Histamine H1 Antagonists Research Articles

Quantitative estimation of doxylamine succinate by zero-order derivative area under curve Spectrophotometric methods in bulk and in-tablet dosage form

The purpose of this study is to establish Zero-order UV-Spectrophotometric - absorbance and Zero Order- Area under curve (AUC) methods for estimation of Doxylamine succinate in bulk and in pharmaceutical dosage form . Doxylamine succinate is Histamine H1 antagonist with pronounced sedative properties. It is used in allergies and as an antitussive, antiemetic, and hypnotic. Doxylamine has also been administered in veterinary applications and was formerly used in parkinsonism, distilled water was used as solvent for solubilization of Doxylamine succinate. Maximum absorption for Doxylamine succinate was found to be at wavelength 260nm when dissolved in Distilled water. The methods are based upon measurement of absorbance at 260nm and integration of area under curve for analysis of Doxylamine succinate in the wavelength range of 251.20-267.20 nm. The drug followed linearity in the concentration range of 10 - 60µg/mL with correlation coefficient value r> 0.99 . The proposed methods were validated for accuracy (% recovery), precision, repeatability and ruggedness, as per ICH guidelines. The proposed methods were applied for qualitative and quantitative estimation of Doxylamine succinate in tablet and results were found in good agreement with the label claimed. Developed methods can be used for routine analysis of Doxylamine succinate in bulk and pharmaceutical tablet.

Neuroprotective Effect of Clemastine Improved Oligodendrocyte Proliferation through the MAPK/ERK Pathway in a Neonatal Hypoxia Ischemia Rat Model.

Neonatal hypoxic-ischemic encephalopathy is the most common cause of long-term disability in term neonates, and white matter injury is the primary cause of cerebral palsy. Therapies that focus on the neuroprotection of myelination and oligodendrocyte proliferation could potentially ameliorate long-lasting neurological impairments after hypoxic-ischemic encephalopathy. Clemastine, a histamine H1 antagonist, has been shown to exert neuroprotective effects in multiple sclerosis and spinal cord injury by promoting oligodendrogenesis and re-myelination. In this study, we demonstrated the neuroprotective effects of clemastine in our rat model of neonatal hypoxic-ischemic brain injury. Animals received a single intraperitoneal injection of either vehicle or clemastine (10 mg/kg) for 6 consecutive days. Our results showed a significant reduction in white matter loss after treatment, with a clear effect of clemastine on oligodendrocytes, showing a significant increase in the number of Olig2+ cells. We characterized the MAPK/ERK pathway as a potential mechanistic pathway underlying the neuroprotective effects of clemastine. Altogether, our results demonstrate that clemastine is a potential compound for the treatment of hypoxic-ischemic encephalopathy, with a clear neuroprotective effect on white matter injury by promoting oligodendrogenesis.

Cost analysis study of price variation among the various brands of proton pump inhibitors available in Benghazi-Libya

Background: A large proportion of patients in developing countries have to pay out of pocket for their medications. The prices of different brands of the same medications vary considerably and may vary from one community pharmacy to another. This study was undertaken to evaluate the variation in costs of proton pump inhibitors (PPI) and histamine H2-receptor antagonists available in Libya. Methods: Prices of various brands of PPI and various formulations were collected from four community pharmacies in the city of Benghazi. Both cost ratio and percentage variation were calculated and compared for various brands of the same strength and number of tablets, capsules, injections, or syrups. Results: The highest cost ratio and percentage price variation were found with omeprazole 20 mg, followed by omeprazole 40 mg. Other significant cost variations (>100%) were seen with pantoprazole 40 mg, Downoprazol (omeprazole + sodium bicarbonate) 40 mg, and esomeprazole 40 mg. Ampoules of omeprazole, cimetidine, and ranitidine had cost ratios of 1:1.7, 1:1.7, and 1:1.8, and cost variation ratios of 71.4, 66.7, and 75, respectively. Variations in prices of PPI and histamine H2 antagonists from the same manufacturer between different community pharmacies were common. The highest percentage cost variation (100) was seen with omeprazole 20 mg. Conclusions: Due to political instability, the prices of all drugs are controlled by importing private companies and the owners of community pharmacies instead of governmental authorities, that leads to cost variations. Therefore, the health authorities exert strict control on pricing of medications.

