Repeated and uncontrolled seizures in epilepsy result in brain cell loss and neural inflammation. Current anticonvulsants primarily target ion channels and receptors implicated in seizure activity. Identification of neurotherapeutics that can inhibit epileptiform activity and reduce inflammation in the brain may offer significant benefits in the long-term management of epilepsy. Fenamates are unique because they are both non-steroidal anti-inflammatory drugs (NSAIDs) and highly subunit selective modulators of GABAA receptors. In the current study we have investigated the hypothesis that fenamates have antiseizure properties using mature human stem cell-derived neuro-glia cell cultures, maintained in long-term culture, and previously shown to be sensitive to first, second and third generation antiepileptics. Mefenamic acid, flufenamic acid, meclofenamic acid, niflumic acid, and tolfenamic acid (each tested at 10-100 μM) attenuated 4-aminopyridine (4-AP, 100 μM) evoked epileptiform activity in a dose-dependent fashion. These actions were as effective diazepam (3-30 μM) and up to 200 times more potent than phenobarbital (300-1,000 μM). The low (micromolar) concentrations of fenamates that inhibited 4-AP evoked epileptiform activity correspond to those reported to potentiate GABAA receptor function. In contrast, the fenamates had no effect on neural spike amplitudes, indicating that their antiseizure actions did not result from inhibition of sodium-channels. The antiseizure actions of fenamates were also not replicated by either of the two non-fenamate NSAIDs, ibuprofen (10-100 μM) or indomethacin (10-100 μM), indicating that inhibition of cyclooxygenases is not the mechanism through which fenamates have anticonvulsant properties. This study therefore shows for the first time, using functionally mature human stem cell-derived neuroglial circuits, that fenamate NSAIDs have powerful antiseizure actions independent of, and in addition to their well-established anti-inflammatory properties, suggesting these drugs may provide a novel insight and new approach to the treatment of epilepsy in the future.

The inappropriate use of analgesics and antibiotics is a widespread issue among dentists globally, leading to the risk of over-prescription that could negatively affect patient health and quality of life. This study aimed to assess the prescribing patterns of analgesics and antibiotics by dentists in Kirkuk City, Iraq, focusing on their attitudes, knowledge levels, and practices regarding these medications. A cross-sectional survey was conducted among 280 dentists in Kirkuk City. The dentists were contacted via their work email addresses, and they responded to a survey. Descriptive statistics, including frequency analysis, were employed to evaluate the appropriateness of analgesic and antibiotic prescriptions for different dental conditions. The first-choice analgesic for 44.6% of dentists was mefenamic acid, followed by paracetamol (31.1%). Regarding antibiotic use, 56.8% of dentists in Kirkuk City reported using antibiotics for empirical and direct therapy. Other dentists (43.2%) revealed that they did not have enough information regarding antibiotic group preference in empirical therapy. 106 of the participants (37.85%) recommended the use of broad-spectrum antibiotics in the treatment of bacterial infections. However, most (45%) were unfamiliar with the group preferences in empirical therapy. Dentists in Kirkuk City showed variations in knowledge and awareness regarding using analgesics and antibiotics. This requires further education and training on proper analgesics and antibiotic stewardship guidelines.

Aim: Amide-linked amylose-based prodrugs were developed for colon-targeted release of mefenamic acid. Materials & methods: Activation of prodrug was studied spectrophotometrically, enzyme-linked immunosorbent assay appraised cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) inhibition at different concentrations of the prodrug, the behavior of prodrug under physiological conditions was monitored by scanning electron microscopy. Results: Prodrug was poorly activated in the enzyme-free simulated gastric media and simulated intestinal media (SIM) but preincubation in pancreatin followed by treatment in aminopeptidase containing SIM led to a significant activation of prodrug. Conclusion: Amide-linked amylose-mefenamic acid conjugates showed a slow release in simulated gastric media and a controlled release in SIM with pancreatin playing an important role in drug release.

