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Toxics
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Toxicity of Central Nervous System (CNS) Modulators
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Toxicity of Central Nervous System (CNS) Modulators

A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Drugs Toxicity".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 3026

Special Issue Editors

Prof. Dr. Youssef Sari

E-Mail Website
Guest Editor
Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Toledo, OH 43614, USA
Interests: the neuropharmacology and toxicology of drugs of abuse in the central nervous and peripheral systems; drug discovery
Special Issues, Collections and Topics in MDPI journals
Dr. Fawaz Alasmari

E-Mail Website
Guest Editor
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Interests: the toxicological and pharmacological effects of drugs of abuse in the brain
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The main focus of this Special Issue is to identify the toxicological effects of drugs that are considered modulators and can be used to treat diseases and disorders associated with the central nervous system. The Special Issue also focuses on the toxicological effects of drugs of abuse that affect the CNS. These drugs of abuse include ethanol, cannabis, psychostimulants (e.g., methamphetamine, cathinone, cocaine and others), opioids, and nicotine, as well as other synthetic drugs (heroin, balt salt, etc.) and other illicit drugs. This Special Issue seeks research articles that mainly investigate the toxicological effects of CNS modulators in acute and chronic paradigms. CNS modulators include approved medications and illicit drugs.

We invite investigators from different research areas to present their studies on the toxicological effects of CNS modulators which can be illicit and non-illicit drugs that have modulatory effects in the brain. We also encourage investigators to submit review articles or method research articles centered around the toxicity of CNS modulators.

Prof. Dr. Youssef Sari
Dr. Fawaz Alasmari
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • toxicity
  • opioids
  • substances of abuse
  • illicit drugs
  • methamphetamine
  • cannabis
  • drugs of abuse
  • psychostimulants
  • nicotine

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Further information on MDPI's Special Issue polices can be found here.

Published Papers (3 papers)