Green HPLC–DAD method for the analysis of analgesic and antihistamine drugs adulterated in herbal mixtures

This study presents a HPLC-DAD method developed for the simultaneous detection of histamine H1 antagonist drugs and analgesic compounds, including paracetamol, cetirizine hydrochloride, cinnarizine, chlorpheniramine maleate, and loratadine, in herbal formulations. This method systematically investigates critical parameters for enhancing separation and quantification using HPLC-DAD. Chemometric techniques were employed to optimize the method for detecting adulterants, with sample preparation involving liquid-phase extraction and a mobile phase for separation using HPLC-DAD. The calibration curves were linear over concentrations ranging from 10 to 40 µg/mL, with correlation coefficients exceeding 0.99. The method exhibits good accuracy, with mean recoveries ranging from 90 to 105 %, and precision (% RSD) for intraday and interday precision: 0.71 to 2.94 %. The limits of detection (LODs) and limits of quantification (LOQs) for each compound are provided. The HPLC-DAD method ensures rigorous quality control, detecting potential adulteration in 32 traditional medicine samples and emphasizing its safety and efficacy in managing allergic conditions. The proposed approach is considered environmentally friendly based on evaluations from commonly used greenness assessment tools, Green analytical chemistry metrics (ComplexGAPI, AGREE, BAGI) confirm the method's sustainability and practicality.

Emerging strategies for treating autoimmune disorders in patients with type 1 diabetes and multiple sclerosis

In the world as a whole and in Ukraine in partmicular, the incidence of autoimmune pathologies continues to grow steadily. There is an increase in the number of type 1 diabetes mellitus (T1DM) and multiple sclerosis (MS) cases in the population. Both diseases have an autoimmune nature and several common features in terms of onset, diagnosis, lack of effective treatment and deve­lopment of complications that are potentially life-threatening. In addition, both diseases have genetic risk factors associated with human leukocyte antigen. There are also other genetic risk factors, such as T-cell alleles of interleukin-2 and protein tyrosine phosphatase, non-receptor type 22 in MS and T1DM, respectively. The environment also plays a significant role in the development of both diseases, with smoking and exposure to viruses increasing the risk of MS and T1DM. To date, the proposed methods of therapy for both diseases are not completely effective, and some of them even have serious side effects. The authors consider the possibility of using clemastine fumarate as a histamine H1 antagonist in the management of T1DM and MS. This histamine H1 antagonist penetrates the blood-brain barrier more easily and thus leads to a sedative effect. The efficacy of clemastine fumarate to enhance remyelination in MS was recently demonstrated in a double-blind crossover clinical trial. In addition, this compound was effective in the treatment of T1DM and its complications in a number of experimental studies. The currently available data allow us to recommend clemastine fumarate as the drug of choice in the comprehensive management of patients with MS. Attention is focused on the need for clinical studies to prove the effectiveness of clemastine fumarate in the treatment of patients with T1DM.

