Antispasmodic Drugs Research Articles

Phytochemical analysis and investigation of analgesic, anti-inflammatory, and antispasmodic activities of hydroethanolic extracts of Alternanthera dentata, Ocimum carnosum, and Plectranthus barbatus, three species with vernacular names derived from analgesic drugs

Ethnopharmacological relevancePlant vernacular names can provide clues about the popular use of a species in different regions and are valuable sources of information about the culture or vocabulary of a population. Several medicinal plants in Brazil have received names of medicines and brand-name products. Aim of the studyThe present work aimed to evaluate the chemical composition and pharmacological activity in the central nervous system of three species known popularly by brand names of analgesic, anti-inflammatory, antispasmodic, and digestive drugs. Materials and methodsHydroethanolic extracts of Alternanthera dentata (AD), Ocimum carnosum (OC), and Plectranthus barbatus (PB) aerial parts were submitted to phytochemical analysis by HPLC-PAD-ESI-MS/MS and evaluated in animal models at doses of 500 and 1000 mg/kg. Mice were tested on hot plate, acetic acid-induced writing, formalin-induced licking, and intestinal transit tests. Aspirin and morphine were employed as standard drugs. ResultsThe three extracts did not change the mice's response on the hot plate. Hydroethanolic extracts of AD and PB reduced the number of writhes and licking time, while OC was only effective on the licking test at dose of 1000 mg/kg. In addition, AD and OC reduced intestinal transit, while PB increased gut motility. ConclusionsPharmacological tests supported some popular uses, suggesting peripheral antinociceptive and anti-inflammatory effects, while the phytochemical analysis showed the presence of several flavonoids in the three hydroethanolic extracts and steroids in PB, with some barbatusterol derivatives described for the first time in the species.

Expert opinion on current issues and challenges in irritable bowel syndrome

Irritable bowel syndrome (IBS) is a widely prevalent functional gastrointestinal disorder characterized by symptoms such as abdominal pain, irregular bowel movements, and bloating, which significantly impact affected individuals' well-being. The increasing prevalence of IBS in India places a substantial burden on clinical practice. Although diagnostic criteria, such as the commonly used Rome IV criteria, have shown reasonable sensitivity, the diagnosis of IBS remains a nuanced and culturally influenced process. This comprehensive review systematically examines current challenges surrounding IBS prevalence, diagnostic intricacies, and the complex pathophysiology involving visceral hypersensitivity. The review highlights the imperative for noninvasive biomarkers to augment diagnostic precision and emphasizes on following a holistic approach to IBS management as advocated by Indian guidelines. This approach integrates dietary modifications, antispasmodic medications, psychological therapy, and yoga, with specific emphasis on tailoring treatments to individual IBS subtypes. Among antispasmodic drugs, pinaverium bromide because of its unique mechanism of action as a calcium channel antagonist within the gastrointestinal tract has shown promise in alleviating IBS symptoms.

Phloroglucinol ameliorated methylglyoxal induced harmful effects in rats.

