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European Journal of Pharmacology Mar 2024Fibromyalgia is a painful disorder of unknown aetiology that presents activation and recruitment of innate immune cells, including mast cells. Efforts have been made to...
Fibromyalgia is a painful disorder of unknown aetiology that presents activation and recruitment of innate immune cells, including mast cells. Efforts have been made to understand its pathogenesis to manage it better. Thus, we explored the involvement of peripheral mast cells in an experimental model of fibromyalgia induced by reserpine. Reserpine (1 mg/kg) was subcutaneously (s.c.) injected once daily in the back of male Swiss mice for three consecutive days. We analysed mechanical and cold allodynia, muscle fatigue and number of mast cell in plantar tissue. The fibromyalgia induction produced mast cell infiltration (i.e., mastocytosis) in the mice's plantar tissue. The depletion of mast cell mediators with the compound 48/80 (0.5-4 mg/kg, intraperitoneal (i.p.)) or the mast cell membrane stabilizer ketotifen fumarate (10 mg/kg, oral route (p.o.) widely (80-90 %) and extensively (from 1 up to 10 days) prevented reserpine-induced mechanical and cold allodynia and muscle fatigue. Compound 48/80 also prevented the reserpine-induced mastocytosis. Finally, we demonstrated that PAR-2, 5-HT, 5-HT, H, NK1 and MrgprB2 receptors, expressed in neuronal or mast cells, seem crucial to mediate fibromyalgia-related cardinal symptoms since antagonists or inhibitors of these receptors (gabexate (10 mg/kg, s.c.), ENMD-1068 (10 mg/kg, i.p.), ketanserin (1 mg/kg, i.p.), ondansetron (1 mg/kg, p.o.), promethazine (1 mg/kg, i.p.), and L733,060 (5 mg/kg, s.c.), respectively) transiently reversed the reserpine-induced allodynia and fatigue. The results indicate that mast cells mediate painful and fatigue behaviours in this fibromyalgia model, representing potential therapy targets to treat fibromyalgia syndrome.
Topics: Mice; Male; Animals; Fibromyalgia; Mast Cells; Hyperalgesia; Serotonin; Reserpine; Mastocytosis
PubMed: 38311276
DOI: 10.1016/j.ejphar.2024.176385 -
Caspian Journal of Internal Medicine 2023The use of transcutaneous electrical nerve stimulation (TENS) to relieve labor pain remains controversial and existing evidence is neither strong nor consistent. This...
BACKGROUND
The use of transcutaneous electrical nerve stimulation (TENS) to relieve labor pain remains controversial and existing evidence is neither strong nor consistent. This research was designed to compare TENS' effect with the injection of pethidine and promethazine in labor pain reduction.
METHODS
In this trial, for 45 pregnant women in the active phase of labor, TENS electrodes were placed (two on both arms, and two over the participants' low back) continuously for 120 minutes; and for another group 45 pregnant women, 100 milligrams of pethidine and 250 micrograms of promethazine were injected intramuscularly which could be repeated once at least one hour later. Labor pain and duration, need for labor induction/augmentation/other pain control methods/ instrumental delivery, delivery type, and maternal and newborn complications were measured in both groups.
RESULTS
The baseline mean visual analog scale (VAS) score, in the TENS group was 8.51±0.62 and in the pethidine and promethazine groups was 8.37±0.61 (P=0.31). While in a 120min post-intervention, it was 6.29±1.50 and 5.73±1.46 in the TENS group and the pethidine and promethazine group, respectively with no statistically significant difference (P=0.07). The labor duration in the TENS group was 6.61±1.71 hours and in the pethidine and promethazine group was 6.17±2.07 hours, with no statistically significant difference (P=0.33). In addition, no complication was recorded neither in the mothers nor newborns.
CONCLUSION
This study showed that applying TENS in the active labor phase can reduce at least two scores in patient labor pain with no significant complications.
