Metabolomics in pharmacology - a delve into the novel field of pharmacometabolomics

Mussap, Michele; Loddo, Cristina; Fanni, Claudia; Fanos, Vassilios

doi:10.1080/17512433.2020.1713750

Cited by 27 publications

(17 citation statements)

References 204 publications

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“…When compared with post-exposure results, this SNP was strongly associated with levels of inosine and guanosine [180]. The examples presented above [142,144,146,179,180] as well as other available literature [36,175,178] demonstrate the importance of pharmacometabolomics in drug design studies. Combined with other approaches, e.g., pharmacogenomic, pharmacometabolomics can greatly contribute to our understanding of individual differences in responses to drug treatment and thus directly aid us in the development of new generations of drugs.…”

Section: Losartanmentioning

confidence: 82%

“…Metabolomics provides a snapshot of the metabolite dynamics, and is a powerful tool when investigating numerous perturbations in biological systems, including pathophysiological events, environmental stimuli, and genetic modifications [31][32][33][34]. Moreover, metabolomics investigates every perturbation in metabolite compositions and/or concentrations, and it has already been applied in different fields such as biomedicine, environmental science, nutrition and diet studies, microbiology, and drug toxicology, as well as marine and plant sciences [35][36][37][38][39].…”

Section: Metabolomicsmentioning

confidence: 99%

“…Samples are usually collected before, during, and after the treatment, and can be further divided by type of response from an individual (e.g., mostly positive, mostly negative, or intermediate) [175,178]. After obtaining data from a set of samples using various techniques adapted to the particular type [36,175,178], a database for each individual is created, with metabolites detected and identified before and after the treatment [178]. Lastly, a statistical analysis is applied to obtain information ranging from differences that can distinguish good and poor responders prior to the treatment, to changes in metabolites due to drug application that can be correlated with response phenotypes and assumptions of pathways connected to variants of response [178].…”

Section: Safety Biomarkermentioning

confidence: 99%

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Pharmacometabolomics: A New Horizon in Personalized Medicine

Emwas¹,

Szczepski

McKay³

et al. 2021

Metabolomics - Methodology and Applications in Medical Sciences and Life Sciences

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Pharmacology is the predominant first-line treatment for most pathologies. However, various factors, such as genetics, gender, diet, and health status, significantly influence the efficacy of drugs in different patients, sometimes with fatal consequences. Personalized diagnosis substantially improves treatment efficacy but requires a more comprehensive process for health assessment. Pharmacometabolomics combines metabolomic, genomic, transcriptomic and proteomic approaches and therefore offers data that other analytical methods cannot provide. In this way, pharmacometabolomics more accurately guides medical professionals in predicting an individual’s response to selected drugs. In this chapter, we discuss the potentials and the advantages of metabolomics approaches for designing innovative and personalized drug treatments.

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Section: Losartanmentioning

confidence: 82%

Section: Metabolomicsmentioning

confidence: 99%

Section: Safety Biomarkermentioning

confidence: 99%

See 1 more Smart Citation

Pharmacometabolomics: A New Horizon in Personalized Medicine

Emwas¹,

Szczepski

McKay³

et al. 2021

Metabolomics - Methodology and Applications in Medical Sciences and Life Sciences

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“…Both the TCA cycle and amino acid metabolism are linked. There is a reduction in ATP production due to inhibition of the TCA cycle induced by high altitude hypoxia, leading to the utilization of branched-chain amino acids as energy resource 2 , 18 , 22 .…”

Section: Discussionmentioning

confidence: 99%

Urinary metabolic modulation in human participants residing in Siachen: a 1H NMR metabolomics approach

Gandhi

Chinnadurai

Bhadra

et al. 2022

Sci Rep

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The main physiological challenge in high altitude environment is hypoxia which affects the aerobic metabolism reducing the energy supply. These changes may further progress toward extreme environment-related diseases. These are further reflected in changes in small molecular weight metabolites and metabolic pathways. In the present study, metabolic changes due to chronic environmental hypoxia were assessed using 1H NMR metabolomics by analysing the urinary metabolic profile of 70 people at sea level and 40 people at Siachen camp (3700 m) for 1 year. Multivariate statistical analysis was carried out, and PLSDA detected 15 metabolites based on VIP score > 1. ROC analysis detected cis-aconitate, Nicotinamide Mononucleotide, Tyrosine, Choline and Creatinine metabolites with a high range of sensitivity and specificity. Pathway analysis revealed 16 pathways impact > 0.05, and phenylalanine tyrosine and tryptophan biosynthesis was the most prominent altered pathway indicating metabolic remodelling to meet the energy requirements. TCA cycle, Glycine serine and Threonine metabolism, Glutathione metabolism and Cysteine alterations were other metabolic pathways affected during long-term high-altitude hypoxia exposure. Present findings will help unlock a new dimension for the potential application of NMR metabolomics to address extreme environment-related health problems, early detection and developing strategies to combat high altitude hypoxia.

