Antihistamines Research Articles

Fexofenadine Hydrochloride Dispersible Tablets: A Taste Masking Strategy using Ion Exchange Resin

The pediatric population is more sensitive to allergies. Fexofenadine hydrochloride (FXD-HCL), a non-sedative antihistaminic drug, was chosen to create taste-masked patient-compliant pediatric dispersible tablets. Due to its bitter taste, fexofenadine hydrochloride is unsuitable for the formulation of dispersible tablets; therefore, Kyron T-134®, cation exchange resin was used to form a taste-masked complex with the drug to overcome its bitterness. The FXD HCL-resin complex was prepared using a kneading method and the complexation was confirmed by differential scanning calorimetry and FTIR studies. The FXD HCL-resin complex was evaluated for flow properties, degree of bitterness, assay and release study. Dispersible tablets were formulated by using a co-processed excipient, Granfiller-D211® containing croscarmellose sodium and crosspovidone, microcrystalline cellulose and mannitol. 22 factorial designs with two replicates optimized the dispersible tablets. The tablets, prepared using the direct compression technique on a single-stroke tablet compression machine, were elegant in appearance. Various pre and post-compression tests were conducted on all formulations. The tablets of hardness 3.5 kg/cm2 showed friability, disintegration time, assay within the compendial limit and showed immediate release of a drug (NLT 60% in 10 min and NLT 80% in 30 minutes) in 0.001 N HCl (pH 3). The DSC thermogram indicated partial amorphization of the FXD HCL. Dispersible tablets of fexofenadine hydrochloride and Granfiller-D®211 at 1:4 proportion was stable for one month at ambient and accelerated storage conditions.

Oral Dissolving Films: A Review

Oral dissolving films (ODFs) are thin, flexible, and fast-dissolving sheets that can deliver active substances to the oral cavity. They offer several advantages over conventional oral dosage forms, such as ease of swallowing, precise dosing, improved patient compliance, and rapid onset of action. ODFs can be used for various therapeutic applications, such as anti-ulcer, anti-asthmatic, antihistamine, and analgesic drugs. This review article presents a comprehensive analysis of recent advancements in ODF formulation, manufacturing techniques, and their diverse applications in pharmaceutical, nutraceutical, and biomedical fields. The formulation of ODFs involves the selection of suitable polymers, plasticizers, surfactants, flavours, and sweeteners. The polymers are the main component that determines the mechanical properties, disintegration time, and drug release profile of the films. The plasticizers are added to improve the flexibility and elasticity of the films. The surfactants are used to enhance the solubility and permeability of the drugs. The flavours and sweeteners are used to mask the unpleasant taste of the drugs and improve the palatability of the films. The production methods of ODFs include solvent casting, hot melt extrusion, and roll casting. These methods differ in terms of the equipment, process parameters, and film quality. Each technique's advantages, limitations, and potential for scalability are outlined, providing insight into the critical factors influencing ODF development. In summary, this review article provides a comprehensive overview of the recent progress in ODF technology, encompassing formulation optimization, manufacturing advancements, and innovative applications. As the field of oral dissolving films continues to evolve, this article offers valuable insights for researchers, clinicians, and pharmaceutical industry stakeholders seeking to harness the full potential of this versatile drug delivery platform. Keywords: Oral dissolving films, Plasticizer, Solvent casting method, Hot melt extrusion, Roll casting

Meclizine moderates lipopolysaccharide-induced neuroinflammation in mice through the regulation of AKT/ NF-κβ/ERK/JNK signaling pathway