Glycation is among the underlying mechanisms attributed to ageing and associated morbidities. There is no drug available to combat this deleterious phenomenon. The present study aimed to explore phloroglucinol (PHL) for its anti-glycation potential at preclinical level. The rats were treated with methylglyoxal (MGO, 17.25 mg/kg, i.p. for 14 days) to induce glvcative stress. The treatment groups received additional administration of test drug (PHL; 0.25mg/kg, 0.5mg/kg, and 1mg/kg) or standard aminoguanidine (AG, 50 mg/kg) or saline (control, 5ml/kg). During 14 days, the weight and food intake was noted. Afterwards, the cognitive function was evaluated using Morris Water Maze (MWM) while hepatic and renal functions were assessed through liver function test (bilirubin, alkaline phosphatase, SGPT, and SGOT) and creatinine respectively, using chemical analyzer. The carboxymethyllysine (CML) levels were quantified in the blood using ELISA technique. Histopathological study was performed on the brain, liver, and kidney using H&E staining. Additionally, the qPCR was used to quantify the expression of TNF-α, RAGE and BACE-1 (brain), RAGE, TNF-α, and glyoxalase-I (liver) and RAGE, TNF-α, and VEGF (kidney), while glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as a reference housekeeping gene. The data regarding weight and food intake did not reveal significant alterations. In MWM, the MGO treatment caused significant increase in the time to reach target quadrant, while decrease in the time spent in target quadrant and number of crossings through platform position. All these effects were inhibited by both AG and PHL. The navigation maps also exhibit that the retention of spatial memory. Additionally, the MGO-induced alteration in hepatic and renal function indicators was ameliorated by both AG and PHL treatments. The plasma CML levels were found to be elevated following MGO treatment, while the concomitant administration of AG and PHL has resisted this raise. Histopathological assessment revealed no specific pathology in liver kidney and brain tissues. The qPCR data revealed enhanced expression of all genes, especially TNF-α and BACE, which were found to be reduced following both AG and PHL treatments. PHL prevented the brain, hepatic, and renal impairments caused by MGO induced glycative stress. Hence, the PHL, a clinically used anti-spasmodic drug, presents itself as a potential candidate to be repurposed as anti-glycation drug.

Recent Advances in the Treatment of Irritable Bowel Syndrome: Addressing Diarrhea, Constipation, and Abdominal Pain

Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder characterized by abdominal pain, bloating, and changes in bowel habits. This paper aim was to provide an overview of recent advancements in the treatment of IBS, focusing on the management of its main symptoms: diarrhea, constipation, and abdominal pain. For individuals with IBS-D, various therapeutic options are available, including rifaximin, peripheral opioid agonists, mixed opioid agonists/antagonists, bile acid sequestrants, and serotonin 5-HT3 receptor antagonists. Rifaximin, a nonabsorbable antibiotic, has demonstrated significant effectiveness in reducing IBS symptoms, such as bloating and loose stools, with good tolerability and safety. Also the repeated use of rifaximin for managing recurrent IBS symptoms. In IBS-C patients, bulking agents, osmotic laxatives, and prokinetic agents like lubiprostone have shown efficacy in improving constipation and overall symptoms. Linaclotide, a drug that increases intestinal chloride secretion, has demonstrated significant improvement in bowel movements and abdominal pain in IBS-C patients. However, it may cause diarrhea in some individuals. IBS-M, characterized by alternating constipation and diarrhea, poses a challenge in terms of specific drug treatments. A comprehensive assessment of potential underlying causes and careful history taking is crucial for effective management. Abdominal pain is a common symptom in IBS, regardless of subtype. Antispasmodic drugs, peppermint oil, and trimebutine have shown effectiveness in reducing pain and improving symptoms. Antidepressants, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may offer relief by modulating pain pathways and influencing gastrointestinal motility. Benzodiazepines, particularly dextofisopam, have shown potential in improving stool consistency but require further evaluation. In conclusion, recent advancements in the treatment of IBS have provided a range of therapeutic options targeting its main symptoms. However, further research is needed to develop tailored treatments for specific IBS subtypes and to explore the efficacy of potential alternatives, including benzodiazepines. Improved management of IBS symptoms can significantly enhance the quality of life for affected individuals.

Papaverine prior to catheter balloon insertion for labor induction: a randomized controlled trial

