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Journal of Cardiovascular Pharmacology Mar 2024Amphetamine derivatives are used worldwide legally or illegally and intoxications may be accompanied by cardiac arrhythmias. Here, we tested contractile effects of...
Amphetamine derivatives are used worldwide legally or illegally and intoxications may be accompanied by cardiac arrhythmias. Here, we tested contractile effects of cumulative applied (±)-amphetamine, pseudoephedrine, nor-pseudoephedrine (cathine), and cathinone in electrically stimulated (1 Hz) human right atrial preparations (HAP) and mouse left atrial preparations and in spontaneously beating mouse right atrial preparations. In mouse atrial preparations, amphetamine increased force of contraction and beating rate in a concentration- and time-dependent manner, starting at 1 µM in left atrial preparations to 157.1% ± 3.0% and right atrial preparations to 146.6% ± 9.8% at 10 µM, respectively [mean ± standard error of the mean (SEM); n = 5; P < 0.05]. Pseudoephedrine, cathine, or cathinone alone were ineffective in mouse atrial preparations but after pre-incubation with the phosphodiesterase IV inhibitor rolipram (0.1 µM), a positive inotropic effect was noted (mean ± SEM: pseudoephedrine: 112.3% ± 9.8%; cathine: 109.0% ± 4.3%; cathinone: 138.3% ± 21.2%). The effects of all drugs were greatly attenuated by 10 µM cocaine or 10 µM propranolol treatments. However, In HAP, not only amphetamine (to a mean ± SEM of 208% ± 32%) but also pseudoephedrine (to a mean ± SEM of 287% ± 60%), cathine (to a mean ± SEM of 234% ± 52%), and cathinone (to a mean ± SEM of 217% ± 65%) increased force of contraction without the need of phosphodiesterase inhibition. The contractile effects in HAP were attenuated by 10 µM cocaine and antagonized by 10 µM propranolol. We conclude that amphetamine, pseudoephedrine, cathine, and cathinone act probably via release of noradrenaline from cardiac stores as indirect sympathomimetic agents in mouse and more pronounced in human atrial preparations.
Topics: Humans; Amphetamine; Pseudoephedrine; Propranolol; Cocaine; Myocardial Contraction; Alkaloids; Phenylpropanolamine
PubMed: 38181215
DOI: 10.1097/FJC.0000000000001536 -
Journal of Ethnopharmacology Mar 2024Xingbei Zhike granule (XBZK), a widely prescribed Chinese patent medicine, is known for its efficacy in clearing lung qi, relieving cough and reducing phlegm, as well as...
HEADINGS ETHNOPHARMACOLOGICAL RELEVANCE
Xingbei Zhike granule (XBZK), a widely prescribed Chinese patent medicine, is known for its efficacy in clearing lung qi, relieving cough and reducing phlegm, as well as fever, dry and bitter taste, and irritability. Despite its clinical popularity, comprehensive investigations into its chemical composition, in vivo metabolism, and pharmacokinetic characteristics are limited.
AIM OF THE STUDY
This study investigates the chemical composition, in vivo metabolism, and in vivo dynamics of XBZK to clarify its material basis and pharmacokinetic characteristics.
MATERIALS AND METHODS
Ultra-high performance liquid chromatography with Orbitrap tandem mass spectrometry (UPLC-Orbitrap-MS) was used to determine the chemical composition and in vivo metabolic profile of XBZK. Additionally, UPLC with triple quadrupole mass spectrometry (UPLC-TQ-MS/MS) was performed to quantify its main components and evaluate its in vivo dynamics in rat plasma.
RESULTS
In total, 57 components were identified in XBZK. Furthermore, 40 prototype components and 31 metabolites were detected in various biological matrices of rats, including plasma, tissues, bile, feces, and urine. After administration, the area under the curve (AUC) for ephedrine (Eph), pseudoephedrine (Peph), neotuberostemonine (Neo), amygdalin (Amy), and enoxolone (Eno) exhibited a strong linear relationship with the administered dose (r > 0.9) in all rats. And gender-related differences in the absorption of peiminine (Pmn), peimisine (Pms), and chrysin-7-O-glucuronide (Cog) were notable among rats, with male rats showing a dose-dependent pattern of absorption, while female rats exhibited minimal absorption.
CONCLUSIONS
XBZK contains 57 components, primarily composed of flavonoids, alkaloids, and coumarins. The eight main components were rapidly absorbed and eliminated, with some, such as Eph, Peph, Neo, Amy and Eno, following a linear pharmacokinetic pattern. Furthermore, Pmn, Pms and Cog were well absorbed in male rats, showing a dose-dependent behavior.
