-
NanoImpact Jan 2023The terrestrial environment is one of the main recipients of plastic waste. However, limited research has been performed on soil contamination by plastics and even less...
The terrestrial environment is one of the main recipients of plastic waste. However, limited research has been performed on soil contamination by plastics and even less assessing the effects of nanoplastics (NPls). Behind the potential toxicity caused per se, NPls are recognized vectors of other environmental harmful contaminants. Therefore, the main aim of the present study is to understand whether the toxicity of an industrial chemical (bisphenol A - BPA) and a pharmaceutical (diphenhydramine - DPH) changes in the presence of polystyrene NPls to the terrestrial invertebrate Folsomia candida. Assessed endpoints encompassed organismal (reproduction, survival and behavior) and biochemical (neurotransmission and oxidative stress) levels. BPA or DPH, 28 d single exposures (1 to 2000 mg/kg), induce no effect on organisms' survival. In terms of reproduction, the calculated EC50 (concentration that causes 50% of the effect) and determined LOEC (lowest observed effect concentration) were higher than the environmental concentrations, showing that BPA or DPH single exposure may pose no threat to the terrestrial invertebrates. Survival and reproduction effects of BPA or DPH were independent on the presence of NPls. However, for avoidance behavior (48 h exposure), the effects of the tested mixtures (BPA + NPls and DPH + NPls) were dependent on the NPls concentration (at 0.015 mg/kg - interaction: no avoidance; at 600 mg/kg - no interaction: avoidance). Glutathione S-transferase activity increased after 28 d exposure to 100 mg/kg DPH + 0.015 mg/kg NPls (synergism). The increase of lipid peroxidation levels found after the exposure to 0.015 mg/kg NPls (a predicted environmental concentration) was not detected in the mixtures (antagonism). The results showed that the effects of the binary mixtures were dependent on the assessed endpoint and the tested concentrations. The findings of the present study show the ability of NPls to alter the effects of compounds with different natures and mechanisms of toxicity towards soil organisms, showing the importance of environmental risk assessment considering mixtures of contaminants.
Topics: Animals; Diphenhydramine; Microplastics; Soil; Arthropods; Invertebrates
PubMed: 36610661
DOI: 10.1016/j.impact.2023.100450 -
Annals of Internal Medicine Jul 1957
Topics: Apnea; Diphenhydramine; Humans
PubMed: 13435691
DOI: 10.7326/0003-4819-47-1-172 -
British Medical Journal May 1948
Topics: Diphenhydramine; Iridocyclitis
PubMed: 18858445
DOI: 10.1136/bmj.1.4558.955 -
Clinical Pharmacology and Therapeutics Dec 1974
Topics: Adult; Amines; Body Weight; Diphenhydramine; Fluorometry; Half-Life; Humans; Indicators and Reagents
PubMed: 4447663
DOI: 10.1002/cpt19741661066 -
International Journal of Pharmaceutical... 2020The objective of this project was to study the percutaneous absorption of lorazepam, diphenhydramine hydrochloride, and haloperidol from a topical Pluronic lecithin...
The objective of this project was to study the percutaneous absorption of lorazepam, diphenhydramine hydrochloride, and haloperidol from a topical Pluronic lecithin organogel, also known as ABH gel, across the porcine ear skin and verify its suitability for topical application. ABH gel was prepared using lecithin in isopropyl palmitate solution (1:1) as an oil phase and 20% w/v Poloxamer 407 solution as an aqueous phase. The gel was characterized for pH, viscosity, drug content, and thermal behavior. A robust high-performance liquid chromatography method was developed and validated for simultaneous analysis of lorazepam, diphenhydramine hydrochloride, and haloperidol. The percutaneous absorption of lorazepam, diphenhydramine hydrochloride, and haloperidol from ABH gel was carried out using Franz cells across the Strat-M membrane and pig ear skin. The pH of ABH gel was found to be 5.66 ± 0.13. The retention time of diphenhydramine hydrochloride, haloperidol, and lorazepam was found to be 5.2 minutes, 7.8 minutes, and 18.9 minutes, respectively. The ABH gel was found to be stable for up to 30 days. Theoretical steady state plasma concentrations (CSS) of diphenhydramine hydrochloride, haloperidol, and lorazepam calculated from flux values were found to be 1.6 ng/mL, 0.13 ng/mL, and 2.30 ng/mL, respectively. The theoretical CSS of diphenhydramine hydrochloride, haloperidol, and lorazepam were much lower than required therapeutic concentrations for antiemetic activity to relieve chemotherapy-induced nausea and vomiting. From the percutaneous absorption data, it was evident that ABH gel failed to achieve required systemic levels of lorazepam, diphenhydramine hydrochloride, and haloperidol following topical application.