PubMed: 38024177
DOI: 10.22088/cjim.14.4.62 -
Bioinformation 2023The use of antihistamine therapy in children for the management of upper respiratory tract infections remains a topic of debate. In this study, we focused on evaluating...
The use of antihistamine therapy in children for the management of upper respiratory tract infections remains a topic of debate. In this study, we focused on evaluating the effectiveness of promethazine (Phenergan), a first-generation H1 receptor antagonist and sedative, in addressing preoperative and intra-operative sequelae in cleft surgeries. A single-centered, parallel, randomized, double-blinded controlled clinical trial was conducted on 128 children aged 2 to 4 years undergoing cleft palate surgery under general anesthesia. The case group received Phenergan syrup orally twice a day for three days, while the control group received a placebo. Primary outcomes measured preoperative anxiety levels using a children's fear scale, while secondary outcomes assessed preoperative sleep quality and cough rate through objective scales. Intraoperative heart rate was monitored using an ECG connected to a monitor. The results demonstrated that the administration of promethazine resulted in a 34% reduction in anxiety levels, a 46% reduction in cold and cough, a 38% improvement in sleep score, and stable heart rates throughout the surgery compared to the control group. Based on these findings, promethazine is considered a safe premedication option for children undergoing cleft palate surgeries; given its benefits outweigh its adverse effects.
PubMed: 37885787
DOI: 10.6026/97320630019790 -
Journal of the Academy of... 2024Acute disturbance is a broad term referring to escalating behaviors secondary to a change in mental state, such as agitation, aggression, and violence. Available... (Review)
Review
Effectiveness and Safety of Intravenous Medications for the Management of Acute Disturbance (Agitation and Other Escalating Behaviors): A Systematic Review of Prospective Interventional Studies.
Acute disturbance is a broad term referring to escalating behaviors secondary to a change in mental state, such as agitation, aggression, and violence. Available management options include de-escalation techniques and rapid tranquilization, mostly via parenteral formulations of medication. While the intramuscular route has been extensively studied in a range of clinical settings, the same cannot be said for intravenous (IV); this is despite potential benefits, including rapid absorption and complete bioavailability. This systematic review analyzed existing evidence for effectiveness and safety of IV medication for management of acute disturbances. It followed a preregistered protocol (PROSPERO identification CRD42020216456) and is reported following the guidelines set by Preferred Reporting Items for Systematic Review and Meta-Analysis. APA PsycINFO, MEDLINE, and EMBASE databases were searched for eligible interventional studies up until May 30th, 2023. Data analysis was limited to narrative synthesis since primary outcome measures varied significantly. Results showed mixed but positive results for the effectiveness of IV dexmedetomidine, lorazepam, droperidol, and olanzapine. Evidence was more limited for IV haloperidol, ketamine, midazolam, chlorpromazine, and valproate. There was no eligible data on the use of IV clonazepam, clonidine, diazepam, diphenhydramine, propranolol, ziprasidone, fluphenazine, carbamazepine, or promethazine. Most studies reported favorable adverse event profiles, though they are unlikely to have been sufficiently powered to pick up rare serious events. In most cases, evidence was of low or mixed quality, accentuating the need for further standardized, large-scale, multi-arm randomized controlled trials with homogeneous outcome measures. Overall, this review suggests that IV medications may offer an effective alternative parenteral route of administration in acute disturbance, particularly in general hospital settings.
Topics: Humans; Administration, Intravenous; Psychomotor Agitation; Aggression; Antipsychotic Agents; Prospective Studies
PubMed: 38309683
DOI: 10.1016/j.jaclp.2024.01.004 -
International Journal of Pharmaceutics Aug 2023We present a physiologically based pharmacokinetic (PBPK) model simulating systemic drug concentrations following administration to the human rectum. Rectum physiology...