Neuroinflammation is identified as significant inflammatory reactions occurring in the central nervous system. Lipopolysaccharide (LPS) stimulates innate immune reactions and is used as an in vivo animal model for the investigation of inflammation. Meclizine (MCLZ) is a histamine antagonist with potential neuroprotective qualities. Forty adult male Swiss albino mice were divided into four groups (n = 10). Group 1 served as a control negative group. Groups 2–4 were injected with LPS (5 mg/kg; i.p). Group 2 served as LPS-control. Groups 3 & 4 were given MCLZ (12.5 & 25 mg/kg; p.o) respectively for 14 days. LPS administration resulted in significant neuroinflammation in mice as was revealed by significant inflammatory histopathological changes and positive immunohistochemical staining of glial fibrillary acidic proteins (GFAP) accompanied by significant elevations of brain tissue contents of interleukin-1-beta (IL-1β), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-beta (NF-κβ), protein kinase B (AKT), extracellular signal-regulated kinase (ERK) and C-Jun N-Terminal Kinases (JNK). MCLZ treatment significantly down-regulated all the aforementioned parameters in mice brains. Moreover, MCLZ treatment ameliorated the inflammatory histopathological changes and GFAP immunostaining in brain tissues. The current study identifies for the first time the protective anti-neuroinflammatory effects of MCLZ against LPS-induced neuroinflammation in mice. MCLZ protected against neuroinflammation via the amelioration of inflammatory histopathological changes as well as neuronal GFAP immunostaining and down-regulated the AKT/NF-κβ/ERK/JNK signaling pathway. MCLZ is anticipated as a potential protective candidate for the addition to the treatment protocol of neuroinflammation.

Targeting MDM2-p53 Axis through Drug Repurposing for Cancer Therapy: A Multidisciplinary Approach.

Cancer remains a major cause of morbidity and mortality worldwide, and while current therapies, such as chemotherapy, immunotherapy, and cell therapy, have been effective in many patients, the development of novel therapeutic options remains an urgent priority. Mouse double minute 2 (MDM2) is a key regulator of the tumor suppressor protein p53, which plays a critical role in regulating cellular growth, apoptosis, and DNA repair. Consequently, MDM2 has been the subject of extensive research aimed at developing novel cancer therapies. In this study, we employed a machine learning-based approach to establish a quantitative structure-activity relationship model capable of predicting the potential in vitro efficacy of small molecules as MDM2 inhibitors. Our model was used to screen 5883 FDA-approved drugs, resulting in the identification of promising hits that were subsequently evaluated using molecular docking and molecular dynamics simulations. Two antihistamine drugs, cetirizine (CZ) and rupatadine (RP), exhibited particularly favorable results in the initial in silico analyses. To further assess their potential use as the activators of the p53 pathway, we investigated the antiproliferative capability of the abovementioned drugs on human glioblastoma and neuroblastoma cell lines. Both the compounds exhibited significant antiproliferative effects on the abovementioned cell lines in a dose-dependent manner. The half-maximal inhibitory concentration (IC50) of CZ was found to be 697.87 and 941.37 μM on U87 and SH-SY5Y cell lines, respectively, while the IC50 of RP was found to be 524.28 and 617.07 μM on the same cell lines, respectively. Further investigation by quantitative reverse transcriptase polymerase chain reaction analysis revealed that the CZ-treated cell lines upregulate the expression of the p53-regulated genes involved in cell cycle arrest, apoptosis, and DNA damage response compared to their respective vehicle controls. These findings suggest that CZ activates the p53 pathway by inhibiting MDM2. Our results provide compelling preclinical evidence supporting the potential use of CZ as a modulator of the MDM2-p53 axis and its plausible repurposing for cancer treatment.

The evaluation of photochemical behavior of antihistaminic drug triprolidine in an aqueous media.

Photodegradation is widely known as a changer of both the quality and the quantity of several chemical compounds. In this study, we sought to examine the photochemical behavior of triprolidine (TRP), which is a member of the first-generation antihistamine and utilized for a relief of an allergic conditions, in an aqueous media. There are no reports focused on its potential photoproducts and photodegradation pathways in detail to the best of our knowledge. TRP photodegradation induced by ultraviolet light (UV) irradiation was monitored utilizing high-performance liquid chromatography (HPLC), and structural elucidation of the TRP photoproduct was performed by electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) and nuclear magnetic resonance (NMR). Finally, the mechanism of TRP photodegradation was speculated based on the identified photoproduct. TRP was photodegraded dependent on the irradiation time of UV in proportion to the generation of one TRP photoproduct (TRP-P). Structural determination by LC-ESI-MS/MS and NMR clarified that TRP-P was the geometrical isomer of TRP, which was formed by the cis-trans conversion of double bond. UV irradiation experiment for TRP-P revealed the conversion from it to TRP. It is clarified that cis-trans conversion between TRP and TRP-P is photo-equilibrium reaction and TRP-P is predominant under the condition as this experiment. Toxicological potencies of TRP and TRP-P might not be observed by ProTox-II in silico toxicity evaluation. This is the first study evaluating the photochemical behavior of TRP.

