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The Medical Letter on Drugs and... Oct 2019
Review
Topics: Animals; Antimalarials; Diarrhea; Humans; Insect Bites and Stings; Malaria; Travel; Travel-Related Illness
PubMed: 31599872
DOI: No ID Found -
American Journal of Obstetrics and... Jul 2024Adenomyosis is one of the structural causes of abnormal uterine bleeding, which often presents as heavy menstrual bleeding. Mostly because of the poor understanding of...
BACKGROUND
Adenomyosis is one of the structural causes of abnormal uterine bleeding, which often presents as heavy menstrual bleeding. Mostly because of the poor understanding of its pathophysiology, medical management of adenomyosis-induced heavy menstrual bleeding is still a challenge. We have previously reported that glycolysis is crucial to endometrial repair following menstruation and that suppressed glycolysis can cause heavy menstrual bleeding.
OBJECTIVE
This study aimed to test the hypothesis that meclizine, a drug with an excellent safety profile, alleviates heavy menstrual bleeding in mice with induced adenomyosis using a simulated menstruation model.
STUDY DESIGN
Adenomyosis was induced in 36 female C57BL/6 mice using endometrial-myometrial interface disruption. Three months after induction, the mice were randomly divided into the following 3 groups: low-dose meclizine, high-dose meclizine, and controls. Treatment with meclizine or vehicle started shortly before the simulated menstruation procedure and ended before progesterone withdrawal. The amount of blood loss was quantified and uterine tissue was harvested for histologic evaluation of the grade of endometrial repair. We performed immunohistochemistry analysis of 4 proteins critically involved in glycolysis: Glut1 (glucose transporter 1), Hk2 (hexokinase 2), Pfkfb3 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3), and Pkm2 (pyruvate kinase M2). The extent of tissue fibrosis in both ectopic and eutopic endometria was evaluated using Masson trichrome staining.
RESULTS
In mice with induced adenomyosis, meclizine accelerated endometrial repair in a dose-dependent manner and reduced the amount of menstrual bleeding. Meclizine administration raised endometrial immunoexpression of Hk2 and Pfkfb3 but not of Glut1 or Pkm2. The extent of endometrial fibrosis was reduced following the meclizine administration. Remarkably, these favorable changes were accompanied by the suppression of lesional progression, as evidenced by the dose-dependent reduction in the extent of fibrosis (a surrogate for lesional progression).
CONCLUSION
These encouraging results, taken together, suggest that glycolysis may be a promising therapeutic target and that meclizine may hold therapeutic potential as a nonhormonal treatment for adenomyosis-induced heavy menstrual bleeding without exacerbating the disease.
Topics: Animals; Female; Endometrium; Adenomyosis; Mice; Meclizine; Mice, Inbred C57BL; Glycolysis; Disease Models, Animal; Menorrhagia; Pyruvate Kinase; Glucose Transporter Type 1
PubMed: 38367751
DOI: 10.1016/j.ajog.2024.02.016 -
In Silico Pharmacology 2022Meclizine is antihistamine and is used in combination with pyridoxine to treat motion sickness. The in-silico study of meclizine prediction studied showed that meclizine...
Meclizine is antihistamine and is used in combination with pyridoxine to treat motion sickness. The in-silico study of meclizine prediction studied showed that meclizine has anti-eczema activity with possible activity 95. This research aimed to explore the anti-eczema activity of meclizine. Therefore, five formulations of meclizine ointment have been prepared using different bases (white base, simple ointment base, hydrophilic petrolatum base, hydrophilic, and emulsifying ointment bases). The efficiency of meclizine ointment has been evaluated by testing the physical compatibility and stability, homogeneity and irritant effect, absorbance and spreadability, chemical identification, calibration curve, drug content (assay), and dissolution test. This is followed by evaluating the ointment's effectiveness on volunteers and molecular docking. Five creams trials have been prepared, and two formulas (F3, and F5) have been selected for further evaluation. The formulas three and five (F3, F5) have passed the physical and chemical tests and showed compatibility, homogenous, absorbed, non-irritant, and stable with calibration curve (R = 0.9999). Then, the F3 formula was selected by testing them on seven volunteers after evaluating the irritant test. Four of the volunteers showed excellent recovery, and three of the volunteers suffered from uncomforting feelings and the formation of new pills. Therefore, F5 has been tested by eight volunteers that contain high oleaginous activity; five showed an excellent recovery, while three of the volunteers showed no difference. According to that, F5 is more efficient for eczema patients than F3, and Meclizine showed promising activity as an anti-eczema that requires further evaluation in the future.