Update meta-analysis on the efficacy and safety issues of fexofenadine

BackgroundFexofenadine emerged as one of the most representative second generation histamine H1 antagonist drugs since the 1990s, with an outstanding efficacy and appreciable safety for the treatment of allergic patients. While allergic rhino-conjunctivitis represents the most frequent atopic disease globally, an update of fexofenadine efficacy and safety on this entity was proposed as a surrogate of allergic condition. MethodsDouble blind, placebo controlled, randomized clinical trials investigating the efficacy and safety of fexofenadine for the treatment of Allergic Rhinitis were searched in 5 major global databases. Eligibility criteria and characteristics, risk of bias, and validity assessment, data extraction and heterogeneity evaluation are described. Primary outcome selected corresponded to 12-reflective and instantaneous total symptom scores (TSS), besides morning instantaneous TSS and the frequency of reported adverse events (AEs); analysis was planned on the intention-to-treat population.Standardized mean differences of scoring systems were analyzed, and Cochran's Q statistic test and the I2 test were assessed for heterogeneity. ResultsFrom the initial 83 identified records, 12 eligible studies were selected. In the evaluated patients, individuals receiving fexofenadine (1910) showed a significant reduction of TSS compared with those who received placebo (1777), change from baseline: standardized mean difference (SMD) –0.33; 95% CI–0.47 to −0.18, p < 0.0001. Morning instantaneous TSS also demonstrated lower symptoms (change from baseline: SMS -1.42; 95% CI -2.22 to −0.62, p = 0.0005). Heterogeneity was found across selected studies.Frequency of AEs was similar compared to placebo (OR = 1.04; 0.88–1.21), with no detection of heterogeneity across these 12 studies. ConclusionsAccording to this new evidence, fexofenadine maintains its beneficial profile on signs and symptoms of patients with allergic conditions, as well as its attributes as one of the major candidates for an ideal antihistamine medication (including special conditions such as pregnancy and pre-school age), providing support to its over-the-counter condition in several countries.

Epigenetic Histone Methylation of PPARγ and CPT1A Signaling Contributes to Betahistine Preventing Olanzapine-Induced Dyslipidemia.

As a partial histamine H1 receptor agonist and H3 antagonist, betahistine has been reported to partially prevent olanzapine-induced dyslipidemia and obesity through a combination therapy, although the underlying epigenetic mechanisms are still not known. Recent studies have revealed that histone regulation of key genes for lipogenesis and adipogenesis in the liver is one of the crucial mechanisms for olanzapine-induced metabolic disorders. This study investigated the role of epigenetic histone regulation in betahistine co-treatment preventing dyslipidemia and fatty liver caused by chronic olanzapine treatment in a rat model. In addition to abnormal lipid metabolism, the upregulation of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein (C/EBPα), as well as the downregulation of carnitine palmitoyltransferase 1A (CPT1A) in the liver induced by olanzapine, were significantly attenuated by betahistine co-treatment. In addition, betahistine co-treatment significantly enhanced the global expression of H3K4me and the enrichment of H3K4me binding on the promoter of Cpt1a gene as revealed by ChIP-qPCR, but inhibited the expression of one of its site-specific demethylases, lysine (K)-specific demethylase 1A (KDM1A). Betahistine co-treatment also significantly enhanced the global expression of H3K9me and the enrichment of H3K9me binding on the promoter of the Pparg gene, but inhibited the expression of two of its site-specific demethylases, lysine demethylase 4B (KDM4B) and PHD finger protein 2 (PHF2). These results suggest that betahistine attenuates abnormal adipogenesis and lipogenesis triggered by olanzapine through modulating hepatic histone methylation, and thus inhibiting the PPARγ pathway-mediated lipid storage, while at the same time promoting CP1A-mediated fatty acid oxidation.

Histamine and its H1 receptors in the ventral pallidum mediate formalin-induced pain-related behaviors through this region and spinal cord opioid receptors.

Many structures of the central nervous system recruit different neurotransmitters in pain processing. This study focused on the contribution of histamine and its H1 receptors in the ventral pallidum (VP) in mediating pain-triggered behaviors. Intra-VP microinjection of histamine and 2-pyridylethylamine (2-PEA, a histamine H1 receptor agonist) at the same doses of 0.5 and 1 µg/200 nl reduced both the first and second phases of licking/biting duration as well as flinching number induced by intra-plantar (ipl) injection of formalin (2.5%, 50 µl). Premicroinjection of mepyramine (a histamine H1 antagonist, 2 µg/200 nl) into the VP antagonized the suppressive effects of 1 µg/200 nl histamine and 2-PEA on licking/biting and flinching behaviors. The possible mechanisms of the above-mentioned pain-reducing effects were followed by intra-VP and intrathecal administration of naloxone (an opioid receptor antagonist). Naloxone (2 µg/200 nl) preadministration into the VP inhibited attenuating effects of histamine and 2-PEA on both the licking/biting and flinching behaviors, whereas intrathecal injection of naloxone only inhibited their suppressing effects on flinching behavior. None of the treatments used in this study altered the animal's motor activity. The obtained results may reveal the role of histamine and its activated H1 receptor in the VP in suppressing the pain behaviors caused by formalin. Opioid receptors in the VP and spinal cord may contribute to these functions.

