A Review on Acotiamide

Functional dyspepsia (FD) is mainly treated by drugs like H2 receptors antagonists, Proton pump inhibitors, prokinetics. A novel prokinetic drug to treat FD with 2 subtypes: Epigastric pain syndrome (EPS) & postprandial distress syndrome (PDS), has been introduced recently by the approval of Acotiamide, the first in class, muscarinic receptor antagonist & cholinesterase inhibitor. It has shown improvement in gastric motility in rodents & dogs and reduced PDS symptoms in patients in Double- blinded multicentric study.

SKRINING SENYAWA INHIBITOR H2 DARI KAYU MANIS (Cinnamomum verum J.Presl)

Digestive tract disorders, especially gastric disorders, are often experienced by people. One drug to treat this disorder has a mechanism of blocking the H2 receptor. This research was conducted to find compounds from C.verum which have the stability of bind to H2 receptors. The method used is protein modeling with swiss-model, docking with PLANTS (CHEMPLP) and activity prediction. The test results obtained that the docking score was ?- amorphene (-65,79), ?-bergamotene (-65,48), ?-copaene (-66,62), ?-cubebene (-66,46), Cadinene (-64 , 79), Camphor (-52.15), Caryophyllene (-62.61), Cinnamaldehyde (-68.17), Epicatechin (-80.43), Ergosterol (-85.24), Eugenol (-67.35), Hydrocinnamaldehyde (-65,53), Quercetin (-74,38), Protocatechuic acid (-71,49), Stigmasterol (-88,88), 4- (2,3-dihydro-3- (hydroxymethyl) - 5- (3-hydroxypropyl) -7- (methoxy) benzofuranyl] -2-methoxyphenyl (-85,29). Combined with the probability activity of compounds that have the potential to be further developed are Epicatechin and urolignoside.

Relaxant Effects of the Aqueous Extract of Excoecaria grahamii (Euphorbiaceae) Leaves on Uterine Horn Contractility in Wistar Rats

In uterine smooth muscle, the effects of Excoecaria grahamii are not yet documented. To fill this gap, we investigated the pharmacological effect of Excoecaria grahamii on the contraction of the rat isolated uterine horns. The isolated segments were exposed to different concentrations of the aqueous extract of Excoecaria grahamii leaves and pharmacological drugs. The results showed that Excoecaria grahamii aqueous extract decreased the amplitude and frequency by concentration-related manner. I C 50 values were 2.4 and 2.6, respectively, for amplitude and frequency. Our study revealed that the extract did not act through histamine H2-receptors or the nitric oxide pathway. It also inhibited uterine contractions induced by oxytocin and potassium chloride (KCl). These data suggest that Excoecaria grahamii active compound can be used for calming uterine contractions. The action of Excoecaria grahamii showed that it can be useful to fight against diseases which caused uterotonic effects. It can be useful to prevent preterm birth and pains caused by menstruations but further investigation is needed to clarify the mechanism action.

Famotidine Repurposing for Novel Corona Virus Disease of 2019: A Systematic Review

Background COVID-19 caused by SARS-CoV-2 was declared as a global pandemic by the WHO. Famotidine is a histamine-2 (H2) receptor antagonist which blocks the H2 receptors in the parietal cells, decreasing gastric acid secretion. Our review aims to study all the available scientific evidence on famotidine research outcomes systematically to introspect its clinical efficacy and probable mechanisms and clinical efficacy against SARS-CoV-2. Methodology An electronic search of PubMed, Scopus and Google Scholar was performed using MeSH terms “SARS CoV-2” OR “COVID-19” AND“FAMOTIDINE”. Relevant informationwas extracted from studies reporting the efficacy of famotidine in COVID-19. Results We found a total of 32 studies, out of which only 14 were relevant and were included in our review.Molecular computational studies showed that famotidine selectively acts on viral replication proteases papain-like protease (PLpro) and 3-chymotrypsin-like protease (3CLpro). Additionally, it acts via inverse-agonism on the H2 receptors present in neutrophils and eosinophils which leads to inhibition of cytokine release. Clinical study findings have pointed toward significant improvements in COVID-19 patient-reported symptoms in non-hospitalized patients and reduction in intubation or death in critically ill patients associated with the usage of famotidine. However,in one of the studies,famotidine has failed to show any significant benefit in reducing mortality due to COVID-19. Conclusion Famotidine has the potential to answer the ongoing global challenge owing to its selective action on viral replication. Additionally, clinical findings in COVID-19 patients support its efficacy to reduce clinical symptoms of COVID-19.We suggest that further optimally powered randomized clinical trials should be carried out to come up with definitive conclusions.