We present a physiologically based pharmacokinetic (PBPK) model simulating systemic drug concentrations following administration to the human rectum. Rectum physiology is parameterized based on literature data. The model utilizes in vitro release (IVRT) profiles from which drug mass transfer through the rectal fluid and tissue and into the systemic circulation are predicted. Due to a lack of data, rectal fluid and tissue absorption parameters are predicted either from colon absorption, with modifications relevant to rectal physiology, or optimized. The PBPK model is evaluated by simulating 29 clinical studies for 10 drugs. For 8 drugs (diazepam, diclofenac, indomethacin, naproxen, paracetamol, pentobarbital, phenobarbital and theophylline) the bias (average fold error, AFE) and precision (absolute average fold error, AAFE) of C, AUC and AUC simulations range from 0.87 to 2.22, indicating good agreement with observed values. For prochlorperazine and promethazine, the AFEs and AAFEs of C predictions are 1.30 and 2.52, respectively. TheAUC and AUC are overpredicted for both compounds(AFEs and AAFEs from 2.66 to 4.90). This results from a lack of reliable elimination data for prochlorperazine and the relevance of the IVRT profiles used in the promethazine model. The model paves the way for more mechanistic rectal drug absorption studies and virtual bioequivalence methods for rectal drug products.
Topics: Humans; Pharmaceutical Preparations; Rectal Absorption; Prochlorperazine; Promethazine; Therapeutic Equivalency; Models, Biological; Computer Simulation
PubMed: 37507097
DOI: 10.1016/j.ijpharm.2023.123273 -
RSC Advances Feb 2024In the current study, the association and phase separation of cationic tetradecyltrimethylammonium bromide (TTAB) and nonionic Triton X-100 (TX-100) surfactants with...
In the current study, the association and phase separation of cationic tetradecyltrimethylammonium bromide (TTAB) and nonionic Triton X-100 (TX-100) surfactants with promethazine hydrochloride (PMH) were investigated in aqueous ammonium-based solutions. The micellization nature of the TTAB and PMH drug mixture was examined by evaluating critical micelle concentration (CMC) and counterion binding extent () at different salt contents and temperatures (298.15-323.15 K). Micelle formation in the TTAB + PMH mixture was enhanced in the presence of ammonium salts, whereas the process was delayed with an increase in temperature in the respective salt solution. With an increase in salt content, the cloud point (CP) of the TX-100 + PMH mixture decreased, which revealed that the respective progression occurred through the salting out phenomenon. In micellization and clouding processes, the changes in free energies Δ and Δ were found to be negative and positive, respectively, demonstrating that the corresponding processes are spontaneous and non-spontaneous. Standard enthalpies (Δ/Δ) and standard entropies (Δ/Δ) for the association and clouding processes, respectively, were also calculated and discussed. The core forces amid TTAB/TX-100 and PMH in the manifestation of electrolytes are dipole-dipole and hydrophobic forces among the employed components according to the values for Δ/Δ and Δ/Δ, respectively.
PubMed: 38362074
DOI: 10.1039/d3ra07493e -
The Science of the Total Environment Feb 2024There is a growing concern about the presence of pharmaceuticals on the aquatic environment, while the marine environment has been much less investigated than in...
There is a growing concern about the presence of pharmaceuticals on the aquatic environment, while the marine environment has been much less investigated than in freshwater. Marine mammals are suitable sentinel species of the marine environment because they often feed at high trophic levels, have unique fat stores and long lifespan. Some small delphinids in particular serve as excellent sentinel species for contamination in the marine environment worldwide. To the best of our knowledge, no pharmaceuticals have been detected or reported in dolphins so far. In the present study, muscle, liver and blubber samples from three common dolphins (Delphinus delphis) and seven striped dolphins (Stenella coeruleoalba) stranded along the Basque Coast (northern Spain) were collected. A total of 95 pharmaceuticals based on detectability and predicted ability to bioaccumulate in fish were included in the liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. At least one pharmaceutical was found in 70 % of the individuals. Only three of the 95 monitored pharmaceuticals were detected in dolphin's tissues. Very low concentrations (<1 ng/g) of orphenadrine and pizotifen were found in liver and promethazine in blubber. Herein, the gap in the knowledge regarding the study organisms and marine environments with respect to pharmaceutical pollution, which demands further research to understand if pharmaceuticals are a threat for these apex predators, is highlighted and discussed.