Green Solvents for Eco-Friendly Synthesis of Dimethindene: A Forward-Looking Approach.

Dimethindene is a selective histamine H1 antagonist and is commercially available as a racemate. Upon analyzing the synthetic pathways currently available for the industrial preparation of dimethindene, we set up a sustainable approach for the synthesis of this drug, switching from petroleum-based volatile organic compounds (VOCs) to eco-friendly solvents, such as 2-methyltetrahydrofuran (2-MeTHF) and cyclopentyl methyl ether (CPME) belonging to classes 3 and 2, respectively. Beyond decreasing the environmental impact of the synthesis (E-factor: 24.1-54.9 with VOCs; 12.2-22.1 with 2-MeTHF or CPME), this switch also improved the overall yield of the process (from 10% with VOCs to 21-22% with 2-MeTHF or CPME) and remarkably simplified the manual operations, working under milder conditions. Typical metrics applied at the first and second pass, according to the CHEM21 metrics toolkit, were also calculated for the whole synthetic procedure of dimethindene, and the results were compared with those of the classical procedure.

Solubility Enhancement of Ebastine by Formulating Microemulsion Using D-Optimal Mixture Design: Optimization and Characterization.

Ebastine, a histamine H1 antagonist, nonsedating, belonging to BCS class II is used in the treatment of allergic rhinitis and chronic idiopathic urticaria. The current study was intended in augmenting the aqueous solubility and dissolution rate of ebastine, by formulating a microemulsion system using oleic acid, Transcutol® HP, and Tween®80 as oily phase, cosurfactant, and surfactant, respectively, by the phase titration method. A custom mixture design with optimality D was used to design the formulation by using the Design Expert® Software (Version 11; Stat-Ease, Inc., Minneapolis, MN, USA). Optimization of formulation was performed using the numerical optimization technique, where optimization is based upon the desirability. The optimized formulation was evaluated for transmittance, viscosity, globule size, polydispersity index, zeta potential, drug content, morphological studies, and in vitro studies. The optimized formulation displayed percent cumulative drug release, ranging from 82.9% to 90.6% obtained after dissolution studies and the percent cumulative drug release after diffusion studies ranged from 83.3% to 100%. The in vitro release data were subjected to kinetic treatment. The zero-order and first-order plots were linear and showed the highest values for R2, which indicated mixed-order release. The Higuchi plot was linear, indicating diffusion as the mechanism of release. From Peppas plot, it was further confirmed that the release for dissolution studies was anomalous and for diffusion studies it was zero order. Thus, the studies concluded that the microemulsion technique is a very good approach for enhancing the solubility and dissolution rate of the BCS class II drug ebastine.