Topics: Rats; Male; Female; Animals; Tandem Mass Spectrometry; Rats, Sprague-Dawley; Drugs, Chinese Herbal; Metabolome; Alkaloids; Lactones; Parabens
PubMed: 38145860
DOI: 10.1016/j.jep.2023.117582 -
Journal of Ethnopharmacology Mar 2024The stem of Musa paradisiaca (plantain) has found application in traditional medicine for the treatment of diabetes, inflammation, ulcers and wound injuries.
ETHNOPHARMACOLOGICAL RELEVANCE
The stem of Musa paradisiaca (plantain) has found application in traditional medicine for the treatment of diabetes, inflammation, ulcers and wound injuries.
AIM OF THE STUDY
This study investigated the phytochemical composition, toxicity profile, wound healing, anti-inflammatory and analgesic effects of aqueous Musa paradisiaca stem extract (AMPSE) in rats.
METHODS
Phytochemical analysis of methanol-MPSE was performed by gas chromatography-mass spectrometry (GC-MS). Acute toxicity testing was carried out through oral administration of a single dose of AMPSE up to 5 g/kg. Four separate groups of rats were used for the subacute toxicity testing (n = 6). Group 1 served as a normal control and did not receive AMPSE, groups 2-4 received AMPSE daily by gavage for 28 days. In the experiments with excision and incision wounds, the rats were treated with 10 w/w AMPS extract. The anti-inflammatory and analgesic effects of AMPSE were assessed using egg albumin-induced paw oedema and acetic acid-induced writhing methods, respectively. For the subacute, anti-inflammatory and analgesic studies, AMPSE was administered to the experimental rats at doses of 300, 600 and 900 mg/kg body weight.
RESULTS
Bioactive compounds identified include β-sitisterol, n-hexadecanoic acid, octadecanoic acid, diethyl sulfate, p-hydroxynorephedrine, phenylephrine, nor-pseudoephedrine, metaraminol, pseudoephedrine and vanillic acid. No signs of toxicity and no deaths were observed in all the groups. For the groups treated with AMPSE for 28 days, a significant reduction in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea, sodium, chloride, total cholesterol, triglycerides, and low-density lipoprotein cholesterol were observed while high density lipoprotein cholesterol, glutathione and superoxide dismutase increased compared to control (p < 0.05). In wound healing experiments, AMPSE showed greater percent wound contraction and wound resistance fracture compared to the povidone-iodine (PI) treated and control groups. Treatment with 900 mg/kg AMPSE resulted in significant (p < 0.05) anti-inflammatory and analgesic effects compared to the control.
CONCLUSION
This study shows that AMPSE is not toxic but contains biologically active compounds with hepatoprotective, anti-inflammatory, lipid-lowering and wound-healing effects. Treatment of rats with AMPSE has shown that AMPSE has anti-inflammatory, analgesic, hepatoprotective, lipid-lowering and wound-healing effects, supporting its therapeutic use in ethnomedicine.
Topics: Rats; Animals; Musa; Plant Extracts; Plantago; Musaceae; Pseudoephedrine; Analgesics; Anti-Inflammatory Agents; Wound Healing; Cholesterol; Phytochemicals; Lipids
PubMed: 38135229
DOI: 10.1016/j.jep.2023.117639 -
Zhongguo Zhong Yao Za Zhi = Zhongguo... Nov 2023This study comprehensively analyzed the active components of Sanhan Huashi Formula using qualitative and quantitative mass spectrometry techniques, laying the foundation...
This study comprehensively analyzed the active components of Sanhan Huashi Formula using qualitative and quantitative mass spectrometry techniques, laying the foundation for understanding its pharmacological substance basis. UHPLC-LTQ-Orbitrap-MS and GC-MS technologies were used to analyze and identify the volatile and non-volatile components in Sanhan Huashi Formula. UHPLC-QQQ-MS/MS technology was used to simultaneously determine the content of 27 major active components in the formula. The results showed that 308 major chemical components were identified in Sanhan Huashi Formula, among which 60 compounds were identified by comparing with reference standards, mainly including alkaloids, flavonoids, coumarins, triterpenoid saponins, amino acids, and nucleosides. GC-MS technology preliminarily identified 52 volatile compounds, with γ-eudesmol and β-eudesmol as the main components. The quantitative results demonstrated good linearity(r>0.99) for the 27 active components, indicating the stability, simplicity, and reliability of the established method. Among them, amygdalin, nodakenin, arecoline, ephedrine, and pseudoephedrine had relatively high content and were presumably the main pharmacologically active substances. In conclusion, this study systematically and comprehensively characterized the major chemical components and patterns in Sanhan Huashi Formula, providing a basis for understanding its pharmacological mechanisms and clinical applications.