Topics: Animals; Dolphins; Bays; Chromatography, Liquid; Tandem Mass Spectrometry; Stenella; Common Dolphins; Cetacea; Pharmaceutical Preparations
PubMed: 37979850
DOI: 10.1016/j.scitotenv.2023.168570 -
Biomedicine & Pharmacotherapy =... Jul 2024
Corrigendum to "Promethazine inhibits proliferation and promotes apoptosis in colorectal cancer cells by suppressing the PI3K/AKT pathway" [Biomed. Pharmacotherapy 143(2021)112174].
PubMed: 38876934
DOI: 10.1016/j.biopha.2024.116913 -
Future Microbiology 2024To evaluate the action of promethazine, fluoxetine and carbonyl cyanide 3-chlorophenylhydrazone as efflux pump inhibitors (EPIs) against multidrug-resistant . The...
To evaluate the action of promethazine, fluoxetine and carbonyl cyanide 3-chlorophenylhydrazone as efflux pump inhibitors (EPIs) against multidrug-resistant . The effect of the compounds was evaluated in planktonic cells and bacterial biofilms. Accumulation tests were performed with ethidium bromide to prove their action as EPIs. Then, they were associated with antimicrobials. Effect on planktonic cells and biofilms was found. Assays with ethidium bromide indicate their action as EPIs. Significant reductions in the metabolic activity of biofilms were observed after the association with the antimicrobials, especially for meropenem. It is possible to prove the action of these compounds as EPIs for and demonstrate the relevance of efflux pumps in antimicrobial resistance.
Topics: Pseudomonas aeruginosa; Drug Repositioning; Drug Resistance, Multiple, Bacterial; Anti-Bacterial Agents; Biofilms; Microbial Sensitivity Tests; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Promethazine; Membrane Transport Proteins; Humans; Bacterial Proteins; Pseudomonas Infections; Hydrazones
PubMed: 38629920
DOI: 10.2217/fmb-2023-0208 -
Analytica Chimica Acta Aug 2023Promethazine (PMZ) is an effective antihistamine that is used as a nerve tranquilizer to treat mental disorders. However, drug abuse causes harm to the human body and...
A highly selective and sensitive sensor for promethazine based on molecularly imprinted interface coated Au/Sn bimetal nanoclusters functionalized acupuncture needle microelectrode.
Promethazine (PMZ) is an effective antihistamine that is used as a nerve tranquilizer to treat mental disorders. However, drug abuse causes harm to the human body and also pollutes the environment to a certain extent. Therefore, it is crucial to develop a highly selective and sensitive biosensor for PMZ determination. An acupuncture needle (AN) was used as an electrode in 2015, and further research on the electrode's essence in electrochemistry is needed. In this work, a sensor based on a surface imprinted film coordinated Au/Sn biometal was first fabricated on AN via electrochemistry. The obtained cavities showed complementary and suitable sites for "N atom" electron transfer through the phenyl ring structure in promethazine, which is rigorous for the configuration near the interface. Under the optimal conditions, MIP/Au/Sn/ANE exhibits a good linear relationship in the range of 0.5 μM-500 μM, and the detection limit (LOD) is 0.14 μM (S/N = 3). The sensor exhibits good repeatability, stability, and selectivity and can be successfully used to analyze and detect PMZ in human serum and environmental water. The findings are scientifically significant for AN electrochemistry and the sensors have potential for in vivo medicamentosus monitoring in the future.
Topics: Humans; Microelectrodes; Promethazine; Molecular Imprinting; Electrodes; Needles; Acupuncture Therapy; Limit of Detection; Electrochemical Techniques; Biosensing Techniques
PubMed: 37290856
DOI: 10.1016/j.aca.2023.341395