Sedating antihistamine treatment with promethazine in patients with severe COPD with and without asthma: death and severe exacerbations in a nationwide register study

ABSTRACT Background Sedating antihistamines such as promethazine are used as anxiolytics and hypnotic agents for patients with chronic obstructive pulmonary disease (COPD) with and without asthma despite limited knowledge of its effects and side effects. We evaluated if treatment with promethazine had a lower risk of harmful outcome. Methods Nationwide retrospective cohort study of Danish specialist diagnosed outpatients with COPD treated with promethazine or an active comparator (melatonin). Patients with collection of promethazine or melatonin were propensity score matched 1:1. The primary outcome was a composite of severe COPD exacerbations and death from all causes analyzed by Cox proportional hazards regression. We performed an interaction analysis for comorbid asthma. Results In our registry of 56,523 patients with COPD, 5,661 collected promethazine (n = 3,723) or melatonin (n = 1,938). A cohort of 3,290 promethazine- or melatonin-treated patients matched 1:1 was available for the primary analysis. Within 1-year patients treated with promethazine were at higher risk of the primary outcome than matched controls with a Hazard Ratio (HR) of 1.42 (CI 1.27–1.58, p < 0.0001). Similarly, the risk of death was higher for promethazine-treated patients (HR 1.53, CI 1.32–1.77, p < 0.0001). An interaction analysis for comorbid asthma showed no interaction between comorbid asthma and the likelihood of a primary outcome when collecting promethazine (p = 0.19). Adjusted Cox analysis on the entire population indicated a further increased risk with more promethazine (HR for primary outcome among patients collecting ≥ 400 promethazine tablets/year=2.15, CI 1.94–2.38, p<0.0001). Conclusions Promethazine-treated patients with COPD had a concerning excess risk of a composite outcome of severe exacerbations and death from all causes compared to melatonin.

Prevalence, Risk Factors, and Management of Postoperative Nausea and Vomiting After Laparoscopic Sleeve Gastrectomy (a Retrospective Multicentric Study).

Postoperative nausea and vomiting (PONV) is a frequent unappealing laparoscopic sleeve gastrectomy (LSG) sequel. The study's purpose was to determine the prevalence, risk factors of PONV, and management of PONV after LSG. This multicenter retrospective study included patients with morbid obesity who had LSG between January 2022 and April 2023. The age range for LSG was 16 to 65years, and the eligibility requirements included morbid obesity according to international guidelines. PONV was experienced by 74.6% of patients who underwent LSG at 6h postoperative. Multivariate analysis revealed that female gender, smokers, preoperative GERD, gastropexy, and severity of pain were found to be independent risk variables of the development of PONV, while antral preservation, opioid-free analgesia, and intraoperative combined analgesia were found to be independent protective variables against the development of PONV. Combined intravenous ondansetron and metoclopramide improved 92.6% of patients who developed PONV. Dexamethasone and antihistamines drugs are given for 42 cases with persistent PONV after using intravenous ondansetron and metoclopramide. Pain management postoperatively by opioid-free analgesia managed PONV. Helicobacter pylori status has no role in the development of PONV after LSG. Female gender, smoking, presence of preoperative GERD, gastropexy, and severity of pain were found to be independent risk variables of the development of PONV, while antral preservation, opioid-free analgesia, and intraoperative combined analgesia were observed to be independent protective factors against the occurrence of PONV. Combined intravenous ondansetron and metoclopramide improved PONV. Dexamethasone and antihistamines drugs are given for persistent PONV.