Topics: Tandem Mass Spectrometry; Chromatography, High Pressure Liquid; Gas Chromatography-Mass Spectrometry; Reproducibility of Results; Drugs, Chinese Herbal
PubMed: 38114213
DOI: 10.19540/j.cnki.cjcmm.20230614.303 -
Biological & Pharmaceutical Bulletin 2023Ephedra herb, a dried terrestrial stem of Ephedra sinica, is used in traditional Japanese medicine (Kampo) and Chinese medicine to treat the common cold, headaches,...
Ephedra herb, a dried terrestrial stem of Ephedra sinica, is used in traditional Japanese medicine (Kampo) and Chinese medicine to treat the common cold, headaches, bronchial asthma, and nasal inflammation. E. sinica predominantly contains two ephedrine alkaloids-(-)-ephedrine and (+)-pseudoephedrine-which are crucial for its medicinal effects. This study aimed to reveal the influence of genetic and environmental factors on ephedrine alkaloids content using statistical genetic analyses. To evaluate the influence of genetic factors on ephedrine alkaloids content, 25 clonal lines were cultivated in Ibaraki and the broad-sense heritability of the traits was estimated. The heritabilities of (-)-ephedrine, (+)-pseudoephedrine, and "total alkaloids" (TA) content were 0.871, 0.969, and 0.865, respectively. The heritabilities of ephedrine alkaloids content were high. To evaluate the influence of environmental factors on ephedrine alkaloids content, four clonal lines which have different genotypes were cultivated in three locations (Ibaraki, Shizuoka, and Yamanashi prefectures). The effects of genotype (G), location (L), and genotype by environment (G × E) interactions on ephedrine alkaloids content were found to be significant (p < 0.05) by two-way ANOVA, and, in particular, the genotypic effects were found to be the largest. Our results indicate that the ephedrine alkaloids content in E. sinica is under relatively strong genetic control and remains stable under various environments. These findings suggest that E. sinica with a higher and stable ephedrine alkaloids content could be cultivated in different locations through selective breeding.
Topics: Ephedrine; Ephedra sinica; Pseudoephedrine; Alkaloids; Drugs, Chinese Herbal
PubMed: 38044092
DOI: 10.1248/bpb.b23-00374 -
Child Neurology Open 2023Cholinergic receptor nicotinic epsilon (CHRNE) subunit mutations cause postsynaptic type of congenital myasthenic syndrome either as a primary acetylcholine-receptor...
Cholinergic receptor nicotinic epsilon (CHRNE) subunit mutations cause postsynaptic type of congenital myasthenic syndrome either as a primary acetylcholine-receptor deficiency or abnormal channel kinetics in the receptor. We report a novel homozygous variant (c.322C > T, p.Pro108Ser) in the epsilon subunit causing primary acetylcholine-receptor deficiency in two siblings. Two siblings presented with fatigable weakness. Both siblings had whole exome sequencing showing a homozygous variant (c.322C > T, p.Pro108Ser) of unknown significance in the epsilon subunit. Electromyography/nerve conduction study with repetitive nerve stimulation on one sibling showed a defect in neuromuscular junction transmission. Pseudoephedrine and fluoxetine for suspected slow-channel congenital myasthenic syndrome yielded no improvement. A trial of pyridostigmine led to clinical improvement. Given the clinical presentation, consanguinity, homozygous genetic variant, and response to pyridostigmine, we rationalize the homozygous variant (c.322C > T, p.Pro108Ser) in cholinergic receptor nicotinic epsilon subunit causes the primary acetylcholine-receptor deficiency congenital myasthenic syndrome.
PubMed: 38034490
DOI: 10.1177/2329048X231216432 -
Expert Review of Clinical Pharmacology 2023The renewed interest in considering a range of stimulants, psychedelics and dissociatives as therapeutics emphasizes the need to draft an updated overview of these... (Review)
Review
INTRODUCTION
The renewed interest in considering a range of stimulants, psychedelics and dissociatives as therapeutics emphasizes the need to draft an updated overview of these drugs' clinical and pharmacological issues.
AREAS COVERED
The focus here was on: stimulants (e.g. amphetamines, methamphetamine, and pseudoephedrine; phenethylamines; synthetic cathinones; benzofurans; piperazines; aminoindanes; aminorex derivatives; phenmetrazine derivatives; phenidates); classical (e.g. ergolines; tryptamines; psychedelic phenethylamines), and atypical (e.g. PCP/ketamine-like dissociatives) psychedelics.Stimulant and psychedelics are associated with: a) increased central DA levels (psychedelic phenethylamines, synthetic cathinones and stimulants); b) 5-HT receptor subtypes' activation (psychedelic phenethylamines; recent tryptamine and lysergamide derivatives); and c) antagonist activity at NMDA receptors, (phencyclidine-like dissociatives).