Mucoprotectants

The gastric mucosa is constantly exposed to gastric acid and pepsin. Moreover, various factors, such as nonsteroidal anti-inflammatory drugs, &lt;i&gt;Helicobacter pylori&lt;/i&gt; infection, ethanol, stress, and aging, can damage the gastrointestinal mucosa. Nevertheless, even under these harsh conditions, the gastric mucosa is structurally maintained by various processes, referred to as “defense mechanisms.” Mucosal defense mechanisms are complicated; however, the most important elements are known to be the gastric epithelium and mucus layer, which are stimulated by prostaglandins and nitric oxide. Peptic ulcers result from an imbalance between these aggressive and defensive factors. Methods to prevent or treat peptic ulcers can be classified into two classes: 1) inhibition of gastric acid secretion and 2) promotion of mucosal defense factors. Drugs that reduce gastric acid secretion include proton pump inhibitors, histamine H2 antagonists, and potassium-competitive acid blockers. Mucoprotectants prevent peptic ulcers by promoting peptic ulcer healing. Mucoprotectants can work by two main mechanisms of action; one is independent of prostaglandins, and the other is related to prostaglandin activity. Bismuth, sucralfate, and misoprostol have been traditionally used to protect the gastric mucosa from gastric acid and pepsin. Currently, several mucoprotectants, such as rebamipide, ecabet sodium, polaprezinc, teprenone, and DA-9601, are prescribed in clinical practice. This review aims to provide information to clinicians by examining the characteristics of each drug, including their mechanism of action, research results, effective dose, and side effects.

Clemastine Induces an Impairment in Developmental Myelination.

Abnormalities in myelination are associated to behavioral and cognitive dysfunction in neurodevelopmental psychiatric disorders. Thus, therapies to promote or accelerate myelination could potentially ameliorate symptoms in autism. Clemastine, a histamine H1 antagonist with anticholinergic properties against muscarinic M1 receptor, is the most promising drug with promyelinating properties. Clemastine penetrates the blood brain barrier efficiently and promotes remyelination in different animal models of neurodegeneration including multiple sclerosis, ischemia and Alzheimer’s disease. However, its role in myelination during development is unknown. We showed that clemastine treatment during development increased oligodendrocyte differentiation in both white and gray matter. However, despite the increase in the number of oligodendrocytes, conduction velocity of myelinated fibers of corpus callosum decreased in clemastine treated mice. Confocal and electron microscopy showed a reduction in the number of myelinated axons and nodes of Ranvier and a reduction of myelin thickness in corpus callosum. To understand the mechanisms leading to myelin formation impairment in the presence of an excess of myelinating oligodendrocytes, we focused on microglial cells that also express muscarinic M1 receptors. Importantly, the population of CD11c+ microglia cells, necessary for myelination, as well as the levels of insulin growth factor-1 decrease in clemastine-treated mice. Altogether, these data suggest that clemastine impact on myelin development is more complex than previously thought and could be dependent on microglia-oligodendrocyte crosstalk. Further studies are needed to clarify the role of microglia cells on developmental myelination.

Isolation, Characterisation and Evaluation of Antiulcerogenic Potentials of Probiotic Lactic Acid Bacteria Isolated from Fermented Milk and Palm Wine against Ethanol-Induced Gastric Ulcer in Mice

Background: Gastric ulcer is one of the most common gastrointestinal diseases with a worldwide prevalence of about 40% in the developed countries and 80% in Africa. Acid inhibitors, anticholinergics, histamine H2-antagonists and antibiotics are commonly used to treat gastric ulcer. However, the accumulating evidence for resistance to antibiotics and the side effects of antibiotics and acid inhibitors, anticholinergics and histamine H2-antagonists. Therefore, there is an urgent need for approaches to treat and prevent gastric ulcer. One alternative strategy is the use of probiotic lactic acid bacteria. Aim of the study: This study aimed to isolate and characterised probiotic lactic acid bacteria from palm wine and fermented milk, and to evaluate their antiulcerogenic potentials on ethanol-induced gastric ulcer in mice. Methods: Probiotic lactic acid bacteria were isolated from the fermented milk and palm wine using pour plate technique on MRS agar and identified using the 16S r RNA gene sequencing. For functional properties and selection, acid and bile salt tolerance were evaluated based on viable colony count on MRS agar. Two probiotic lactic acid bacteria were selected for in vivo studies. Fifty-four healthy young adult Balb/c mice were randomly divided into 9 groups of 6 mice each. Gastric ulcer was induced in mice using one oral dose of absolute ethanol (10 mL/kg body weight). The probiotic lactic acid bacteria (F1 and F2) at different doses (MF3 = 9 × 108 CFU/mL, MF6 = 1.8 × 109 CFU/mL and MF9 = 2.7 × 109 CFU/mL) and omeprazole (20 mg/kg) (a reference drug) were orally administrated daily for 14 days before ulcer induction. These mice were sacrificed 1hour after induction and the stomach contents were collected for volume and pH determination. The stomachs were subjected to macroscopic, biochemical and histopathological analysis. Results: Among the isolates obtained, two were considered to have the best acid and bile tolerance capacity (viable count > 7.5 logCFU/ml) and were identified as Limosilactobacillus fermentum strain BB101 (F1) and Lactobacillus casei strain 02 (F2). Oral administration of probiotics Lactic acid bacteria F1 and F2 significantly attenuated gastric ulcer as revealed by significant reduction (P lactobacillus fermentum strain BB101 and Lactobacillus casei 02 with excellent bile and acid tolerance capacity. Also, these probiotic lactic acid bacteria exhibit gastroprotective effect on ethanol-induced gastric ulcer via antioxidant, enhance gastric ulcer healing, antacids, and anti-secretary effects.