Intra-arterial injection of bradykinin produces reflex cardiorespiratory changes involving histamine receptors in anesthetized rats

Objectives: It is well known that intra-arterial injection of nociceptive agent produces vasosensory reflex responses altering cardiorespiratory parameters. The role of various inflammatory mediators is also implicated in the regulation of these reflex responses. However, the role of histamine in this regard is not clear. This study was performed to understand the role of H1 and H2 receptors in modulating the cardiorespiratory responses evoked after i.a. injection of bradykinin (BK). Materials and Methods: Male albino rats were anesthetized with an intra-peritoneal injection of urethane (1.5 g/kg). Tracheostomy was performed to keep the respiratory tract patent. The femoral artery was cannulated proximally by pediatric i.v. cannula (24 G, double ported). This cannulation was used for the blood pressure (BP) recording as well as for the drugs instillation as it contains double port with injection valve. The effect of BK (1 µM) on BP, electrocardiographic, and respiration was recorded for 30 min. The respiratory frequency, respiratory minute volume, mean arterial pressure, and heart rate were computed from the original tracings and the data were presented as mean ± SEM. Results: Intra-arterial injection of BK produced immediate hyperventilatory (50% from initial), hypotensive (40% from initial), and bradycardiac responses (17% from initial) of shorter latency (5–8 s) indicating the neural mechanisms in producing the responses. Pre-treatment with pheniramine maleate significantly attenuated the BK-induced hyperventilatory (11% from initial), hypotensive (8% from initial), and bradycardiac responses (2% from initial). Conclusion: Our data provide evidences for the involvement of H1 and H2 receptors in producing the BK-induced vasosensory reflex responses modulating the cardiovascular parameters in anesthetized rats.

A Comparative Study of Efficacy of Alcaftadine 0.25 % and Olopatadine 0.2 % in Allergic Conjunctivitis

BACKGROUND Allergic conjunctivitis is one of the commonly found clinical conditions in ophthalmology practice. Diagnostic features consist of itching, redness and swelling of conjunctiva. Cornea is rarely involved. The physiologic basis of allergy is mast cell degranulation releasing histamine and other pro-inflammatory mediators. Mast cells release histamine which is responsible for early acute phase of allergies and pro-inflammatory mediators like prostaglandins, leukotrienes etc. which are responsible for the late phase. Activation of H1 receptors on conjunctival neurons causes itching while that of H1 and H2 receptors on vascular endothelium is responsible for vasodilation (appearing as redness) and endothelial swelling. Itching and inflammation are caused by response of H4 receptors on immune and inflammatory cells. Olopatadine is an H1 receptor antagonist and mast cell mediator release inhibitor. It is available as 0.1 % formulation used twice daily, and 0.2 % and 0.7 % formulations, both used once daily. Alcaftadine has high affinity and specificity for H1 and H2 receptors, and moderate affinity for the H4 receptors. It is an inverse agonist of H1, H2 and H4 receptors and also acts as mast cell stabiliser. Thus, antihistaminic effect relieves the early phase and mast cell stabilisation relieves the late phase of ocular allergic response. Both have become the most important therapy for allergic conjunctivitis. METHODS This was a prospective, observer-masked, single centre clinical trial conducted at outpatient department of ophthalmology, S.N. Medical College, Agra, from February 2018 to July 2019. Subjects with allergic conjunctivitis (n = 136) were registered for a prospective study and followed up for two weeks. Subjects were randomised using computer generated random number tables into one of the two treatment groups: alcaftadine 0.25 % eye drop and olopatadine 0.2 % eye drop. In this study, efficacy of the drug was taken as mean reduction in severity score of the subjects evaluated at one week and two weeks follow up. RESULTS Patients treated with alcaftadine 0.25 % eye drop showed comparatively early alleviation of signs and symptoms in comparison to patients treated with olopatadine 0.2 % eye drop. Alcaftadine 0.25 % treated subjects experienced significantly higher mean reduction in severity score than olopatadine 0.2 % treated subjects at every follow up visit; after 1 week (p = 0.0205) and after 2 weeks (p = 0.0475). No adverse effects were reported with either drug. CONCLUSIONS Once daily alcaftadine 0.25 % eye drop showed higher efficacy than once daily olopatadine 0.2 % eye drop in relieving signs and symptoms of allergic conjunctivitis at both one week and two weeks follow up. Both treatment arms were found to be safe and effective. KEYWORDS Allergic conjunctivitis, Olopatadine, Alcaftadine

Histamine

Histamine has at least twenty-three known physiological functions, including playing a prominent role in immunologically mediated inflammation. The structure and metabolism of histamine is discussed, together with the various types of histamine receptors. Histamine plays a role in anaphylaxis, mast cell activation syndromes and mastocytosis and these conditions are relevant to anaesthetic practice. The antihistamine drugs and the H2 receptors agonists are discussed with regard to their role in anaesthesia.

An Herbal H2 Blocker in Melasma Treatment

Background: Melasma is a skin pigmentation disorder that remains resistant to available therapies. The exact cause of melasma is unknown. Histamine is an inflammatory factor. Its involvement in pigmentation is obscure. The aim of this study is to introduce an herbal antihistamine H2 receptor which is effective in these disorders. Methods: This is a review study by searching the electronic databases and also Persian Medicine books, from 2000 to 2018 by the keywords such as H2 antagonist, H2 blocker and melasma. Results: According to the researched studies, histamine can induce melanogenesis and melasma after a series of stages in the body. Also, Histamine, through receptors 2, triggers melasma. Therefore, it can be said that antihistamine H2 receptor can be effective in melasma. Considering chemical antihistamine, H2 receptors have side effects, such as digestive problems, H2 antagonists can be used in the treatment of diseases such as dyspepsia but they have multiple complications. On the other hand, there is an herbal H2 antagonist that can be useful for melasma due to having some special properties. Conclusion: Herbal H2 blockers should be noted in melasma treatment along with the topical drugs.