D-cycloserine is an antibiotic which targets sequential bacterial cell wall peptidoglycan biosynthesis enzymes: alanine racemase and D-alanine:D-alanine ligase[3]. Furthermore, in an in vivo infection model with silkworms, combined treatment with vancomycin and D-cycloserine exhibited therapeutic effects, whereas treatment with each compound alone did not. These findings suggest that combined treatment with vancomycin and D-cycloserine could be therapeutically effective against infectious diseases caused by VRSA (vancomycin-highly resistant S. aureus)[4]. D-cycloserine is used to treat multidrug-resistant tuberculosis. Cyloserine killed 6.3 log10 colony-forming units (CFU)/mL extracellular bacilli over 28 days[5]. D-Cycloserine (CYC), a partial N-methyl-D-aspartate (NMDA) agonist, has been shown to improve cognitive functions in humans. D-CYC alone did not modulate excitability. The potency of this drug to consolidate neuronal excitability enhancements, most probably by stabilizing the strengthening of NMDA receptors[6]. D-Cycloserine in low-dose therapy is safe, but there is still a need for new drugs with higher specificity to the different N-methyl-D-aspartate-receptor subunits[7].
D-Cycloserine/D-(+)-环丝氨酸 细胞实验
Cell Line
Concentration
Treated Time
Description
References
CA1 pyramidal neurons in hippocampal brain slices
20 µM
To investigate the modulation of hippocampal synaptic plasticity by DCS, it was found that DCS enhances NMDAR-dependent long-term potentiation (LTP) and long-term depression (LTD)
Transl Psychiatry. 2024 Jan 9;14(1):18
Mycobacterium tuberculosis H37Rv
64 µg/mL
4 weeks
Determine the spontaneous mutation rate of D-cycloserine
Nat Commun. 2019 Sep 13;10(1):4177
Mycobacterium tuberculosis H37Rv
100 µg/mL
4 weeks
Determine the spontaneous mutation rate of D-cycloserine
Nat Commun. 2019 Sep 13;10(1):4177
E. coli DdlB (EcDdlB)
5 mM DCS
Investigate the mechanism of D-cycloserine inhibition of D-alanine:D-alanine ligase, revealing that D-cycloserine inhibits the enzyme via a phosphorylated form (DCSP).
Nat Commun. 2017 Dec 5;8(1):1939
D-Cycloserine/D-(+)-环丝氨酸 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Sprague-Dawley rats
Morphine-dependent rat model
Intraperitoneal injection
15 mg/kg
Single dose, administered immediately prior to extinction training
D-cycloserine facilitates extinction of morphine withdrawal-associated place aversion
Biol Psychiatry. 2010 Jan 1;67(1):85-7
Children
Autism Spectrum Disorder
Oral
50 mg
Once weekly for 10 weeks
To assess the efficacy and adverse effects of D-cycloserine plus social skills training compared to placebo plus social skills training on social and communication skills in children with ASD. Results showed little to no difference between D-cycloserine and placebo in social interaction, communication, and stereotyped patterns of behavior at one week and 12 weeks post-treatment.
Cochrane Database Syst Rev. 2021 Feb 14;2(2):CD013457
Rats
Alcohol drinking model
Intraperitoneal injection
10 mg/kg
Single dose, 15–20 min before
To study the effect of DCS on aversion-resistant alcohol intake, results showed DCS significantly reduced aversion-resistant alcohol intake but had no effect on quinine-free alcohol intake
Neuropsychopharmacology. 2015 Sep;40(10):2357-67
Sprague-Dawley rats
Spared nerve injury (SNI) and cisplatin-induced neuropathy
Oral
3, 10, or 30 mg/kg
Twice daily for 14 days
DCS treatment resulted in a dose-dependent reduction in mechanical sensitivity of the injured limb, with effects persisting for weeks after cessation of treatment. Re-exposure to DCS further enhanced antinociceptive behavior. Repeated oral DCS also reduced cancer chemotherapy drug-induced neuropathic pain behavior.
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