least 3 consecutive days and assigned to weight-matched groups before the start of each experiment. The behavioral procedures for Experiments 3-5 included a contextual preexposure phase, a fear conditioning phase, an extinction training session, and a posttest. For Experiments 1 and 2, there was no preexposure phase.

Custom Q&A

What is the molecular formula of D-cycloserine?

The molecular formula of D-cycloserine is C3H6N2O2.

What is the molecular weight of D-cycloserine?

The molecular weight of D-cycloserine is 102.09 g/mol.

What is the IUPAC name of D-cycloserine?

The IUPAC name of D-cycloserine is (4R)-4-amino-1,2-oxazolidin-3-one.

What is the InChIKey of D-cycloserine?

The InChIKey of D-cycloserine is DYDCUQKUCUHJBH-UWTATZPHSA-N.

What is the canonical SMILES representation of D-cycloserine?

The canonical SMILES representation of D-cycloserine is C1C(C(=O)NO1)N.

What is the CAS number of D-cycloserine?

The CAS number of D-cycloserine is 68-41-7.

What is the European Community (EC) Number of D-cycloserine?

The European Community (EC) Number of D-cycloserine is 200-688-4.

What is the UNII of D-cycloserine?

The UNII of D-cycloserine is 95IK5KI84Z.

What is the ChEMBL ID of D-cycloserine?

The ChEMBL ID of D-cycloserine is CHEMBL771.

What is the KEGG ID of D-cycloserine?

The KEGG ID of D-cycloserine is C08057.