Catheter balloon insertion is a common method for cervical ripening and labor induction. Papaverine and its derivatives are musculotropic antispasmodic drugs that directly induce smooth muscle relaxation. Used during childbirth, these drugs have been suggested to shorten the duration of labor. This study aimed to evaluate the effect of administering papaverine before catheter balloon insertion on changes in Bishop scores and on the labor induction-to-delivery interval. This randomized, double-blinded, placebo-controlled trial was conducted in a single tertiary university-affiliated hospital. Participants were admitted at term for labor induction with an initial Bishop score of ≤6. Participants were randomized to receive 80 mg intravenous papaverine or 0.9% normal saline solution within 30 minutes of Foley catheter balloon insertion. The co-primary outcomes were the difference in Bishop score from before catheter balloon insertion to after removal and the labor induction-to-delivery interval. The secondary outcomes included maternal pain and satisfaction scores, delivery within 24 hours, and neonatal outcomes. Both intention-to-treat and per-protocol analyses were performed. Overall, 110 women were enrolled. In the intention-to-treat analysis, the median difference in Bishop score was greater in the papaverine group than in the placebo group (5 [interquartile range, 1-11] vs 4 [interquartile range, 0-7], respectively; P=.025), and the median catheter balloon insertion-to-delivery interval was shorter in the papaverine group than in the placebo group (21 hours [interquartile range, 6-95] vs 26 hours [interquartile range, 3-108], respectively; P=.031). A higher proportion of women delivered within 24-hours in the papaverine group than in the placebo group (65.5% vs 41.8%, respectively; P=.012). Pain and satisfaction scores, delivery, and neonatal outcomes were similar between the groups. Similar results were found in the per-protocol analysis. Papaverine administration before Foley catheter balloon insertion for cervical ripening resulted in improved Bishop scores and shorter catheter balloon insertion-to-delivery intervals.

Effect of alverine citrate plus simethicone in colonoscopy: a randomized controlled trial.

Colonoscopy is the standard procedure for screening, and surveillance of colorectal cancer, including the treatment for colonic lesions. Colonic spasm is an important problem from colonoscopy that affects both surgeons and patients. The spasm also might be the cause of longer cecal intubation time, difficulty of the procedure, and increased pain. Previous reports indicated that antispasmodic agents can decrease such symptoms. Therefore, we conducted this study to investigate the cecal intubation time of antispasmodic agents. A single blinded randomized controlled trial was conducted from 01/11/2020 to 31/08/2021. One hundred four patients were allocated to antispasmodic agent group and control group, in 1:1 ratio. The efficacy of median (range) cecal intubation time showed similar results of 5 (2, 14) and 5 (2, 15) minutes with no statistically significant difference. The mean scores of all domains i.e., pain, spasm, cleanliness, and difficulty were better in the antispasmodic agent group about 2.6 (1.4), 1.8 (0.8), 2.4 (0.9), and 2.0 (0.9), respectively, than control group but there were spasm and cleanliness showed statistically significant difference. Moreover, the satisfaction scores showed better efficacy in decreased spasm, decreased difficulty, and increased cleanliness than control group. Prescribing of antispasmodic drugs before colonoscopy might be the choice of treatment for the patients. The antispasmodic drugs will be beneficial to both of the patient and the doctor.

Characterization of Chemical Interactions between Clinical Drugs and the Oral Bacterium, Corynebacterium matruchotii, via Bioactivity-HiTES.

In the field of natural product research, the rediscovery of already-known compounds is one of the significant issues hindering new drug development. Recently, an innovative approach called bioactivity-HiTES has been developed to overcome this limitation, and several new bioactive metabolites have been successfully characterized by this method. In this study, we applied bioactivity-HiTES to Corynebacterium matruchotii, the human oral bacterium, with 3120 clinical drugs as potential elicitors. As a result, we identified two cryptic metabolites, methylindole-3-acetate (MIAA) and indole-3-acetic acid (IAA), elicited by imidafenacin, a urinary antispasmodic drug approved by the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). MIAA showed weak antibacterial activity against a pulmonary disease-causing Mycobacterium conceptionense with an IC50 value of 185.7 μM. Unexpectedly, we also found that C. matruchotii metabolized fludarabine phosphate, a USFDA-approved anticancer drug, to 2-fluoroadenine which displayed moderate antibacterial activity against both Bacillus subtilis and Escherichia coli, with IC50 values of 8.9 and 20.1 μM, respectively. Finally, acelarin, a prodrug of the anticancer drug gemcitabine, was found to exhibit unreported antibacterial activity against B. subtilis with an IC50 value of 33.6 μM through the bioactivity-HiTES method as well. These results indicate that bioactivity-HiTES can also be applied to discover biotransformed products in addition to finding cryptic metabolites in microbes.