Perioperative hypersensitivity reactions vary from mild to potentially fatal anaphylaxis, resulting in significant morbidity and mortality. Most of the perioperative hypersensitivity and allergic reactions are attributed to antibiotics, antiseptic solutions, latex, and opioids. In the current thrust for opioid-free anesthesia, owing to its multiple advantages, paracetamol and nonsteroidal antiinflammatory agents play a significant role in multi-modal pain and inflammatory response management. Nearly nine out of ten individuals experience postoperative pain, one-third experience postoperative nausea and vomiting, and one-fourth experience fever, irrespective of surgery and type of anesthesia, often as an inflammatory response. While perioperative hypersensitivity reactions are common, a patient allergic to multiple commonly used drugs for the treatment of pain, fever, acid-peptic disorder, and nausea and vomiting is scarce. Such cases pose a great challenge in perioperative management. A 14-year-old male child with a traumatic foot drop planned for tibialis posterior tendon transfer developed an allergic reaction with mild fever following an injection of Ranitidine and Ondansetron in the preoperative area. Surgery was deferred and was investigated for allergy profile testing for commonly used drugs, which showed high IgE levels and moderate to severe hypersensitivity for diclofenac and paracetamol. The patient was operated on after one month under spinal anesthesia, avoiding ranitidine, ondansetron, diclofenac, and paracetamol. The following morning, he developed a high-grade fever (102.3° F), which did not resolve with conservative measures. Hypersensitivity and allergic reactions to NSAIDs are reported in the literature. While there are multiple drugs available as NSAIDs, cross-sensitivity or allergy to other drugs within the same group, and even chemically related groups, is also another possibility that needs to be considered while managing such patients. Mefenamic acid controlled the fever, and the child was discharged home after 48 hours of observation. However, the case posed a great perioperative management dilemma; the present report intends to highlight and discuss it.

UNASSIGNED: Needle pain due to routine vaccination is an important factor contributing to low vaccine adherence and immunization coverage. Prophylactic oral analgesics can address this important issue of needle pain related to vaccination. Paracetamol and mefenamic acid are commonly used nonsteroidal anti-inflammatory drugs for pain relief, but there is little published literature on whether the same can be used for needle pain related to vaccination.
UNASSIGNED: This study was planned to compare the efficacy of oral mefenamic acid and paracetamol over placebo as a prophylactic analgesic during vaccination and prophylactic antipyretic during the post-vaccination period.
UNASSIGNED: Three-arm, triple-blind, randomized controlled trial.
UNASSIGNED: This study was conducted at the outpatient department of a tertiary-level medical college in South India from January 2021 to June 2022. In this three-arm interventional trial, each arm had either a single dose of placebo or mefenamic acid (4 mg/kg/dose) or paracetamol (10 mg/kg/dose). These medicines were administered orally 30 min before vaccination to reduce needle pain.
UNASSIGNED: Outcome was measured with the change of FLACC (Face, Leg, Activity, Cry, Consolability) scoring at the time of vaccination, subsequently at 15 and 30 min of vaccination in all three groups. Appearance of fever, grade of fever, and need for antipyretics 24 h after vaccination were also noted.
UNASSIGNED: There was a significant difference in FLACC scores at the time of administration (p = 0.010) and at 15 min (p = 0.014) with mefenamic acid compared to placebo. Although the paracetamol group showed a difference when compared to the placebo, it was not significant at the time of administration (p = 0.401), at 15 min (p = 0.451), or 30 min (p = 0.892) post-vaccination. The appearance of fever, grade of fever, and use of antipyretic up to 24 h post-vaccination had no significant difference among any of the three groups.
UNASSIGNED: Mefenamic acid was more potent than placebo for pre-vaccination pain prophylaxis in children. There was no difference in the appearance of fever and its grade among the three groups. The promising results from this trial warrant further large-scale studies to recommend a single oral dose of mefenamic acid to tackle needle pain related to vaccination in children to improve vaccine adherence and coverage.
UNASSIGNED: CTRI (Clinical trials registry-India) (CTRI/2021/01/030239). [Date of Commencement: 13 Jan 2021, Date of last recruitment: 30 June 2022 (now closed for new participants)].