PubMed: 36062215
DOI: 10.1007/s40203-022-00129-x -
Stroke May 2024Mild chemical inhibition of mitochondrial respiration can confer resilience against a subsequent stroke or myocardial infarction, also known as preconditioning. However,...
BACKGROUND
Mild chemical inhibition of mitochondrial respiration can confer resilience against a subsequent stroke or myocardial infarction, also known as preconditioning. However, the lack of chemicals that can safely inhibit mitochondrial respiration has impeded the clinical translation of the preconditioning concept. We previously showed that meclizine, an over-the-counter antivertigo drug, can toggle metabolism from mitochondrial respiration toward glycolysis and protect against ischemia-reperfusion injury in the brain, heart, and kidney. Here, we examine the mechanism of action of meclizine and report the efficacy and improved safety of the ) enantiomer.
METHODS
We determined the anoxic depolarization latency, tissue and neurological outcomes, and glucose uptake using micro-positron emission tomography after transient middle cerebral artery occlusion in mice pretreated (-17 and -3 hours) with either vehicle or meclizine. To exclude a direct effect on tissue excitability, we also examined spreading depression susceptibility. Furthermore, we accomplished the chiral synthesis of )- and )-meclizine and compared their effects on oxygen consumption and histamine H1 receptor binding along with their brain concentrations.
RESULTS
Micro-positron emission tomography showed meclizine increases glucose uptake in the ischemic penumbra, providing the first in vivo evidence that the neuroprotective effect of meclizine indeed stems from its ability to toggle metabolism toward glycolysis. Consistent with reduced reliance on oxidative phosphorylation to sustain the metabolism, meclizine delayed anoxic depolarization onset after middle cerebral artery occlusion. Moreover, the ) enantiomer showed reduced H1 receptor binding, a dose-limiting side effect for the racemate, but retained its effect on mitochondrial respiration. )-meclizine was at least as efficacious as the racemate in delaying anoxic depolarization onset and decreasing infarct volumes after middle cerebral artery occlusion.
CONCLUSIONS
Our data identify )-meclizine as a promising new drug candidate with high translational potential as a chemical preconditioning agent for preemptive prophylaxis in patients with high imminent stroke or myocardial infarction risk.
PubMed: 38572656
DOI: 10.1161/STROKEAHA.123.044397 -
The Journal of Neuroscience : the... Aug 2022Chemotherapy-induced peripheral neuropathy (CIPN) affects ∼68% of patients undergoing chemotherapy, causing debilitating neuropathic pain and reducing quality of life....
Chemotherapy-induced peripheral neuropathy (CIPN) affects ∼68% of patients undergoing chemotherapy, causing debilitating neuropathic pain and reducing quality of life. Cisplatin is a commonly used platinum-based chemotherapeutic drug known to cause CIPN, possibly by causing oxidative stress damage to primary sensory neurons. Metabotropic glutamate receptors (mGluRs) are widely hypothesized to be involved in pain processing and pain mitigation. Meclizine is an H1 histamine receptor antagonist known to have neuroprotective effects, including an anti-oxidative effect. Here, we used a mouse model of cisplatin-induced CIPN using male and female mice to test agonists of mGluR8 and Group II mGluR as well as meclizine as interventions to reduce cisplatin-induced pain. We performed behavioral pain tests, and we imaged Ca activity of the large population of dorsal root ganglia (DRG) neurons For the latter, we used a genetically-encoded Ca indicator, Pirt-GCaMP3, which enabled us to monitor different drug interventions at the level of the intact DRG neuronal ensemble. We found that CIPN increased spontaneous Ca activity in DRG neurons, increased number of Ca transients, and increased hyper-responses to mechanical, thermal, and chemical stimuli. We found that mechanical and thermal pain caused by CIPN was significantly attenuated by the mGluR8 agonist, (S)-3,4-DCPG, the Group II mGluR agonist, LY379268, and the H1 histamine receptor antagonist, meclizine. DRG neuronal Ca activity elevated by CIPN was attenuated by LY379268 and meclizine, but not by (S)-3,4-DCPG. Furthermore, meclizine and LY379268 attenuated cisplatin-induced weight loss. These results suggest that Group II mGluR agonist, mGluR8 agonist, and meclizine are promising candidates as new treatment options for CIPN, and studies of their mechanisms are warranted. Chemotherapy-induced peripheral neuropathy (CIPN) is a painful condition that affects most chemotherapy patients and persists several months or longer after treatment ends. Research on CIPN mechanism is extensive but has produced only few clinically useful treatments. Using GCaMP Ca imaging in live animals over 1800 neurons/dorsal root ganglia (DRG) at once, we have characterized the effects of the chemotherapeutic drug, cisplatin and three treatments that decrease CIPN pain. Cisplatin increases sensory neuronal Ca activity and develops various sensitization. Metabotropic glutamate receptor (mGluR) agonist, LY379268 or the H1 histamine receptor antagonist, meclizine decreases cisplatin's effects on neuronal Ca activity and reduces pain hypersensitivity. Our results and experiments provide insights into cellular effects of cisplatin and drugs preventing CIPN pain.