Phloroglucinol inhibited glycation via entrapping carbonyl intermediates.

Advanced glycation end products (AGEs) play an important role in the pathogenesis of age-linked disorders and diabetes mellitus. The aim of this study was to assess the repurposing potential of Phloroglucinol (PHL the antispasmodic drug), as an anti-glycation agent using Fructose-BSA model. The ability of PHL to inhibit AGE formation was evaluated using AGEs formation (Intrinsic fluorescence), fructosamine adduct (NBT) and free lysine availability (TNBSA) assays. The BSA protein conformation was assessed through Thioflavin-T, Congo-Red and Circular Dichroism assays. The lysine blockade and carbonyl entrapment were explored as possible mode of action. Our data showed that PHL significantly decreased the formation of AGEs with an IC50 value of 0.3mM. The fructosamine adducts and free lysine load was found to be reduced. Additionally, the BSA conformation was preserved by PHL. Mechanistic assays did not reveal involvement of lysine blockade as underlying reason for reduction in AGEs load. This was also supported by computational data whereby PHL failed to engage any catalytic residue involved in early fructose-BSA interaction. However, it was found to entrap the carbonyl moieties. In conclusion, the PHL demonstrated anti-glycation potential, which can be attributed to its ability to entrap carbonyl intermediates. Hence, the clinically available antispasmodic drug, presents itself as a promising candidate to be repurposed as anti-glycation agent.

Age and treatment on the day of embryo transfer in recipient mares affect likelihood of pregnancy.

This retrospective evaluation of data from a large commercial embryo transfer facility aimed to determine the extent to which age and treatment on the day of embryo transfer in recipient mares influence the likelihood of pregnancy. Embryo recovery was carried out on days 8-10 post-ovulation using transcervical uterine flushing. Recipient mares grouped according to their age were treated once on the day of embryo transfer (Day 3-8 post ovulation) and were assigned randomly to 1 of 3 groups: Mares in Group A (n=101) received antispasmodic, antimicrobial, and anti-inflammatory drugs. Mares in Group B (n=100) received gentamicin and flunixin meglumine. Group C (control) (n=103) did not receive any treatment. Detomidine (0.008 mg/kg bwt i.v.) was administered to all recipients before transfer of the embryo. The influence of treatment and recipient´s age was calculated using binary logistic regression. Day 16 post-transfer pregnancy rates were highest in Group A (74/101, 73.3a%), when compared to Group B (60/100, 60%), and Group C (57/103, 55.3b%) (a vs b, p<0.05). Pregnancy loss rates at D45 were not different between groups, A (8/74, 10.8%), B (5/60, 8.3%), and C (6/57, 10.5%), respectively (p>0.05). Pregnancy losses were increased in recipient mares 17-22 years (33.3a%) compared to younger recipient mares (2-6 years 7b%, 7-11 years 10%, 12-16 years 8b%) (a:b p<0.05). The regression model showed that the predicted probability for pregnancy after embryo transfer decreased as the age of the recipient mare increased for treated recipients in Group A (p=0.012), there was no effect of treatment and recipient´s age in Group B, and a decreased likelihood of pregnancy in recipients of advanced age (≥12 years of age) in untreated recipients (group C). Likelihood of pregnancy increased following single administration of antispasmodic, antimicrobial, and anti-inflammatory drugs at the time of embryo transfer in recipients 2-12 years of age. Likelihood of pregnancy in recipients decreased in recipients≥12 years of age. These results, obtained under the conditions of a large commercial embryo transfer program, offer an opportunity to improve pregnancy rates in recipient mares≤12 years of age.

Pharmacological Management for Pediatric Irritable Bowel Syndrome: A Review.

