These neuroactive molecules and metabolites, consisting of neurotransmitters, such as glutamate, or neuromodulators,
such as acetylcholine (ACh), can be detected by appropriate techniques in the extracellular fluid of the brain. Many of these neurotransmitters also exist in blood, but their concentrations are different from those in the brain because Inhibitors,research,lifescience,medical of the differential permeability of the blood-brain barrier (BBB) and of differences in absorption mechanism, synthesis, and metabolism. In recent years, the accurate measurement of neurotransmitter concentrations in an accessible matrix has provided an opportunity to use those concentrations as preclinical and clinical biomarkers of CNS penetration
and target engagement [101,102]. ACh, one of the neurotransmitters released by cholinergic neurons in the CNS, plays an important role in sleep regulation, learning and memory, cognitive function, and Inhibitors,research,lifescience,medical the pathology of neurological disorders, such as Parkinson’s disease, Alzheimer’s disease, and schizophrenia. Therefore, an analytical technique that enables the simultaneous determination of biomarkers of both cholinergic and histaminergic systems in an accessible biological matrix, such as CSF, would be a useful research tool to better understand the underlying mechanisms and implications Inhibitors,research,lifescience,medical for therapeutic Inhibitors,research,lifescience,medical interventions. Diao et al. developed a simple and sensitive method for the simultaneous analysis of three catecholamines: dopamine, epinephrine, and norepinephrine, in urine, by CE, coupled with in-column fiber-optic light-emitting diode-induced fluorescence detection (ICFO-LED-IFD) . CE-ICFO-LED-IFD has
been successfully applied to the analysis of catecholamines in human urine samples, offering good accuracy and satisfactory recovery. Meanwhile, Zhang et al. developed and validated a UPLC-MS/MS method to simultaneously quantify neurochemical concentrations in rat CSF. They used a HILIC column to separate highly polar Inhibitors,research,lifescience,medical compounds . Li et al. determined neurochemicals in brain and blood selleck chem Vorinostat samples of non-human primates in parallel by dual microdialysis, and subsequently conducted analysis by a Entinostat direct capillary HILIC-MS-based method . 4.4. Tricarboxylic Acid Cycle Studies of the metabolites in the tricarboxylic acid (TCA) cycle are considered to be essential for metabolomics analysis. The main metabolites in the TCA cycle are di- and tricarboxylic (TCA) acids. The TCA cycle has three primary functions: (i) to provide biosynthetic intermediates, (ii) to generate reducing potential, and (iii) to directly produce a small amount of ATP. The availability of biosynthetic intermediates affects the availability of amino acids and nucleic acids. Mammalian cells depend on the metabolism of glucose and glutamine for proliferation.