Validation and Greenness assessment of UPLC Method for bioanalysis of Bilastine in mice PK study

Bilastine, is a second-generation antihistamine drug which is used in the treatment of allergic rhinoconjunctivitis and urticaria. It exerts its effect as a selective histamine H1 receptor antagonist. In this study, an ultra-high-performance liquid chromatography (UPLC) method was developed to measure the concentrations of Bilastine in mouse blood, and the method was applied in measuring the pharmacokinetics of the analyte after oral and intravenous administration. The analyte was extracted by solid phase extraction method. A UPLC BEH C18 column (2.1 mm × 100 mm, 1.8 ?m particle size) was used for chromatographic separation by gradient elution using acetonitrile-water (0.1% formic acid) as the mobile phase at a flow rate of 0.4 mL/min. Bilastine was administered to the mice orally at 2 mg/kg and intravenously at 0.05 mg/kg. Blood was collected at various time intervals, and the blood samples were processed after collection and analyzed by UPLC. The intra-day and inter-day accuracy of Bilastine were 91%-103% and 85%-107%, respectively, and the precision (RSD, %) was less than 15% for both intra-day and inter-day measurements. The matrix effect ranged from 95% to 108%, and the recovery was higher than 70%. The half-life of bilastine in plasma was found to be 7.02 ± 5.21h. Bilastine has a good linear relationship in the range of 10-500 ng/mL, and the lower limit of quantification was 10 ng/mL. The precision, accuracy, extraction recovery, matrix effect, and stability meet the requirements of the guiding principles. A robust and reliable UPLC method was fully optimized and developed to detect the blood concentration of bilastine in mice and the samples were analyzed by Empower software.

The analysis of the range of antihistamines at the pharmaceutical market of Ukraine

Aim. To analyze the range of antihistamines (AH) at the pharmaceutical market of Ukraine.&#x0D; Materials and methods. The analysis of the range of drugs was carried out in accordance with the State Register of Medicines of Ukraine as of February 2023, the weekly “Apteka” to determine the data of actual sales of AH. Statistical, frequency and graphic methods were used in the analysis. The information was processed using Microsoft Office Excel. &#x0D; Results. As a result of the frequency analysis, it was found that the pharmaceutical market of Ukraine as of February 2023 of AН for systematic use was represented by 170 trade names (TN) and 135 international non-proprietary names (INN). The leaders by INN were Desloratadine (34 TN) and Levocetirizine (26 TN). According to the State Register of Medicines of Ukraine as of February 2023, there were different drug forms, namely: tablets, solutions, drops, syrups, dragees and granules for the preparation of oral suspension. The largest share was AH in the form of tablets (70.59 %), solutions, drops, and syrups accounted for almost the same percentage (10 %, 9,41 %, 8,82 %), and 2 % of AH were registered in the form of dragees. The ratio of AH producing countries at the pharmaceutical market of Ukraine by TN was also determined. It was found that among the dosage forms presented, 62 % were of foreign production. AH of domestic production were 38 %; moreover, the largest market share (19 %) was produced by LLC Pharmaceutical Company “Zdorovye”. According to the results of the official data of weekly “Apteka” on the actual consumption of AH, it was found that AH of the second generation were the most popular both by INN and TN. It is due to their pharmacokinetic properties and the optimal price/effectiveness ratio.&#x0D; Conclusions. Based on the above, we can conclude that the pharmaceutical market of Ukraine is represented by a wide range of AH in various forms of production and various manufacturers. This leads to a wide choice of drugs of this group among the population, pharmaceutical and medical professionals.

Structural, Quantum Chemical, Spectroscopic (UV, FT-IR, FT-Raman and NMR) and Molecular Docking Studies of Diphenylpyraline Hydrochloride as Antihistaminic Drug

