Chemoinformatic Analysis of Psychotropic and Antihistaminic Drugs in the Light of Experimental Anti-SARS-CoV-2 Activities

<div> <div> <div><b>Introduction:</b> There is an urgent need to identify therapies that prevent SARS-CoV-2 infection and improve the outcome of COVID-19 patients. <p><b>Objective:</b> We proposed, before summer 2020, that cationic amphiphilic psychotropic and antihistaminic drugs could protect psychiatric patients from SARS-CoV-2 infection based upon clinical observations. At that time, experimental in vitro data on SARS-CoV-2 were missing.</p> <p><b>Methods:</b> Open high-throughput screening results are now available at the NCATS COVID-19 portal and it is possible to investigate again our initial hypothesis using simple chemoinformatics approaches but this time with in vitro data on SARS-CoV-2.</p> <p><b>Results and Discussion:</b> We here revisit our initial hypothesis in the light of SARS-CoV-2 experimental screening results and propose that several cationic amphiphilic psychotropic and antihistaminic drugs could protect people from SARS-CoV-2 infection; some of these molecules have very limited adverse effects and could eventually be used as prophylactic drugs. Further, recent analyses of electronic health records reported by several research groups, including drug combinations, indicate that a small list of molecules could be of interest at different stages of the disease progression. Taken together, these observations suggest that clinical trials are now needed to fully evaluate the potentials of these potential small molecules broad-spectrum antiviral agents. Orally available drugs would indeed be of outmost importance to deal with COVID-19.</p> </div> </div> </div>

Chemoinformatic Analysis of Psychotropic and Antihistaminic Drugs in the Light of Experimental Anti-SARS-CoV-2 Activities

<div> <div> <div><b>Introduction:</b> There is an urgent need to identify therapies that prevent SARS-CoV-2 infection and improve the outcome of COVID-19 patients. <p><b>Objective:</b> We proposed, before summer 2020, that cationic amphiphilic psychotropic and antihistaminic drugs could protect psychiatric patients from SARS-CoV-2 infection based upon clinical observations. At that time, experimental in vitro data on SARS-CoV-2 were missing.</p> <p><b>Methods:</b> Open high-throughput screening results are now available at the NCATS COVID-19 portal and it is possible to investigate again our initial hypothesis using simple chemoinformatics approaches but this time with in vitro data on SARS-CoV-2.</p> <p><b>Results and Discussion:</b> We here revisit our initial hypothesis in the light of SARS-CoV-2 experimental screening results and propose that several cationic amphiphilic psychotropic and antihistaminic drugs could protect people from SARS-CoV-2 infection; some of these molecules have very limited adverse effects and could eventually be used as prophylactic drugs. Further, recent analyses of electronic health records reported by several research groups, including drug combinations, indicate that a small list of molecules could be of interest at different stages of the disease progression. Taken together, these observations suggest that clinical trials are now needed to fully evaluate the potentials of these potential small molecules broad-spectrum antiviral agents. Orally available drugs would indeed be of outmost importance to deal with COVID-19.</p> </div> </div> </div>

Chemoinformatic Analysis of Psychotropic and Antihistaminic Drugs in the Light of Experimental Anti-SARS-CoV-2 Activities

<div> <div> <div><b>Introduction:</b> There is an urgent need to identify therapies that prevent SARS-CoV-2 infection and improve the outcome of COVID-19 patients. <p><b>Objective:</b> We proposed, before summer 2020, that cationic amphiphilic psychotropic and antihistaminic drugs could protect psychiatric patients from SARS-CoV-2 infection based upon clinical observations. At that time, experimental in vitro data on SARS-CoV-2 were missing.</p> <p><b>Methods:</b> Open high-throughput screening results are now available at the NCATS COVID19 portal and it is possible to investigate again our initial hypothesis using simple chemoinformatics approaches but this time with in vitro data on SARS-CoV-2.</p> <p><b>Results and Discussion:</b> We here revisit our hypothesis in the light of SARS-CoV-2 experimental screening results and propose that several cationic amphiphilic psychotropic and antihistaminic drugs could possibly protect people from SARS-CoV-2 infection; some of these molecules have very limited adverse effects and could eventually be used as prophylactic drugs. Further, recent analysis of electronic health records reported by other research groups, including drug combinations, also suggest that a small list of molecules could be of interest at different stages of the disease progression. Taken together, these observations suggest that clinical trials are now needed to fully evaluate the potentials of these molecules.</p> </div> </div> </div>

Chemoinformatic Analysis of Psychotropic and Antihistaminic Drugs in the Light of Experimental Anti-SARS-CoV-2 Activities

<div> <div> <div> <p>There is an urgent need to identify therapies that prevent SARS-CoV-2 infection and improve the outcome of COVID-19 patients. We proposed before summer 2020 that cationic amphiphilic psychotropic and antihistaminic drugs could protect psychiatric patients from SARS-CoV-2 infection based upon clinical observations. At that time, experimental data on SARS-CoV-2 were missing but today, open high-throughput screening results are available at the NCATS COVID19 portal. We here revisit our hypothesis in the light of these data and propose that several cationic amphiphilic psychotropic and antihistaminic drugs could be valuable to protect people from SARS-CoV-2 infection, they should have very limited adverse effects and could possibly be used as prophylactic drugs. Recent studies also suggest that some of these molecules could be of interest in more advanced stages of the disease progression. Clinical trials are now needed to fully evaluate the potentials of these molecules. </p> </div> </div> </div>

Chemoinformatic Analysis of Psychotropic and Antihistaminic Drugs in the Light of Experimental Anti-SARS-CoV-2 Activities