Irritable bowel syndrome is a multifactorial disease with chronic symptoms that interfere with the quality of life of patients. It represents one of the most common causes of functional abdominal pain in the pediatric population. Various theses with little evidence tried to explain the pathophysiology of the disease. Neurological origin was one of the theories explaining the disease, either by the disturbance of neurotransmitters like dopamine, noradrenaline, and serotonin, which have some evidence of their relation to GI tract functions. Other factors like bio-psycho-social factors that affect the pediatric population are represented in bullying, unrealistic academic expectations from the parents, continuous educational stress, and difficult relationships with peers. Other factors may be genetic abnormalities of the receptors or visceral hypersensitivity. Treatment strategies for the disease varied from physical activity like yoga to a diet like a low-FODMAP diet. Pharmacological treatment of the disease targets the presenting symptoms, represented by antispasmodic drugs treating abdominal pain/discomfort, antipsychotics that regulate the disturbance in the brain-gut axis, and other drugs targeting diarrhea or constipation that present with the patient according to the type of IBS and the condition of the patient.

Structural basis for human Cav1.2 inhibition by multiple drugs and the neurotoxin calciseptine

Cav1.2 channels play crucial roles in various neuronal and physiological processes. Here, we present cryo-EM structures of human Cav1.2, both in its apo form and in complex with several drugs, as well as the peptide neurotoxin calciseptine. Most structures, apo or bound to calciseptine, amlodipine, or a combination of amiodarone and sofosbuvir, exhibit a consistent inactivated conformation with a sealed gate, three up voltage-sensing domains (VSDs), and a down VSDII. Calciseptine sits on the shoulder of the pore domain, away from the permeation path. In contrast, when pinaverium bromide, an antispasmodic drug, is inserted into a cavity reminiscent of the IFM-binding site in Nav channels, a series of structural changes occur, including upward movement of VSDII coupled with dilation of the selectivity filter and its surrounding segments in repeat III. Meanwhile, S4-5III merges with S5III to become a single helix, resulting in a widened but still non-conductive intracellular gate.

Antispasmodic Effect of Alstonia boonei De Wild. and Its Constituents: Ex Vivo and In Silico Approaches.

Alstonia boonei, belonging to the family Apocynaceae, is one of the best-known medicinal plants in Africa and Asia. Stem back preparations are traditionally used as muscle relaxants. This study investigated the antispasmodic properties of Alstonia boonei Stem back and its constituents. The freeze-dried aqueous Stem back extract of A. boonei, as well as dichloromethane (DCM), ethyl acetate, and aqueous fractions, were evaluated for their antispasmodic effect via the ex vivo method. Two compounds were isolated from the DCM fraction using chromatographic techniques, and their antispasmodic activity was evaluated. An in silico study was conducted by evaluating the interaction of isolated compounds with human PPARgamma-LBD and human carbonic anhydrase isozyme. The Stem back crude extract, DCM, ethyl acetate, and aqueous fractions showed antispasmodic activity on high-potassium-induced (K+ 80 mM) contractions on isolated rat ileum with IC50 values of 0.03 ± 0.20, 0.02 ± 0.05, 0.03 ± 0.14, and 0.90 ± 0.06 mg/mL, respectively. The isolated compounds from the DCM fraction were β-amyrin and boonein, with only boonein exhibiting antispasmodic activity on both high-potassium-induced (IC50 = 0.09 ± 0.01 µg/mL) and spontaneous (0.29 ± 0.05 µg/mL) contractions. However, β-amyrin had a stronger interaction with the two proteins during the simulation. The isolated compounds boonein and β-amyrin could serve as starting materials for the development of antispasmodic drugs.