UNASSIGNED: Abnormal uterine bleeding (AUB) is a common problem in reproductive age group and perimenopausal age group being responsible for many outpatient visits. Traditional management of AUB consists of giving mefenamic acid, tranexamic acid, or their combination with progestogens or hormonal intrauterine deviced levonorgestrel intrauterine system (LNG-IUS) for severe or nonresponsive cases. The objective of the current study was to study the efficacy and safety of adding diosmin along with tranexamic acid and mefenamic acid in reducing menstrual blood loss in AUB patients.
UNASSIGNED: It was a prospective double-blind randomized controlled trial in which 900 mg of diosmin was given once daily along with 500 mg tranexamic acid and 250 mg mefenamic acid during menstruation (Group I-92 patients), or only tranexamic acid and mefenamic acid during menstruation (Group II-92 patients).
UNASSIGNED: Mean age, parity, body mass index, and socioeconomic status were similar in the two groups. It was 35.68 years versus 36.78 years, 2.2 versus 2.3, 23.68 kg/m2 versus 24.62 kg/m2 respectively. Mean days of bleeding before this treatment were 6.8 versus 6.6 (P = 0.33) and were 3.5 versus 5.2 (P = 0.02) after treatment. There was a significant reduction in both groups as compared to before treatment (P = 0.021 in Group I, 0.027 in Group II) but the reduction was greater in Group I (P = 0.02). The amount of blood loss was 385 ml versus 390 ml (P = 0.7) before treatment which was significantly reduced in both groups to 68 ml versus 112 ml (P = 0.02 in Group I, 0.03 in Group II) with more decrease in Group I than in Group II (P = 0.01). Mean hemoglobin at beginning of the study was 8.4 versus 8.5 g/dl in Group I and Group II (P = 0.02) and significantly increased in both groups posttreatment to 10.9 and 9.8 g/dl in Group I and Group II (P = 0.012 in Group I, 0.011 in Group II) with increase being more in Group I than Group II (P = 0.03). Pictorial blood assessment chart score was 398 versus 406 (P = 0.35) before treatment and decreased significantly to 86.5 and 110.5 (P = 0.001 in Group I, 0.001 in Group II) with more decrease being in Group I than II (P = 0.01). There was significant decrease in dysmenorrhea with both treatments with no difference in the two groups. Various adverse effects such as nausea, vomiting, abdominal pain, diarrhea, constipation, and headache were equal in the two groups.
UNASSIGNED: Both the group\'s diosmin with tranexamic acid and mefenamic acid (Group I) and tranexamic acid and mefenamic acid (Group II) were efficacious in reducing menstrual blood loss, number of menstrual days and dysmenorrhea with effect being more by addition of diosmin. Adverse effects were equal in both the two groups.

BACKGROUND: This work aimed to prepare niosomal formulations of an anticancer agent [mefenamic acid (MEF)] to enhance its cancer targeting. 131I was utilized as a radiolabeling isotope to study the radio-kinetics of MEF niosomes.
METHODS: niosomal formulations were prepared by the ether injection method and assessed for entrapment efficiency (EE%), zeta potential (ZP), polydispersity index (PDI) and particle size (PS). MEF was labeled with 131I by direct electrophilic substitution reaction through optimization of radiolabeling-related parameters. In the radio-kinetic study, the optimal 131I-MEF niosomal formula was administered intravenously (I.V.) to solid tumor-bearing mice and compared to I.V. 131I-MEF solution as a control.
RESULTS: the average PS and ZP values of the optimal formulation were 247.23 ± 2.32 nm and - 28.3 ± 1.21, respectively. The highest 131I-MEF labeling yield was 98.7 ± 0.8%. The biodistribution study revealed that the highest tumor uptake of 131I-MEF niosomal formula and 131I-MEF solution at 60 min post-injection were 2.73 and 1.94% ID/g, respectively.
CONCLUSIONS: MEF-loaded niosomes could be a hopeful candidate in cancer treatment due to their potent tumor uptake. Such high targeting was attributed to passive targeting of the nanosized niosomes and confirmed by radiokinetic evaluation.