Structures 4-n-propyl Piperazines as Non-Imidazole Histamine H3 Antagonists.

Seven new low-temperature structures of 4-n-propylpiperazine derivatives, potential H3 receptor antagonists, have been determined by X-ray crystallography, with the following symmetry and unit cell parameters: 2-(4-propyl-piperazin-1-yl)oxazolo[4,5-c]pyridine (compound 1), P-1, 5.9496 Å, 12.4570 Å, 12.8656 Å, 112.445°, 95.687°, 103.040°; 2-(4-propyl-piperazin-1-yl)thia-zolo[4,5-c]pyridine (compound 2), I2/a, 22.2087 Å, 7.5519 Å, 19.9225 Å, β = 92.368°; 2-(4-propyl-piperazin-1-yl)oxazolo[5,4-c]pyridine (compound 3), C2/c, 51.1351 Å, 9.36026 Å, 7.19352 Å, β = 93.882°; 2-(4-propyl-piperazin-1-yl)thiazolo[5,4-c]pyridine (compound 4), Pbcn, 19.2189 Å, 20.6172 Å, 7.4439 Å; 2-(4-propylpiperazin-1-yl)[1,3]oxazolo[4,5-b]pyridine, hydrate (structure 5), Pbca, 7.4967 Å, 12.2531 Å, 36.9527 Å; 2-(4-propylpiperazin-1-yl)[1,3]oxazolo[4,5-b]pyridine, first polymorph (structure 6), P-1, 7.2634 Å, 11.1261 Å, 18.5460 Å, 80.561°, 80.848°, 76.840°; 2-(4-propylpiperazin-1-yl)[1,3]oxazolo[4,5-b]pyridine, second polymorph (structure 7), P21, 8.10852 Å, 7.06025 Å, 12.41650 Å, β = 92.2991°. All the compounds crystallized out as hydrobromides. Oxazole structures show a much greater tendency to form twin crystals than thiazole structures. All the investigated structures display N—H···Br hydrogen bonding. (ADME) analysis, including the assessment of absorption, distribution, metabolism, and excretion, determined the physicochemical properties, pharmacokinetics, drug similarity, and bioavailability radar, and confirmed the usefulness of the compounds in question for pharmaceutical utility. This work is a continuation of the research searching for a new lead of non-imidazole histamine H3 receptor antagonists.

An Update on Assessment, Therapeutic Management, and Patents on Insomnia.