QbD: A novel approach for formulation and optimization of colon targeted drug delivery system containing mebeverine HCl

The aim of the work is to study the programmed release of model antispasmodic drug Mebeverine HCl based on pulsatile principle to target colon proximity. Compression coated tablets included core tablet consisting of Croscarmellose as super disintegrant and pulsatile layer comprising impermeable Ethocel cup and mixture of Keltone, Eudragit S100, Ethocel as swellable and rupturable layer. The prepared core tablet was evaluated for weight variation, hardness, thickness, friability, drug content, disintegration time and in vitro dissolution studies. For optimization Box-Behnken design was employed to study the effect of independent variables viz., weight ratio of Keltone (X1), Eudragit S100 (X2), Ethocel (X3) on dependent variables viz., t10 (Y1), t50 (Y2) and Q12 (Y3). Results revealed positive influence of independent factors on responses. The data were statistically analyzed using ANOVA and were found to be statistically significant (P &lt; 0.05). Mathematical modeling for kinetic studies revealed that the release profile after lag time followed first order kinetics. The results concluding that a successful pulsatile drug delivery system of Mebeverine HCl was developed.

Reformation of Reproductive Health Using Havishyaanna in Rajaswalacharya

It’s been years that women are suffering from general disturbances associated with menstruation like abdominal pain, psychological stress, disturbed bowel movements. PG inhibitors and antispasmodic drugs etc are the popular mode of medication used in regular gynaecological clinical practice. It can give relief to the patient but has limitations over preventing the recurrence, which is, tend to happen mainly in adolescent and middle aged women due to modern lifestyle. According to Ayurveda, menstruation is a physiological process and governed by the actions of the three balanced state Doshas exist in a proper and its inequality causes abnormal menstruation. There are amazing diets and lifestyle modification given in Ayurveda which are beneficial to restore menstrual health with different combinations given in the ancient texts. Amongst all given possible diets during menstruation, Havishyanna - special diet is the most feasible as patients can make it on its own, consume for first three days of menstrual cycle which requires very less timing and has simple procedure. Menstruating women can deal with symptomatic and psychological changes occur during the menstruation by practicing Rajaswala Paricharya. Addition to this Havishyanna helps to reform reproductive health, it maintains balance of Vata dosha during menstruation, proper Rajavahan and Rajasrav, proper Rutukal nirmiti which helps to form high quality of oocyte, maintain healthy uterine environment, all these able to carry healthy pregnancy, in turn healthy Progeny.

Current clinical application of dantrolene sodium.

Dantrolene sodium (DS) was first introduced as an oral antispasmodic drug. However, in 1975, DS was demonstrated to be effective for managing malignant hyperthermia (MH) and was adopted as the primary therapeutic drug after intravenous administration. However, it is difficult to administer DS intravenously to manage MH. MH is life-threatening, pharmacogenomically related, and induced by depolarizing neuromuscular blocking agents or inhalational anesthetics. All anesthesiologists should know the pharmacology of DS. DS suppresses Ca2+ release from ryanodine receptors (RyRs). RyRs are expressed in various tissues, although their distribution differs among subtypes. The anatomical and physiological functions of RyRs have also been demonstrated as effective therapeutic drugs for cardiac arrhythmias, Alzheimer's disease, and other RyR-related diseases. Recently, a new formulation was introduced that enhanced the hydrophilicity of the lipophilic DS. The authors summarize the pharmacological properties of DS and comment on its indications, contraindications, adverse effects, and interactions with other drugs by reviewing reference articles.