PubMed: 35772967
DOI: 10.1523/JNEUROSCI.1064-21.2022 -
The Science of the Total Environment Oct 2023Aquatic ecosystems worldwide are strongly influenced by the productive activities of a region. These activities can generate pollution by compounds with little-known or...
Aquatic ecosystems worldwide are strongly influenced by the productive activities of a region. These activities can generate pollution by compounds with little-known or unknown characteristics and without regulation. Emerging contaminants are a group of compounds that have worldwide begun to be frequently detected in the environment, raising concern about their possible adverse effects on human and environmental health. Thus, it is important to generate a broader panorama of the dissemination of contaminants of emerging concern in the environment, implement actions to regulate their usage. This study aims to evaluate the occurrence and temporal distribution of oxandrolone and meclizine in surface water, sediments, tilapia muscle, and otter feces of the Ayuquila-Armería river, Mexico. Oxandrolone was detected in 55 % of the total analyzed samples, while meclizine was present in 12 %. In surface water, oxandrolone was present in 56 % of the samples, while meclizine in 8 %. In sediments, oxandrolone was detected in 45 % and meclizine was not detected. In tilapia muscle, oxandrolone was present in 47 % of samples and meclizine was not detected. In otters feces samples, oxandrolone and meclizine were present in 100 %. Regardless of the season (wet or dry), oxandrolone was detected in all four sample types, while meclizine was only detected in surface water and otter feces samples. Oxandrolone in the aquatic ecosystem of the Ayuquila-Armería basin showed that season variation generates a significant effect on their concentrations, especially in surface water and sediments. Meclizine did not show temporal variations either in seasons or between years. Particularly, oxandrolone concentrations presented an influence with respect to the sites that present continuous residual discharges to the river. In this sense, this study could be considered as a starting point for further routine monitoring of emerging contaminants to support regulation policies regarding their use and disposal.
Topics: Humans; Animals; Otters; Ecosystem; Environmental Monitoring; Water Pollutants, Chemical; Oxandrolone; Water; Meclizine; Mexico; Fishes; Rivers; Muscles; Feces; Geologic Sediments
PubMed: 37379920
DOI: 10.1016/j.scitotenv.2023.165130 -
PloS One 2020Achondroplasia (ACH) is the most common short-limbed skeletal dysplasia caused by activating mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. We...
Achondroplasia (ACH) is the most common short-limbed skeletal dysplasia caused by activating mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. We identified that meclizine hydrochloride inhibited FGFR3 signaling in various chondrocytic cells and promoted longitudinal bone growth in mouse model of ACH. Meclizine has safely been used for more than 50 years, but it lacks the safety data for repeated administration and pharmacokinetics (PK) when administered to children. We performed a phase Ia study to evaluate the PK and safety of meclizine administered orally to ACH children. Twelve ACH children aged from 5 to younger than 11 years were recruited, and the first 6 subjects received once a day of meclizine in the fasted condition, subsequent 6 subjects received twice a day of meclizine in the fed condition. Meclizine was well tolerated in ACH children with no serious adverse events. The mean Cmax, Tmax, AUC0-24h, t1/2 during 24 hours in the fasted condition were 130 ng/mL, 1.7 hours, 761 ng·h/mL, and 8.5 hours respectively. The simulation of repeated administration of meclizine for 14 days demonstrated that plasma concentration apparently reached steady state around 10 days after the first dose both at once a day and twice a day administration. The AUC0-10h of the fasting and fed condition were 504 ng·h/mL and 813 ng·h/mL, respectively, indicating exposure of meclizine increased with the diet. Although higher drug exposure was confirmed in ACH children compared to adults, a single administration of meclizine seemed to be well tolerated.