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“…The combination of group and time/dose metabolomics data, as well as behavioural data, makes the current data set unique. This is particularly true within the addiction field, where metabolomics approaches have yet to gain much traction (Ghanbari & Sumner, 2018;Mussap, Loddo, Fanni, & Fanos, 2020). Given this unique combination of group, time/dose, and behavioural data, a relatively novel data statistical approach needed to be developed.…”

Section: Introductionmentioning

confidence: 99%

Effect of repeated MDMA exposure on rat brain and behaviour

Wetering¹

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<p>Rationale. ±3,4-Methylenedioxymethamphetamine (MDMA; ‘ecstasy’) is a popular recreational drug of abuse. Like other drugs of abuse, a proportion of users develop symptoms that are characteristic of a Substance Use Disorder (SUD). The behavioural and neurobiological consequences of repeated misuse of MDMA are not well understood, however. Objectives. The purpose of the present thesis was to investigate behaviourally relevant neuroadaptations that develop with repeated MDMA exposure in laboratory rats. Methods. First, the effect of chronic, long-access (6 hour) self-administration of MDMA on the accumulation of the transcription factor, ΔFosB, in the nucleus accumbens (core, shell), dorsal striatum (dorsomedial, dorsolateral, ventromedial, ventrolateral), prefrontal cortex (anterior cingulate, prelimbic, infralimbic, orbitofrontal), amygdala (central, basolateral), ventral tegmental area (anterior, posterior), and raphe (dorsal, median) was measured using immunohistochemistry. Second, the behavioural relevance of these findings was determined by examining the effect of bi-lateral intra-striatal (nucleus accumbens, dorsomedial striatum, dorsolateral striatum) microinjections of MDMA (200 μg/1 μL/side) on the expression of behavioural sensitisation following two days of withdrawal from a regimen of repeated, systemic MDMA exposure (10 mg/kg/day, i.p., for 5 days). Third, a procedure was developed to examine neurochemical correlates of sensitised MDMA-produced behaviour (0, 5, 10 mg/kg, i.p.) following the same regimen of repeated MDMA exposure. Samples were collected from the medial striatum using in vivo microdialysis and the extracellular concentrations of serotonin, dopamine, MDMA, and their metabolites were quantified using liquid chromatography coupled with quadrupole time-of-flight (Q-TOF) mass spectrometry. Lastly, a unique untargeted metabolomics procedure was developed to further analyse these microdialysis samples and to identify novel or unexpected metabolites that were relevant to the sensitised behavioural response produced by MDMA. Results. MDMA self-administration produced region-dependant increases in ΔFosB. Significant increases in ΔFosB were observed in the nucleus accumbens core, the medial areas of the dorsal striatum, as well as all areas of the prefrontal cortex and amygdala. Small, but significant increases were also observed in the dorsal raphe. Increases were observed in the nucleus accumbens shell and the posterior tail of the ventral tegmental area, but these increases were not significant following statistical correction for multiple comparisons. Acute exposure to MDMA increased locomotor activity only when the drug was infused into the nucleus accumbens. Following repeated systemic exposure, behavioural sensitisation was expressed when MDMA was infused into both the nucleus accumbens or the dorsomedial striatum, but not the dorsolateral striatum. Analysis of microdialysates from the medial striatum indicated that behavioural sensitisation was accompanied by small increases in baseline levels of extracellular serotonin and decreased MDMA-produced increases in serotonin, but these changes were not statistically significant. Behavioural sensitisation was also accompanied by increased extracellular concentrations of dopamine at baseline and following acute MDMA exposure, but these data were not statistically analysed due to small sample sizes. MDMA-produced extracellular concentrations of MDMA did not change with repeated exposure. Untargeted metabolomics revealed potential changes in MDMA and dopamine metabolism that might be relevant to the sensitised behavioural response. Conclusions. The findings of the current research suggest that repeated MDMA exposure results in many of the same neuroadaptations that result from repeated exposure to other drugs of abuse. These included increased ΔFosB expression in many brain regions that are relevant to addiction, such as the nucleus accumbens, dorsal striatum, and prefrontal cortex. Dopaminergic mechanisms also appeared to be influenced and were associated with sensitised MDMA-produced behaviour. Surprisingly, serotonergic mechanisms were not significantly impacted by repeated MDMA exposure under the current conditions. Some of the procedures developed in this thesis are unique and may be of value for future research investigating the neurochemical underpinnings of addictive behaviour or other disease states.</p>

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Metabolomics in pharmacology - a delve into the novel field of pharmacometabolomics

Cited by 27 publications

References 204 publications

Pharmacometabolomics: A New Horizon in Personalized Medicine

Pharmacometabolomics: A New Horizon in Personalized Medicine

Urinary metabolic modulation in human participants residing in Siachen: a 1H NMR metabolomics approach

Effect of repeated MDMA exposure on rat brain and behaviour

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