Diphenylpyraline hydrochloride, chemically known as 4-benzhydryloxy-1-methypiperidine hydrochloride is a first-generation antihistaminic drug that produces therapeutic antiallergic effects by binding to histamine H1 -receptors. The molecular structural and electronic properties of title compound have been computed at DFT/TD-DFT method with B3LYP/6-311++G(d,p) level. The theoretical spectral data has been compared with experimental ones, showing good agreement. The atomic charges, molecular electrostaitc potential (MEP), the natural bond orbitals (NBOs), the natural hybrid orbital (NHOs), the non-lilear optical (NLO) properties, the vibrational (IR and Raman) frequencies, UV-vis absorption wavelenghts and nuclear magnetic resonance (NMR) chemical shifts of diphenylpyraline hydrochloride have been investigated. The potential energy distribution (PED) of title compound was performed using the VEDA program and these values were compared with the experimental FT-IR and FT-Raman vibrational frequencies. Moreover, molecular docking studies have been performed between the 3RZE and 7DFL target proteins and the title compound. Docking results revealed that the title compound can be designed as potential antihistaminic agent.

Recognition and practice patterns of sexual medicine experts towards postorgasmic illness syndrome.

Post-orgasmic illness syndrome (POIS) is a rare, but debilitating cluster of symptoms, occurring after ejaculation with unknown mechanism and uncertain treatment. To the best of our knowledge, this study, which is thought to be the first in the literature, is aimed to investigate the practice patterns of sexual medicine experts towards POIS. Worldwide sexual medicine experts were invited to participate anonymously in an online, open survey using SurveyMonkey between November 14, 2022, and January 15, 2023. In total 211 sexual medicine experts filled the survey. The majority of the participants were urologists (83.9%). Most participants stated that the available information about POIS was inadequate for both patients and physicians. 47.9% of the participants stated psychological disorder, 46.4% stated bio-psycho-social reasons for the responsibility for the pathophysiology of POIS. 56.4% of the participants stated that they would refer the patient for psychotherapy/sexual therapy to a sexologist, 41.7% would prefer antihistamine drugs to manage symptoms. Only 18% of participants reported symptom improvement in more than 30% of the patients. This survey study among sexual medicine experts from different parts of the world has developed representative estimates of knowledge, attitudes and practice patterns regarding POIS worldwide.

Electrochemical Analysis of the Antihistamine Drug Cetirizine at a Poly(Glutamine) Modified Carbon Nanotube Paste Electrode

AbstractAn inexpensive and efficient sensor was developed for the electrochemical analysis of the antihistamine drug cetirizine (CTZ). The active sites on the bare carbon nanotube paste electrode surface were improved by the electropolymerization of poly(Glutamine). This modified electrode enhances the electrochemical response of the examining molecule. The study was conducted using a cyclic voltammetry technique in phosphate buffer saline of physiological pH 7.0 at a scan rate of 0.1 V/s. The developed electrode possesses increased conductance and declined overpotential for the determination of CTZ. At the optimized conditions, the detection limit was evaluated by obtaining the current response of CTZ at the varied concentration, and it was obtained as 0.12 μM. The poly glutamine modified carbon nanotube paste electrode was successfully applied to determine CTZ in tablet and human urine samples with acceptable recovery.

Current state and prospects of artificial intelligence in allergy.

The field of medicine is witnessing an exponential growth of interest in artificial intelligence (AI), which enables new research questions and the analysis of larger and new types of data. Nevertheless, applications that go beyond proof of concepts and deliver clinical value remain rare, especially in the field of allergy. This narrative review provides a fundamental understanding of the core concepts of AI and critically discusses its limitations and open challenges, such as data availability and bias, along with potential directions to surmount them. We provide a conceptual framework to structure AI applications within this field and discuss forefront case examples. Most of these applications of AI and machine learning in allergy concern supervised learning and unsupervised clustering, with a strong emphasis on diagnosis and subtyping. A perspective is shared on guidelines for good AI practice to guide readers in applying it effectively and safely, along with prospects of field advancement and initiatives to increase clinical impact. We anticipate that AI can further deepen our knowledge of disease mechanisms and contribute to precision medicine in allergy.