Topics: Achondroplasia; Administration, Oral; Animals; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Meclizine; Mice; Pharmacokinetics
PubMed: 32282831
DOI: 10.1371/journal.pone.0229639 -
BioRxiv : the Preprint Server For... Sep 2023Meclizine (Antivert, Bonine) is a first-generation H1 antihistamine used in the treatment of motion sickness and vertigo. Despite its wide medical use for over 70 years,...
Meclizine (Antivert, Bonine) is a first-generation H1 antihistamine used in the treatment of motion sickness and vertigo. Despite its wide medical use for over 70 years, its crystal structure and the details of protein-drug interactions remained unknown. In this study, we used microcrystal electron diffraction (MicroED) to determine the three-dimensional (3D) crystal structure of meclizine dihydrochloride directly from a seemingly amorphous powder. Two racemic enantiomers (R/S) were found in the unit cell, which packed as repetitive double layers in the crystal lattice. The packing was made of multiple strong N-H⋯Cl hydrogen bonding interactions and weak interactions like C-H⋯Cl and pi-stacking. Molecular docking revealed the binding mechanism of meclizine to the histamine H1 receptor. A comparison of the docking complexes between histamine H1 receptor and meclizine or levocetirizine (a second-generation antihistamine) showed the conserved binding sites. This research illustrates the combined use of MicroED and molecular docking in unraveling protein-drug interactions for precision drug design and optimization.
PubMed: 37786674
DOI: 10.1101/2023.09.05.556418 -
Journal of Special Operations Medicine... 2016The series objective is to review various clinical conditions/ presentations, including the latest evidence on management, and to dispel common myths. In the process,... (Review)
Review
The series objective is to review various clinical conditions/ presentations, including the latest evidence on management, and to dispel common myths. In the process, core knowledge and management principles are enhanced. A clinical case will be presented. Cases will be drawn from real life but phrased in a context that is applicable to the Special Operations Forces (SOF) or tactical emergency medical support (TEMS) environment. Details will be presented in such a way that the reader can follow along and identify how they would manage the case clinically depending on their experience and environment situation. Commentary will be provided by currently serving military medical technicians. The medics and author will draw on their SOF experience to communicate relevant clinical concepts pertinent to different operational environments including SOF and TEMS. Commentary and input from active special op.
Topics: Acupressure; Antiemetics; Cholinergic Antagonists; Dopamine Antagonists; Emergency Medical Technicians; Histamine Antagonists; Humans; Meclizine; Metoclopramide; Military Personnel; Motion Sickness; Ondansetron; Promethazine; Scopolamine
PubMed: 27450607
DOI: No ID Found -
Current Drug Research Reviews 2020A basic, powerful and isocratic chiral fluid chromatographic technique was created and approved for the enantiomeric partition of meclizine hydrochloride in...
OBJECTIVE
A basic, powerful and isocratic chiral fluid chromatographic technique was created and approved for the enantiomeric partition of meclizine hydrochloride in pharmaceutical dose structure.
METHODS
The chromatographic partition was accomplished on Phenomenex® Lux Cellulose 1 (250 mm x 4.6 mm i.d, 5 μm molecule size) section utilizing portable stage framework containing acetonitrile: 25mM ammonium bicarbonate (75:25%v /v). The versatile stage was siphoned on the segment at the stream pace of 1.0 mL/min, and UV recognition was done at 230 nm.
RESULT
The breaking points of recognition and measurement were observed to be 0.25 μg/mL and 1.00 μg/mL individually, for 20μL infusion volume. The alignment bend demonstrated phenomenal linearity over the focus scope of 1-5 μg/mL for (±) meclizine enantiomers with a relationship coefficient (r2 = 0.999). The recuperation investigation of meclizine from tablet plan was observed to be 97.33% and 98.81% separately. Meclizine standard arrangement and versatile stage were observed to be steady for in any event 32h. The meclizine enantiomers were very much settled with mean maintenance times of about (+) Meclizine at 13.14 min and (-) Meclizine at 14.33 min individually.
CONCLUSION
The created technique was broadly approved and demonstrated to be hearty, exact, exact and appropriate for the examination of meclizine enantiomers in tablet measurement structure and security investigations of meclizine.
Topics: Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Histamine H1 Antagonists; Meclizine; Stereoisomerism; Tablets; Time Factors
PubMed: 31823710
DOI: 10.2174/2589977511666191211123337