Topics: Animals; Antiemetics; Diphenhydramine; Haloperidol; Lorazepam; Skin Absorption; Swine
PubMed: 32196480
DOI: No ID Found -
Mini Reviews in Medicinal Chemistry Oct 2012In addition to their antihistamine effects, H1-receptor antagonists possess pharmacological properties that are not uniformly distributed among this class of drugs, such...
In addition to their antihistamine effects, H1-receptor antagonists possess pharmacological properties that are not uniformly distributed among this class of drugs, such as anti-inflammatory, anti-allergic and antiplatelet activities. In this paper, Cyclizine (1-benzhydryl-4-methyl-piperazine, I), bromodiphenhydramine (2-[(4-bromophenyl)-phenylmethoxy]-N, N-dimethylethanamine, II) and some of their new piperazine and ethanolamine derivatives (III-VIII) inducing changes in substitution of phenyl and amine moieties were synthesized and their acute and chronic antiinflammatory effects were evaluated by standard pharmacological tests. The results showed that substitution of phenyl by tolyl, anisol and cumene groups in piperazine family could remarkably decrease acute inflammation in these new drugs. Also, substitution of dimethylamine by morpholine group could not decrease this inflammation in new synthesized ethanolamine family. But the results from the cotton pellet-induced granuloma formation in rats showed that none of drugs (I-VIII) were effective to reduce the chronic inflammation.
Topics: Animals; Anti-Inflammatory Agents; Cotton Fiber; Diphenhydramine; Edema; Ethanolamine; Granuloma; Histamine H1 Antagonists; Male; Piperazine; Piperazines; Rats; Rats, Wistar; Receptors, Histamine H1
PubMed: 22876948
DOI: 10.2174/138955712802762013 -
Japanese Journal of Pharmacology Mar 1952
Topics: Animals; Diphenhydramine; Electroencephalography; Humans; Rabbits
PubMed: 14955340
DOI: 10.1254/jjp.1.2_87 -
Regulatory Toxicology and Pharmacology... Jul 2020This work provides case studies for the pharmacokinetic (PK) analog approach, where a physiologically based pharmacokinetic (PBPK) model for a target chemical (has no PK...
This work provides case studies for the pharmacokinetic (PK) analog approach, where a physiologically based pharmacokinetic (PBPK) model for a target chemical (has no PK data) is evaluated using PK data from a source chemical (has existing PK data). A bottom up PBPK modeling approach (using in vitro and in silico inputs) is used to develop human oral PBPK models for caffeine and diphenhydramine. Models are evaluated using in vivo data from structural and functional PK analogs. At the end of the case studies, in vivo PK data for caffeine and diphenhydramine is introduced and both models were able to simulate plasma concentrations which agreed with the in vivo PK data. To further demonstrate that structural analogs can serve as PK analogs, in vitro metabolism and plasma protein binding was compared for a subset of structurally similar ToxCast chemicals and shown to be similar. Next steps for the PK analog approach should focus on evaluating this concept for a broader set of compounds. Using PK analogs for evaluating and establishing confidence in a PBPK model will ensure that PBPK modeling remains a viable option in animal alternative safety assessments.
Topics: Animal Testing Alternatives; Animals; Caffeine; Diphenhydramine; Humans; Models, Biological; Molecular Structure
PubMed: 32387187
DOI: 10.1016/j.yrtph.2020.104667 -
Channels (Austin, Tex.) Jan 2018An established characteristic of neoplastic cells is their metabolic reprogramming, known as the Warburg effect, with greater reliance on energetically less efficient...
Diphenhydramine inhibits voltage-gated proton channels (Hv1) and induces acidification in leukemic Jurkat T cells- New insights into the pro-apoptotic effects of antihistaminic drugs.
An established characteristic of neoplastic cells is their metabolic reprogramming, known as the Warburg effect, with greater reliance on energetically less efficient pathways (such as glycolysis and pentose phosphate shunt) compared with oxidative phosphorylation. This results in an overproduction of acidic species that must be extruded to maintain intracellular homeostasis. We recently described that blocking the proton currents in leukemic cells mediated by Hv1 ion channels triggers a marked intracellular acidification and apoptosis induction. Moreover, histamine H1-receptor antagonists were found to induce apoptosis in tumoral cells but the mechanism is still unclear. By using Jurkat T cells, we now show how diphenhydramine inhibits Hv1 mediated currents, inducing a drop in intracellular pH and cellular viability. This provides evidence of a new target structure responsible of the known pro-apoptotic action of antihistaminic drugs.
Topics: Antineoplastic Agents; Apoptosis; Cell Proliferation; Cell Survival; Diphenhydramine; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Ion Channels; Jurkat Cells; Structure-Activity Relationship
PubMed: 28514187
DOI: 10.1080/19336950.2017.1331799 -
The New England Journal of Medicine Jan 1977
Topics: Adult; Diphenhydramine; Female; Humans; Trismus
PubMed: 830291
DOI: 10.1056/NEJM197701132960223