<div> <div> <div> <p>There is an urgent need to identify therapies that prevent SARS-CoV-2 infection and improve the outcome of COVID-19 patients. We proposed before summer 2020 that cationic amphiphilic psychotropic and antihistaminic drugs could protect psychiatric patients from SARS-CoV-2 infection based upon clinical observations. At that time, experimental data on SARS-CoV-2 were missing but today, open high-throughput screening results are available at the NCATS COVID19 portal. We here revisit our hypothesis in the light of these data and we propose that several cationic amphiphilic psychotropic and antihistaminic drugs could be valuable to protect people from SARS-CoV-2 infection, they should have very limited adverse effects and could possibly be used as prophylactic drugs. Recent studies also suggest that some of these molecules could be valuable in more advanced stages of the disease progression. Clinical trials are now needed to fully evaluate the potentials of these molecules. </p> </div> </div> </div>

D-dimer concentrations in acute urticaria in children

Introduction: Urticaria is a clinical entity presenting as wheals, angioedema, or both simul-taneously. Elevated D-dimer levels were reported in the course of chronic spontaneous urticaria. Data regarding D-dimer levels in acute urticaria in children are limited. Objectives: To assess potential associations between duration of glucocorticosteroid (GCS) therapy and D-dimer concentrations in children with acute urticaria. Patients, materials, and methods: Hospital records of 106 children (59 females), aged 5.57 ± 4.91 years, hospitalized in 2014–2018 were analyzed retrospectively. The study group consisted of pediatric patients admitted to the hospital due to severe acute urticaria resistant to anti-histaminic treatment that was ordered in the ambulatory care (out-patient clinic). Patients were divided into subgroups: no GCS treatment, short-duration treatment (up to 5 days) and long-duration treatment (6 and more days) GCS treatment. Simultaneously, patients received antihistaminic drugs. D-dimer level and other inflammatory factors such as white blood cell (WBC) count, platelet (PLT) count, and C-reactive protein (CRP) in each group were analyzed. Results: The D-dimer level was elevated in 51% of cases. In the subgroup with longer GCS treatment, D-dimer concentration was significantly higher in comparison to patients with a shorter GCS course. There were no differences in the distribution of CRP, PLT, and WBC concentrations between these subgroups. Conclusions: In the studied group of children, there was a tendency for higher D-dimer levels in patients, who required a longer GCS treatment. This finding is hypothesis-generating and requires further investigation to confirm if D-dimers can be used as a prognostic factor in acute urticaria in children.

Efficacy of Oral Bilastine in Comparison with Levocetirizine in Allergic Rhinitis- A Randomised Clinical Study

Introduction: Allergic rhinitis is a heterogeneous disorder characterised by major symptoms like sneezing, itching, nasal congestion and rhinorrhea. Because of bothersome side effects of first-generation antihistaminic drugs, second generation antihistaminic drugs have been used since few years. Recent studies have showed that novel drug Bilastine has been approved as an effective treatment in Allergic rhinitis. Aim: To evaluate Total Nasal Symptom Scores (TNSS), Serum Immunoglobulin E (IgE), Serum Absolute Eosinophil Count (AEC) in patients with allergic rhinitis, pre and post-treatment with Bilastine and Levocetirizine. Materials and Methods: A randomised, open-labelled, study was conducted between January 2020 to March 2020. Hundred patients with allergic rhinitis were enrolled into the study. They were randomised into two groups of which group A received tablet Bilastine 20 mg once daily for two weeks and group B received tablet Levocetirizine 5 mg once daily for two weeks. The results of TNSS, IgE, AEC and pre and post-treatment values were compared in both the treatment groups. Unpaired t-test was used as the test of significance between the two treatment groups. Results: The prevalence of allergic rhinitis in the study was 49% in males and 51% in females. The mean difference in pre and post-treatment in TNSS (group A=1.627, group B=1.143), serum IgE (A=33.118, B=49.653), serum AEC (A=28.00, B=27.245) showed no statistically significant difference between two groups (p-value >0.05). Conclusion: Bilastine and levocetirizine are equally efficacious. Though there is clinical significance in treatment of allergic rhinitis between the groups, there is no statistical significance which would prove Bilastine is clinically superior to Levocetirizine for the allergic rhinitis treatment.

LC-UV and UPLC-MS/MS Methods for Analytical Study on Degradation of Three Antihistaminic Drugs, Ketotifen, Epinastine and Emedastine: Percentage Degradation, Degradation Kinetics and Degradation Pathways at Different pH

Evaluation of pH-dependent reactivity of drugs is an essential component in the pharmaceutical industry. Thus, the stability of three antihistaminic drugs, i.e., ketotifen, epinastine and emedastine, was tested, in solutions of five pH values, i.e., 1.0, 3.0, 7.0, 10.0 and 13.0, at high temperature (70 °C). LC-UV isocratic methods were developed to estimate percentage degradation as well as the kinetics of degradation. Generally, epinastine was shown to be the most stable compound with degradation below 14%. Emedastine was labile in all pH conditions, with degradation in the range 29.26–51.88%. Ketotifen was moderately stable at pH 1–7 (degradation ≤ 14.04%). However, at pH ≥ 10, its degradation exceeded 30%. The kinetics of degradation of ketotifen, epinastine and emedastine was shown as a pseudo-first-order reaction with the rate constants in the range 10−4–10−3 min−1 Finally, the UPLC-MS/MS method was applied to identify the main degradants and suggest degradation pathways. Degradation of ketotifen proceeded with oxidation and demethylation in the piperidine ring of the molecule. As far as epinastine was concerned, opening of the imidazole ring with formation of the amide group was observed. Unfortunately, no degradation products for emedastine were detected. The present results complete the literary data and may be important for both manufacturing of these drugs and their administration to patients.