Formulation optimization, in vitro and in vivo evaluation of niosomal nanocarriers for enhanced topical delivery of cetirizine

Cetirizine hydrochloride (CTZ), a second-generation anti-histaminic drug, has been recently explored for its effectiveness in the treatment of alopecia. Niosomes are surfactant-based nanovesicular systems that have promising applications in both topical and transdermal drug delivery. The aim of this study was to design topical CTZ niosomes for management of alopecia. Thin film hydration technique was implemented for the fabrication of CTZ niosomes. The niosomes were examined for vesicle size, surface charge, and entrapment efficiency. The optimized niosomal formulation was incorporated into a hydrogel base (HPMC) and explored for physical characteristics, ex vivo permeation, and in vivo dermato-kinetic study. The optimized CTZ-loaded niosomal formulation showed an average size of 403.4 ± 15.6 nm, zeta potential of − 12.9 ± 1.7 mV, and entrapment efficiency percentage of 52.8 ± 1.9%. Compared to plain drug solution, entrapment of CTZ within niosomes significantly prolonged in vitro drug release up to 12 h. Most importantly, ex-vivo skin deposition studies and in vivo dermato-kinetic studies verified superior skin deposition/retention of CTZ from CTZ-loaded niosomal gels, compared to plain CTZ gel. CTZ-loaded niosomal gel permitted higher drug deposition percentage (19.2 ± 1.9%) and skin retention (AUC0-10h 1124.5 ± 87.9 μg/mL.h) of CTZ, compared to 7.52 ± 0.7% and 646.2 ± 44.6 μg/mL.h for plain CTZ gel, respectively. Collectively, niosomes might represent a promising carrier for the cutaneous delivery of cetirizine for the topical management of alopecia.

CdO Decorated with Polypyrrole Nanotube Heterostructure: Potent Electrocatalyst for the Detection of Antihistamine Drug Promethazine Hydrochloride in Environmental Samples.

In the realm of electrochemical sensor application, the development and fabrication of semiconducting metal oxides with the integration of conducting polymers for the trace-level detection of pharmaceutical medicines garnered considerable interest. Herein, we reported facile cadmium oxide decorated with polypyrrole nanotubes fabricated on a glassy carbon electrode (CdO@PPy/GCE) for efficient determination of antihistamine drug promethazine hydrochloride (PMH). The as-synthesized CdO@PPy composite was characterized by various analytical tools like X-ray powder diffraction, Fourier transform infrared spectroscopy, Raman spectroscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. Furthermore, the electrocatalytic activity of the modified electrode for PMH detection was examined by voltammetry and amperometric methods, and the modified electrode exhibited lower charge transfer resistance compared to the bare GCE. Under the optimized condition, the fabricated electrode shows a wide linear range (50-550 μM), better sensitivity (0.13 μAμM-1 cm-2), low detection limit (10.83 nM) (S/N = 3), and excellent selectivity and reproducibility toward PMH detection. Moreover, the modified GCE depicted eminent practical ability for PMH detection in lake water and pharmaceutical tablets.

Computational modeling (in silico) methods combined with ecotoxicological experiments (in vivo) to predict the environmental risks of an antihistamine drug (loratadine)

This study employed computational modeling (in silico) methods, combined with ecotoxicological experiments (in vivo) to predict the persistence/biodegradability, bioaccumulation, mobility, and ecological risks of an antihistamine drug (Loratadine: LOR) in the aquatic compartment. To achieve these goals, four endpoints of the LOR were obtained from different open-source computational tools, namely: (i) “STP total removal”; (ii) Predicted ready biodegradability; (iii) Octanol-water partition coefficient (KOW); and (iv) Soil organic adsorption coefficient (KOC). Moreover, acute and chronic, ecotoxicological assays using non-target freshwater organisms of different trophic levels (namely, algae Pseudokirchneriella subcapitata; microcrustaceans Daphnia similis and Ceriodaphnia dubia; and fish Danio rerio), were used to predict the ecological risks of LOR. The main results showed that LOR: (i) is considered persistent (after a weight-of-evidence assessment) and highly resistant to biodegradation; (ii) is hydrophobic (LOG KOW = 5.20), immobile (LOG KOC = 5.63), and thus, it can potentially bioaccumulate and/or can cause numerous deleterious effects in aquatic species; and (iii) after ecotoxicological evaluation is considered “toxic” and/or “highly toxic” to the three trophic levels tested. Moreover, both the ecotoxicological assays and risk assessment (RQ), showed that LOR is more harmful for the crustaceans (RQcrustaceans = moderate to high risks) than for algae and fish. Ultimately, this study reinforces the ecological concern due to the indiscriminate disposal of this antihistamine drug in worldwide aquatic ecosystems.