EXPERT OPINION
Clinicians should be regularly informed about the range of NPS and their medical, psychobiological and psychopathological risks both in the acute and long term. Future research should focus on an integrative model in which pro-drug websites' analyses are combined with advanced research approaches, including computational chemistry studies so that in vitro and in vivo preclinical studies of index novel psychoactives can be organized. The future of psychedelic research should focus on identifying robust study designs to convincingly assess the potential therapeutic benefits of psychedelics, molecules likely to present with limited dependence liability levels.
Topics: Humans; Hallucinogens; Psychotropic Drugs; Central Nervous System Stimulants; Phenethylamines; Methamphetamine
PubMed: 37968919
DOI: 10.1080/17512433.2023.2279192 -
Drug and Alcohol Review Jan 2024Project Stop, a real-time monitoring program for pseudoephedrine-containing medicines, was initiated in 2005 by the Pharmacy Guild of Australia in collaboration with... (Review)
Review
ISSUES
Project Stop, a real-time monitoring program for pseudoephedrine-containing medicines, was initiated in 2005 by the Pharmacy Guild of Australia in collaboration with police in the state of Queensland. The program implemented an online database to record pseudoephedrine purchases (and attempted purchases) to prevent large-scale diversion to methamphetamine production.
APPROACH
This narrative review aims to understand the overall impact of Project Stop, what evidence exists for this kind of intervention in Australia, and what lessons can be learned from its introduction. Systematic database searches were conducted in Embase, PubMed, Web of Science and Google Scholar, with 20 relevant sources selected for inclusion.
KEY FINDINGS
Project Stop successfully prevented some pseudoephedrine from being diverted from pharmacies to methamphetamine production. The intervention has been most effective in jurisdictions that made the program mandatory. Project Stop was also associated with a temporary decline in clandestine laboratory seizures in Queensland, changes in methamphetamine production methods and reduced voluntary treatment admissions for methamphetamine use. Implementation was not associated with an appreciable effect on secondary indicators, such as methamphetamine production and harmful use.
IMPLICATIONS
Future applications of a Project Stop model must ensure ongoing impact evaluation, assessment of its effect on individual's drug-related behaviour and combine it with policies that address drug use as a health issue.
CONCLUSION
Project Stop has been narrowly successful in terms of reducing pseudoephedrine diversion and demonstrates the potential for third-party policing practices directed at the consumer level, in collaboration with healthcare practitioners, rather than only regulating precursor wholesalers.
Topics: Humans; Australia; Pharmacies; Pseudoephedrine; Methamphetamine; Substance-Related Disorders
PubMed: 37963493
DOI: 10.1111/dar.13777 -
Journal of Pharmaceutical and... Jan 2024Fingerprints left at a crime scene are used to connect the crime to a person who may have been present there. Fingerprints can also be used as alternative material in...
Fingerprints left at a crime scene are used to connect the crime to a person who may have been present there. Fingerprints can also be used as alternative material in forensic toxicology. The detection of drugs in fingerprint samples can be used to show that an individual touching an item has consumed specific drugs. The aim of this study was to check the usefulness of fingerprints in drug analyses and detection of some analytes in this material. Fingerprint samples were collected on glass slides from a volunteer who consumed separately tablets containing pseudoephedrine, codeine, dextromethorphan, and used lidocaine spray. Moreover, fingerprints of individuals receiving sertraline, hydroxyzine and trazodone as part of their long-term treatment were analysed. The detection of drugs was conducted using the liquid chromatography tandem mass spectrometry (LC-MS/MS) technique. After administration of single doses of drugs, they were detected up to 36 h (pseudoephedrine), 24 h (codeine), and less than 6 h (dextromethorphan and lidocaine) with maximum concentrations observed at 1-4 h. In fingerprints of a person who has finished treatment with hydroxyzine and sertraline it was possible to detect these drugs even 20 days after last drug administration. Cetirizine (hydroxyzine metabolite) and mCPP (trazodone metabolite) were determined in fingerprints of individuals under long-term treatment. This work has demonstrated that forensic toxicology can use fingerprints as alternative material. Drugs can be detected in fingerprints even after their single doses. Parent compounds predominate over metabolites in the fingerprints. The detection window depends on the type of drug and duration of the treatment.
Topics: Humans; Chromatography, Liquid; Trazodone; Tandem Mass Spectrometry; Dextromethorphan; Pseudoephedrine; Sertraline; Substance Abuse Detection; Pharmaceutical Preparations; Hydroxyzine; Codeine; Lidocaine
PubMed: 37926037
DOI: 10.1016/j.jpba.2023.115835