Insomnia is an ordinary situation related to noticeable disability in function and quality of life, mental and actual sickness, and mishappenings. It represents more than 5.5 million appointments to family doctors every year. Nonetheless, the ratio of insomniacs who are treated keeps on being low, demonstrating the requirement for proceeding with advancement and dispersal of effective treatments. Accordingly, it becomes significant to provide a compelling treatment for clinical practice. It indicates a need for the determination of various critical viewpoints for the evaluation of insomnia along with various accessible alternatives for treatment. These alternatives incorporate both nonpharmacological therapy, specifically cognitive behavioural therapy for insomnia, and a number of pharmacological treatments like orexin antagonists, “z-drugs,” benzodiazepines, selective histamine H1 antagonists, nonselective antihistamines, melatonin receptor agonists, antipsychotics, antidepressants, and anticonvulsants. Besides in individuals whose insomnia is due to restless leg syndrome, depression/mood disorder, or/and circadian disturbance, there is insignificant proof favouring the effectiveness of different prescriptions for the treatment of insomnia though they are widely used. Other pharmacological agents producing sedation should be prescribed with care for insomnia therapy because of greater risk of next-day sleepiness along with known adverse effects and toxicities. This review is also aimed at providing an update on various patents on dosage forms containing drugs for insomnia therapy.

Innovative Method Development Comprehensive Separation of Impurities and Validation for a novel Antipsychotic Drug Blonanserin

Blonanserin an antipsychotic novel drug used for the treatment of schizophrenia has antagonist properties for dopamine D2 and serotonin 5-HT2. On the other hand, it lacks adrenergic-α1, muscarinic M1, and histamine H1 antagonist activities. Clinical studies demonstrated in Japan had shown to be more effective for treating negative as well as positive schizophrenic symptoms. This drug was accepted and approved worldwide in the treatment of schizophrenia. A new HPLC method was developed and validated for the estimation of Impurities of Blonanserin (BNS) to ensure that the methodology meets the requirements of the target analysis application. Active and efficient chromatographic separation was achieved on a Zorbax Bonus RP EP C18 column having a particle size of 5μm, with dimensions of 250mm × 4.6 mm, mobile phase containing pH 2.4 buffer and Organic, with 1.0 ml /min flow rate, column oven temperature at 30oC and the eluent detection at 245 nm. The method shows well-separated impurities, is specific without interference from blank solution with resolution more than 1.2 between any of the impurity, correlation coefficient more than 0.99 showing good linearity; mean recovery ranging from 97% to 105% and is very sensitive at lower detection and quantification limits. This method was well developed and has been applied successfully to monitor and estimate impurities in Blonanserin.

Testing of the inhibitory effects of loratadine and desloratadine on SARS-CoV-2 spike pseudotyped virus viropexis

Currently, there is an urgent need to find a treatment for the highly infectious coronavirus disease (COVID-19). However, the development of a new, effective, and safe vaccine or drug often requires years and poses great risks. At this critical stage, there is an advantage in using existing clinically approved drugs to treat COVID-19. In this study, in vitro severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike pseudotyped viral infection experiments indicated that histamine H1 antagonists loratadine (LOR) and desloratadine (DES) could prevent entry of the pseudotyped virus into ACE2-overexpressing HEK293T cells and showed that DES was more effective. Further binding experiments using cell membrane chromatography and surface plasmon resonance demonstrated that both antagonists could bind to ACE2 and that the binding affinity of DES was much stronger than that of LOR. Molecular docking results elucidated that LOR and DES could bind to ACE2 on the interface of the SARS-CoV-2-binding area. Additionally, DES could form one hydrogen bond with LYS31 but LOR binding relied on non-hydrogen bonds. To our knowledge, this study is the first to demonstrate the inhibitory effect of LOR and DES on SARS-CoV-2 spike pseudotyped virus viropexis by blocking spike protein–ACE2 interaction. This study may provide a new strategy for finding an effective therapeutic option for COVID-19.