Study of analgesic and myotropic spasmolytic activity of alkylcarb

The work is devoted to the search for new biologically active substances in a series of alkylamides of dihydroquinoline-3-carboxylic acid. Analgesic properties of 30 newly synthesized substances were studied, which made it possible to identify the leader compound (provisional name alkylcarb) and recommend its effectiveness for further research as an antispasmodic agent for pain relief. It has been established experimentally, that the substance alkylcarb exhibits concentration-dependent vasodilatory properties in vitro on segments of the thoracic aorta of rats. The data, obtained in the work, justify the prospect of using the leader substance as a new analgesic and antispasmodic drug. The research expands and deepens knowledge about the pharmacological properties of alkylamide derivatives of dihydroquinoline-3-carboxylic acid.&#x0D; The aim of the work was to conduct screening studies to establish the analgesic activity of a newly synthesized series of chemical compounds among alkylamides of dihydroquinoline-3-carboxylic acid and to study the myotropic spasmolytic activity of the leader substance.&#x0D; Materials and methods. Analgesic properties of alkylamides of dihydroquinoline-3-carboxylic acid were studied on outbred white mice in the "acetic acid convulsions" test. During the experiment, the animals were treated in accordance with the International Principles of the European Convention for the Protection of Vertebrate Animals Used for Experiments and Other Scientific Purposes (Strasbourg, March 18, 1986). The studied substances were administered intragastrically to experimental animals at a dose of 10 mg/kg in the form of a finely dispersed aqueous suspension, stabilized with Tween-80. Voltaren at a dose of 8 mg/kg, recommended for preclinical studies, and analgin at a dose of 50 mg/kg were chosen as reference drugs.&#x0D; The studies of the contractile activity of smooth muscle vessels were carried out on segments of the thoracic aorta of rats of both sexes weighing 180-200 g. The studies of dilator reactions were carried out against the background of preliminary contraction with phenylephrine at a concentration of 10-6 mol/l. The antispasmodic efficiency of the new compound was determined in comparison with the classic antispasmodic drotaverine.&#x0D; The statistical processing of the results was carried out using the package of statistical analysis of electronic spreadsheets Exel, with the help of the program "Statgraphics Plus v. 3.0.” and the standard package of statistical programs "Statistica, V. 6.0". We used the Student's test, a non-parametric analog of univariate variance analysis - the Kruskal-Wallis test, and the Mann-Whitney test. Differences were considered statistically significant at p&lt;0.05.&#x0D; Results. The study of the analgesic activity of substances АO1-АO30 in the "acetic acid convulsion" test in mice showed that a compound АO26 (provisional name alkylcarb) has the most pronounced analgesic activity when administered intragastrically. In the "acetic acid convulsion" test, alkylcarb (10 mg/kg, per os) probably reduces the number of convulsions, caused by acetic acid. The level of activity of this compound is comparable to the activity of diclofenac (8 mg/kg, per os) and exceeds analgin (50 mg/kg, per os). The substance alkylcarb relieved vasospasm at the level of the comparison drug drotaverine in in vitro experiments on a model of an isolated fragment of the thoracic aorta of rats against the background of previous constriction with phenylephrine.&#x0D; Conclusion. Today, the search for new highly effective non-opioid analgesics is an urgent problem of modern pharmacology, since painkillers used in clinical practice do not meet the requirements of efficiency and safety. In this regard, in recent years, scientists of the National Pharmaceutical University have been intensively searching for new, highly effective substances with antinociceptive, anti-inflammatory and antipyretic effects among alkylamides of dihydroquinoline-3-carboxylic acid.

Pharmacognostic Study of Ehretia acuminata R.Br.

Ehretia acuminata, commonly known as “Puna” in Pakistan, is from the Boraginaceae family and is used in ecological, medicinal, and agricultural sectors. The current study was conducted to assess the pharmacognostic potency of bark extracts from E. acuminata. The crude distilled water, ethanol, and chloroform extracts signified a concentration-dependent increase in intestinal mobility of the experimented animal, and the plant delivered methodical proof for its pharmacological usage as an antispasmodic drug. The bark distilled water, bark ethanol, and bark chloroform extracts revealed (11±1, 9±1, and 11±1) antispasmodic potential at (300 mg/kg). The distilled water, ethanol, and chloroform extracts also showed analgesic potential in the present study and the results were concentration dependent. The bark distilled water, bark ethanol, and bark chloroform extracts revealed the (10±1,16±1, and 11±1) analgesic potential at (300 mg/kg). The distilled water, ethanol, and chloroform extracts also showed the muscle relaxant potential in this study and the results were concentration dependent. The Bark distilled water, Bark ethanol, and Bark chloroform extracts revealed the (6±1, 5±1, and 5±1) at (300 mg/kg). While the distilled water, ethanol and chloroform extracts did not show acute toxic effects against the tested animal mice. In this study, bark extracts of E. acuminata showed pharmacological potency in experimental animals. The plant delivered scientific proof for its pharmacological usage as an antispasmodic, acutely toxic, muscle relaxant, as well as an analgesic drug.