Negative modulation of the GABAAρ1 receptor function by histamine

Besides its function as a local mediator of the immune response, histamine can play a role as a neurotransmitter and neuromodulator. Histamine actions are classically mediated through four different G protein-coupled receptor subtypes but non-classical actions were also described, including effects on many ligand-gated ion channels. Previous evidence indicated that histamine acts as a positive modulator on diverse GABAA receptor subtypes, such as GABAAα1β2γ2, GABAAα2β3γ2, GABAAα3β3γ2, GABAAα4β3γ2 and GABAAα5β3γ2. Meanwhile, its effects on GABAAρ1 receptors, known to stand for tonic currents in retinal neurons, had not been examined before. The effects of histamine on the function of human homomeric GABAAρ1 receptors were studied here, using heterologous expression in Xenopus laevis oocytes followed by the electrophysiological recording of GABA-evoked Cl− currents. Histamine inhibited GABAAρ1 receptor-mediated responses. Effects were reversible, independent of the membrane potential, and strongly dependent on both histamine and GABA concentration. A rightward parallel shift in the concentration-response curve for GABA was observed in the presence of histamine, without substantial change in the maximal response or the Hill coefficient. Results were compatible with a competitive antagonism of histamine on the GABAAρ1 receptors. This is the first report of inhibitory actions exerted by histamine on an ionotropic GABA receptor.

How to choose an antihistamine drug for patients of special groups?

The authors of the article describe the dependence of the effectiveness of any drug on the "correctness" of its choice for the patient and conclude that patient profiling can serve as an effective clinical method for selecting optimal therapy. When prescribing antihistamines, it is suggested to use the following main patient profiles: children, working adults, elderly patients. Each profile has its own specific purpose. The article presents own clinical experience of using fexofenadine based on patient profiling. Cases of fexofenadine therapy in patients with allergic rhinitis and chronic urticaria are given as specific examples. Fexofenadine has an optimal safety profile with minimal impact on concentration and cognitive abilities. In this regard, it can be recommended to employees whose activities are associated with the speed of psychomotor reactions, schoolchildren and university students, elderly patients with high drug load and comorbidity.

Dystocia due to a dicephalus monster fetus in a buffalo and It's successful per vaginal removal

Fetal anomalies and monstrosities are common causesof dystocia in bovines and are disturbances of development that involve the sexual organs and cause great distortion of the individual. The incidence of abnormal calvings in buffaloes is from 4.6% to 12.6%. Eight years aged native buffalo, with its third lactation with ahistory of natural service 306 days back was presented to the Veterinary Hospital, Hombal Village, Gadag taluk of Gadag district, Karnataka State. The animal was presented with the complaintof inspite of continuous straining for the last 06 h after the expulsion of the first water bag, there was no progression to the parturition stage. Pervagina lexamination reveale dafully dilatedcervix and abnormal fetus with two heads joined at the neck in anterior presentation with dorsolateral position witha deviation ofhead, one head was removed gently followed by anotherthat was 90-degree angle corrected and removed a female dead fetus under low caudal epidural anaesthesia. Adicephalusmonsterfetus was relieved pervaginally without surgicalintervention and reported. Post operative care consisted of intravenousantibiotics, fluids intra muscular anti-inflammatory and anti-histamine drugs for seven days.The buffalo hadan uneventful recovery.

General Synthesis of 3‐Azabicyclo[3.1.1]heptanes and Evaluation of Their Properties as Saturated Isosteres**

AbstractA general approach to 3‐azabicyclo[3.1.1]heptanes by reduction of spirocyclic oxetanyl nitriles was developed. The mechanism, scope, and scalability of this transformation were studied. The core was incorporated into the structure of the antihistamine drug Rupatidine instead of the pyridine ring, which led to a dramatic improvement in physicochemical properties.