UNASSIGNED: This study aimed to compare the efficacy of ibuprofen, Novafen, mefenamic acid (MA), and celecoxib for pain relief in patients with symptomatic irreversible pulpitis prior to emergency endodontic treatment.
UNASSIGNED: This clinical trial was conducted on 120 patients with moderate to severe pain due to symptomatic irreversible pulpitis seeking emergency endodontic treatment. The patients were randomly divided into 4 groups to receive Novafen, MA, Celecoxib, and ibuprofen. The pain score of patients was measured before and 1 hour after analgesic intake using a visual analog scale (VAS). The success of analgesic treatment was analyzed by the binary logistic regression model.
UNASSIGNED: A total of 117 patients including 76 females and 41 males with a mean age of 30.29 years completed the study and were statistically analyzed. Ibuprofen had the highest analgesic efficacy followed by Novafen, and caused a significantly greater reduction in pain score compared with MA and celecoxib [OR (Ibuprofen vs MA)=1.28, OR (Ibuprofen vs Celecoxib)=3.74, OR (Novafen vs MA)=2.94, OR (Novafen vs Celecoxib)=2.94, P<0.05]. Ibuprofen and Novafen had no significant difference in analgesic efficacy (P>0.05). Baseline pain score was a predictive factor for the success of analgesics (P<0.05). The success of analgesic treatment decreased by 0.68 times with each unit increase in pain score (P<0.05). Gender and age of patients had no significant effect on success of analgesics (P>0.05).
UNASSIGNED: Both ibuprofen and Novafen can serve as the analgesics of choice for pain relief in patients with symptomatic irreversible pulpitis with moderate to severe pain when emergency endodontic treatment cannot be immediately performed.

Vericiguat (Verquvo; US: Merck, other countries: Bayer) is a novel drug for the treatment of chronic heart failure. Preclinical studies have demonstrated that the primary route of metabolism for vericiguat is glucuronidation, mainly catalyzed by uridine diphosphate-glucuronosyltransferase (UGT)1A9 and to a lesser extent UGT1A1. Whereas a drug-drug interaction (DDI) study of the UGT1A9 inhibitor mefenamic acid showed a 20% exposure increase, the effect of UGT1A1 inhibitors has not been assessed clinically. This modeling study describes a physiologically-based pharmacokinetic (PBPK) approach to complement the clinical DDI liability assessment and support prescription labeling. A PBPK model of vericiguat was developed based on in vitro and clinical data, verified against data from the mefenamic acid DDI study, and applied to assess the UGT1A1 DDI liability by running an in silico DDI study with the UGT1A1 inhibitor atazanavir. A minor effect with an area under the plasma concentration-time curve (AUC) ratio of 1.12 and a peak plasma concentration ratio of 1.04 was predicted, which indicates that there is no clinically relevant DDI interaction anticipated. Additionally, the effect of potential genetic polymorphisms of UGT1A1 and UGT1A9 was evaluated, which showed that an average modest increase of up to 1.7-fold in AUC may be expected in the case of concomitantly reduced UGT1A1 and UGT1A9 activity for subpopulations expressing non-wild-type variants for both isoforms. This study is a first cornerstone to qualify the PK-Sim platform for use of UGT-mediated DDI predictions, including PBPK models of perpetrators, such as mefenamic acid and atazanavir, and sensitive UGT substrates, such as dapagliflozin and raltegravir.

Mefenamic acid (MFA) is a commonly prescribed non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory and analgesic properties. MFA is known to have potent antioxidant properties and a neuroprotective effect against oxidative stress. However, its impact on the liver is unclear. This study aimed to elucidate the antioxidative effects of MFA and their underlying mechanisms. We observed that MFA treatment upregulated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Treatment with various anthranilic acid derivative-class NSAIDs, including MFA, increased the expression of sequestosome 1 (SQSTM1) in HepG2 cells. MFA disrupted the interaction between Kelch-like ECH-associated protein 1 (Keap1) and Nrf2, activating the Nrf2 signaling pathway. SQTM1 knockdown experiments revealed that the effect of MFA on the Nrf2 pathway was masked in the absence of SQSTM1. To assess the cytoprotective effect of MFA, we employed tert-Butyl hydroperoxide (tBHP) as a ROS inducer. Notably, MFA exhibited a protective effect against tBHP-induced cytotoxicity in HepG2 cells. This cytoprotective effect was abolished when SQSTM1 was knocked down, suggesting the involvement of SQSTM1 in mediating the protective effect of MFA against tBHP-induced toxicity. In conclusion, this study demonstrated that MFA exhibits cytoprotective effects by upregulating SQSTM1 and activating the Nrf2 pathway. These findings improve our understanding of the pharmacological actions of MFA and highlight its potential as a therapeutic agent for oxidative stress-related conditions.