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Research

20 pages, 4171 KiB  
Article
Neuroinflammation and Neurometabolomic Profiling in Fentanyl Overdose Mouse Model Treated with Novel β-Lactam, MC-100093, and Ceftriaxone
by Mohammed S. Alasmari, Fawaz Alasmari, Shakir D. Alsharari, Abdullah F. Alasmari, Nemat Ali, Syed Rizwan Ahamad, Abdullah M. Alghamdi, Aban A. Kadi, Alaa M. Hammad, Yousif S. Mohamed Ali, Wayne E. Childers, Magid Abou-Gharbia and Youssef Sari
Toxics 2024, 12(8), 604; https://doi.org/10.3390/toxics12080604 - 19 Aug 2024
Viewed by 885
Abstract
Opioid-related deaths are attributed to overdoses, and fentanyl overdose has been on the rise in many parts of the world, including the USA. Glutamate transporter 1 (GLT-1) has been identified as a therapeutic target in several preclinical models of substance use disorders, and [...] Read more.
Opioid-related deaths are attributed to overdoses, and fentanyl overdose has been on the rise in many parts of the world, including the USA. Glutamate transporter 1 (GLT-1) has been identified as a therapeutic target in several preclinical models of substance use disorders, and β-lactams effectively enhance its expression and function. In the current study, we characterized the metabolomic profile of the nucleus accumbens (NAc) in fentanyl-overdose mouse models, and we evaluated the protective effects of the functional enhancement of GLT-1 using β-lactams, ceftriaxone, and MC-100093. BALB/c mice were divided into four groups: control, fentanyl, fentanyl/ceftriaxone, and fentanyl/MC-100093. While the control group was intraperitoneally (i.p.) injected with normal saline simultaneously with other groups, all fentanyl groups were i.p. injected with 1 mg/kg of fentanyl as an overdose after habituation with four repetitive non-consecutive moderate doses (0.05 mg/kg) of fentanyl for a period of seven days. MC-100093 (50 mg/kg) and ceftriaxone (200 mg/kg) were i.p. injected from days 5 to 9. Gas chromatography–mass spectrometry (GC-MS) was used for metabolomics, and Western blotting was performed to determine the expression of target proteins. Y-maze spontaneous alternation performance and the open field activity monitoring system were used to measure behavioral manifestations. Fentanyl overdose altered the abundance of about 30 metabolites, reduced the expression of GLT-1, and induced the expression of inflammatory mediators IL-6 and TLR-4 in the NAc. MC-100093 and ceftriaxone attenuated the effects of fentanyl-induced downregulation of GLT-1 and upregulation of IL-6; however, only ceftriaxone attenuated fentanyl-induced upregulation of TRL4 expression. Both of the β-lactams attenuated the effects of fentanyl overdose on locomotor activities but did not induce significant changes in the overall metabolomic profile. Our findings revealed that the exposure to a high dose of fentanyl causes alterations in key metabolic pathways in the NAc. Pretreatment with ceftriaxone and MC-100093 normalized fentanyl-induced downregulation of GLT-1 expression with subsequent attenuation of neuroinflammation as well as the hyperactivity, indicating that β-lactams may be promising drugs for treating fentanyl use disorder. Full article
(This article belongs to the Special Issue Toxicity of Central Nervous System (CNS) Modulators)
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17 pages, 3057 KiB  
Article
Green Tea Polyphenol Nanoparticles Reduce Anxiety Caused by Tobacco Smoking Withdrawal in Rats by Suppressing Neuroinflammation
by Alaa M. Hammad, Lujain F. Alzaghari, Malek Alfaraj, Vanessa Lux and Suhair Sunoqrot
Toxics 2024, 12(8), 598; https://doi.org/10.3390/toxics12080598 - 18 Aug 2024
Viewed by 854
Abstract
Repeated exposure to tobacco smoke causes neuroinflammation and neuroplasticity, which correlates with smoking withdrawal-induced anxiety. The purpose of this study was to investigate the anticipated involvement of antioxidant-rich nanoparticles (NPs) prepared by oxidation-triggered polymerization of green tea catechins in impacting these effects in [...] Read more.
Repeated exposure to tobacco smoke causes neuroinflammation and neuroplasticity, which correlates with smoking withdrawal-induced anxiety. The purpose of this study was to investigate the anticipated involvement of antioxidant-rich nanoparticles (NPs) prepared by oxidation-triggered polymerization of green tea catechins in impacting these effects in a rat model of tobacco smoke exposure. Exposure to tobacco smoke was carried out for 2 h a day, 5 days a week, for a total of 36 days. Weekly behavioral tests were conducted prior to recommencing the exposure. Following a 20-day exposure period, rats were administered either distilled water or green tea (GT) NPs (20 mg/kg, orally) for an additional 16 days. Our findings revealed that tobacco smoke exposure induced anxiety-like behavior indicative of withdrawal, and this effect was alleviated by GT NPs. Tobacco smoke exposure caused a marked increase in the relative mRNA and protein expression of nuclear factor-kappa B (NF-κB) and reduced the relative mRNA and protein expression of brain-derived neurotrophic factor (BDNF) in the hippocampus (HIP) and hypothalamus (HYP) brain subregions. The intervention of GT NPs effectively inhibited these effects. Our findings demonstrate the potent protective role of GT NPs in reducing withdrawal-induced anxiety-like behavior, neuroinflammation, and neuroplasticity triggered by tobacco smoke exposure. Full article
(This article belongs to the Special Issue Toxicity of Central Nervous System (CNS) Modulators)
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24 pages, 3219 KiB  
Article
Predictors of Serotonin Syndrome in Acute Poisoning with 5-Hydroxytryptamine Modulators
by Asmaa F. Sharif, Mubarak Nasir M. Almulhim, Hadi Mohamed A. Almosabeh, Mohammed Essam A. Alshammasy, Ali Mohammed A. Aljeshi, Taher Mohammed A. Mufti, Shahd AlNasser, Khalid A. Al-Mulhim and Yousef A. AlMubarak
Toxics 2024, 12(8), 550; https://doi.org/10.3390/toxics12080550 - 30 Jul 2024
Viewed by 1011
Abstract
5-Hydroxytryptamine (5-HT) modulators are commonly prescribed medications with potentially life-threatening outcomes, particularly serotonin syndrome (SS). Early prediction of SS is critical not only to avoid lethal drug combinations but also to initiate appropriate treatment. The present work aimed to recognize the significant predictors [...] Read more.
5-Hydroxytryptamine (5-HT) modulators are commonly prescribed medications with potentially life-threatening outcomes, particularly serotonin syndrome (SS). Early prediction of SS is critical not only to avoid lethal drug combinations but also to initiate appropriate treatment. The present work aimed to recognize the significant predictors of SS through a retrospective cross-sectional study that was conducted among patients exposed to an overdose of 5-HT modulators and admitted to a poison control center where 112 patients were enrolled. Of them, 21 patients were diagnosed with SS, and 66.7% of patients with SS were exposed to long-term co-ingestion. There was a noticeable surge in SS between April and May, and 52.4% of patients who suffered from SS were admitted after suicidal exposure (p < 0.05). Patients with SS showed severe presentation indicated by high-grade poison severity scores (PSS) and low Glasgow coma scales (GCS). PSS was a significant predictor of SS with an area under the curve of 0.879. PCO2, pulse, GCS, HCO3, and erythrocytic count were other significant predictors of SS. Combinations of serotonergic agents increase the likelihood of developing SS. Clinicians should be vigilant when prescribing a combination of serotonergic therapy, particularly for patients on illicit sympathomimetic and over-the-counter medications like dextromethorphan. Full article
(This article belongs to the Special Issue Toxicity of Central Nervous System (CNS) Modulators)
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