Cognitive impairment under treatment with second‐ and third‐generation antihistamines

AbstractBackgroundBrain histamine is involved in the regulation of arousal, cognition, and memory mainly through interactions with histamine H1 receptors. Histamine H1 antagonists often prescribed for treatment of allergic disorders, may induce sleepiness and cognitive deficits. Sedation as a consequence of treatment with 1st generation antihistamines has led to the development of 2nd and 3rd generation anthistamines, which are thought to be free of cognitive side effects. This proved to be true in studies on the cognitive effects of single doses in healthy volunteers. However, the relationship between treatment with 2nd or 3rd generation antihistamines and cognitive performance so fas has not been examined within a naturalistic study under everyday conditions. This may be relevant for Alzheimer’s disease treatment studies, because cognitive side effects as a consequence of treatment with 2nd or 3rd generation antihistamines may act as a confounding variable.Method380 patients with chronic spontaneous urticaria (CSU) were assessed in 30 dermatological practices and outpatient clinics in Germany. Severity of disease was assessed by means of the Urticaria Activity Score (UAS‐7) and the Urticaria Control Test (UCT), quality of life by the Dermatology Life Quality Index (DLQI) and the Chronic Urticaria Quality of Life Questionnaire (CU‐Q2oL). Cognitive performance was studied by means of the computer‐based Memory and Attention Test (MAT). Sociodemographic data, current medication in treatment categories, comorbidities, obesity, smoking and drinking habits are taken by a questionnaire.ResultThe assessments were carried out in 380 subjects at ages between 19 and 73 years (mean +/‐ SD: 49 +/‐ 15). In patients under treatment with 2nd or 3rd generation anthistamines compared to patients not under treatment with antihistamines, we found a significant impairment of episodic working memory, particularly in the elder subjects. The impairment was found independently whether antihistamines were applied at dosages licensed for treatment or at higher dosages. Episodic short‐term memory and selective attention were unimpaired.ConclusionTreatment with 2nd or 3rd generation antihistamines may be associated with cognitive impairment, particularly in elderly patients. This effect should be considered regarding the handling of concomitant medications in Alzheimer’s disease treatment trials.

Effects of uncomfortable care and histamine H2-antagonists on delirium in acute stroke: A propensity score analysis

Background and purposeUncomfortable care and histamine H2 antagonist (H2A) are implicated in precipitating delirium. In acute stroke, however, the need for them depends on stroke severity, an established risk factor for delirium. So, it is unclear whether care or H2A itself is responsible for delirium. We aimed to evaluate their causal effects on delirium in acute stroke patients. MethodsThis is a prospective cohort study on acute stroke patients admitted to a stroke care unit. Patients without stupor, coma, sedation, or delirium upon admission were enrolled. The treatment was H2A and five care modalities given during the first 24 h: restraint use, prohibited self-transfer, no oral feeding, indwelling catheters, and frequent nighttime care. The outcome was delirium within 5 days defined as Intensive Care Delirium Screening Checklist ≥4 points. We estimated the relative risk (RR) for delirium with regression models weighted by overlap weights using propensity scores estimated through logistic models incorporating known and potential confounders, including stroke severity. ResultsOf the 387 participants, 188 were given at least one care modality and 130 were given H2A. A total of 42 developed delirium. Delirium was significantly associated with prohibited self-transfer (RR 1.7, 95% CI 1.0–3.0), frequent nighttime care (RR 2.1, 95% CI 1.2–3.7), and multiple care modalities (RR 2.4, 95% CI 1.3–4.4), while other care modalities and H2A were not. ConclusionsThis study showed possible causal effects of uncomfortable care on delirium and suggests that minimizing it could prevent delirium in acute stroke.

Sir James Whyte Black OM. 14 June 1924—22 March 2010

James Whyte Black was a Scottish pharmacologist who trained in medicine at St Andrews University and had a career in drug invention and academic pharmacology, moving several times between universities and the pharmaceutical industry. He was awarded the 1988 Nobel Prize in Physiology or Medicine for his drug invention method, which was to build molecules around the structure of a natural chemical activator of a pathway involved in the aetiology of a disease. This produced two extremely useful drug categories, beta-blockers and histamine H 2 -antagonists, with huge impact on the previously intractable diseases of angina, hypertension and stomach ulcers. In 2000 he was awarded the UK's highest honour, the Order of Merit (OM). His ideas on analytical pharmacology had a significant effect on the development of the discipline in the late twentieth century.