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Molecular Research on the Drug Toxicity

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: 20 May 2025 | Viewed by 3984

Special Issue Editor


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Guest Editor
National Centre on Addiction and Doping, National Institute of Health, Rome, Italy
Interests: forensic toxicology; analytical chemistry; drugs of abuse; new psychoactive substances; clinical toxicology; clinical chemistry; analytical pharmacology; drugs addiction
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Besides having therapeutic and beneficial outcomes, drug intake may produce an array of adverse effects, limiting the therapeutic efficacy of constituent substances and defining the width of the therapeutic window. Although pharmaceutical drug toxicity has been thoroughly assessed according to the rigorous protocols that have been carried out during development processes, several undesirable effects may unpredictably occur due to chronic drug consumption or other uncontrollable factors, such as drug target and metabolic enzyme polymorphisms. Moreover, the toxicity resulting from polydrug exposure is often difficult to define due to the number of possible combinations in experimental settings. In case of psychotropic drug diversion, these unexpected events may result in severe intoxication, with potentially fatal consequences.

Indeed, psychotropic drugs and drugs of abuse toxicity are directly experimented with by users at first usage, with unforeseen ramifications. In particular, the toxicity from new psychoactive substances (NPSs) represents the most challenging aspect of this ever-growing phenomenon. This is a result of the lack of pharmacological information on these substances at their release on the illegal market. Moreover, adulteration may further complicate this issue.

In this context, this Special Issue aims to collect original research papers, letters to the editor, review articles, perspective articles and brief communications to contribute to the development of valid knowledge on the molecular mechanisms of drug toxicity.

Suggested topics include the following:

  • Studies on drugs and NPS metabolism.
  • Studies and updated reviews on drugs, drugs of abuse and NPS-related toxicity.
  • Development and validation of analytical methods for the identification and quantification of drug markers in conventional and non-conventional biological matrices.
  • Studies on the molecular mechanisms of drug toxicity.
  • Case reports on drugs and their adulterants' toxicity.

Dr. Annagiulia Di Trana
Guest Editor

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Keywords

  • drug toxicity
  • new psychoactive substances
  • toxicology
  • drug metabolism
  • drug intoxication

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Published Papers (2 papers)

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Research

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25 pages, 5196 KiB  
Article
Molecular Aspects of the Interactions between Selected Benzodiazepines and Common Adulterants/Diluents: Forensic Application of Theoretical Chemistry Methods
by Jelica Džodić, Milica Marković, Dejan Milenković and Dušan Dimić
Int. J. Mol. Sci. 2024, 25(18), 10087; https://doi.org/10.3390/ijms251810087 - 19 Sep 2024
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Abstract
Benzodiazepines are frequently encountered in crime scenes, often mixed with adulterants and diluents, complicating their analysis. This study investigates the interactions between two benzodiazepines, lorazepam (LOR) and alprazolam (ALP), with common adulterants/diluents (paracetamol, caffeine, glucose, and lactose) using infrared (IR) spectroscopy and quantum [...] Read more.
Benzodiazepines are frequently encountered in crime scenes, often mixed with adulterants and diluents, complicating their analysis. This study investigates the interactions between two benzodiazepines, lorazepam (LOR) and alprazolam (ALP), with common adulterants/diluents (paracetamol, caffeine, glucose, and lactose) using infrared (IR) spectroscopy and quantum chemical methods. The crystallographic structures of LOR and ALP were optimized using several functionals (B3LYP, B3LYP-D3BJ, B3PW91, CAM-B3LYP, M05-2X, and M06-2X) combined with the 6-311++G(d,p) basis set. M05-2X was the most accurate when comparing experimental and theoretical bond lengths and angles. Vibrational and 13C NMR spectra were calculated to validate the functional’s applicability. The differences between LOR’s experimental and theoretical IR spectra were attributed to intramolecular interactions between LOR monomers, examined through density functional theory (DFT) optimization and quantum theory of atoms in molecules (QTAIM) analysis. Molecular dynamics simulations modeled benzodiazepine–adulterant/diluent systems, predicting the most stable structures, which were further analyzed using QTAIM. The strongest interactions and their effects on IR spectra were identified. Comparisons between experimental and theoretical spectra confirmed spectral changes due to interactions. This study demonstrates the potential of quantum chemical methods in analyzing complex mixtures, elucidating spectral changes, and assessing the structural stability of benzodiazepines in forensic samples. Full article
(This article belongs to the Special Issue Molecular Research on the Drug Toxicity)
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Review

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20 pages, 889 KiB  
Review
New Psychoactive Substances Toxicity: A Systematic Review of Acute and Chronic Psychiatric Effects
by Beldisa Taflaj, Nunzia La Maida, Roberta Tittarelli, Annagiulia Di Trana and Ilaria D’Acquarica
Int. J. Mol. Sci. 2024, 25(17), 9484; https://doi.org/10.3390/ijms25179484 - 31 Aug 2024
Cited by 2 | Viewed by 2123
Abstract
New psychoactive substances (NPSs) are a heterogenous group of psychotropic molecules and diverted pharmaceutical drugs sold worldwide as legal substitutes for controlled drugs. The psychiatric consequences of NPS use are relatively unknown, although evidence of related psychotic symptoms has been described in the [...] Read more.
New psychoactive substances (NPSs) are a heterogenous group of psychotropic molecules and diverted pharmaceutical drugs sold worldwide as legal substitutes for controlled drugs. The psychiatric consequences of NPS use are relatively unknown, although evidence of related psychotic symptoms has been described in the literature. We sought to summarize the available evidence on NPS-related psychiatric disorders, to facilitate the interpretation of the molecular mechanism underlying their specific pathologies. A literature search of Scopus, PubMed and Google Scholar was conducted including studies published between 2013 and 2024, in which a correlation between NPS consumption and psychiatric symptoms was reported. Furthermore, the short- and long-term psychopathological effects were included. The literature search resulted in 109 NPS-related intoxication cases in which acute or chronic psychiatric symptoms were reported, mostly related to synthetic cannabinoids, followed by synthetic cathinones, hallucinogens, natural NPSs and stimulants. The most common acute symptoms were hallucinations, aggressiveness, and psychotic and bizarre behavior, related to the molecular disbalance of neurotransmitters in the central nervous systems, with different mechanisms. The lack of clear diagnostic criteria and toxicological analyses has resulted in crucial complications in psychiatric diagnoses related to NPS intoxication. Hence, the implementation of toxicological screening procedures in emergency rooms, including the main NPS classes, should support the diagnosis of acute intoxication and its proper therapeutic treatment. Finally, proper follow-up should be implemented to assess the chronic sequelae. Full article
(This article belongs to the Special Issue Molecular Research on the Drug Toxicity)
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