The place of antispasmodic drugs in modern therapy of irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common functional disease of the gastrointestinal tract, affecting a large number of adults worldwide, and leads to a significant decrease in the quality of life. IBS places a heavy burden on patients, most of whom are able-bodied population, as well as doctors and the healthcare system. The pathogenesis of this disease is multifactorial and includes the brain-intestine axis, disorders of the immune function of the mucous membrane, visceral hypersensitivity, changes in the motility of the gastrointestinal tract, changes in the microbial composition of the intestine. Based on the fact that changes in intestinal motility and visceral hypersensitivity are among the key factors in the pathogenesis of the disease, he use of antispasmodic drugs as part of complex therapy is justified. Mebeverin is a myotropic antispasmodic drug recommended for use in patients with IBS according to Rome IV Criteria, as well as clinical recommendations of the Russian Gastroenterological Association and the Association of Coloproctologists of Russia. According to available data, mebeverin has proven to be an effective and safe antispasmodic used to treat patients with IBS. The article presents a clinical case demonstrating the experience of effective use of the drug Mebespalin®. A patient with a diagnosis of IBS with a predominance of constipation is recommended to take an antispasmodic, as well as lifestyle modification – the addition of fiber-rich foods, sufficient drinking regime and increased physical activity. A week after the start of treatment, the patient noted an improvement in her condition – abdominal pain did not bother, the stool normalized.

ELABORATION OF CHEMICAL SENSOR SENSITIVE TO BORON BENZILATE

Over the last decades, the development of simple and selective methods for the determination of organic analytes has been getting attention from analytical chemists. Particularly, the same applies to biologically active substances of natural and artificial origin, precursors, and metabolites of pharmaceuticals[1]. An example of such substance is benzylic acid (2, 2-diphenyl-2-hydroxyacetic acid) (BA), gravimetric reagent for zirconium [2], a product of hydrolysis and a metabolite of the antispasmodic and sedative drugs Pipoxolan, Benactyzine, or Metacin [3]. The complexes of BA have been proposed as corrosion inhibitors for some steels and aluminum alloys [4]. Its derivatives are being studied as new analgesics [5], anticancer drugs [6], and also as deep eutectic solvents [7]. The BA was used in the synthesis of the psychotropic combatant substance 3-quinuclidinyl benzilate (BZ), which causes mental slowing, and hydrolyzes to form BC [8-11]. For BA determination high-performance liquid chromatography and chromatography-mass spectrometry [12-15] are mostly used, hence the development of simple methods for determining benzylic acid is pertinent and relevant.&#x0D; Boric acid is known to form compounds with diols, α-hydroxy acids, dicarboxylic acids, and α-diketones [16] and that was used in developing potentiometric sensors for the determination of mandelic acid and vitamin C [17, 18]. As BA also forms complexes with boric acid and various metals [19, 20] the H3BO3 has been used in the present study as a reagent for obtaining boric acid benzilate ester - the analytical form of BA, as well as the ionic associate of its anion with tetraoctylammonium(TOA) as the active substance of a potentiometric PVC plasticized sensor sensitive to the mentioned above analytical form. The complex formation has been confirmed using IR spectroscopy. On the IR spectrum of BA, the absorption bands in the region of 3393. 69 cm-1 and 1715. 77 cm-1, which correspond to the vibrations of –ОН and &gt;С=О groups, respectively have been detected [23]. At the same time, in the IR spectrum of the complex, the absorption band of –ОН groups in the region of 3300 - 3400 cm-1 was absent, that indicates their participation in the formation of ether bonds, additionally, the intensive bands of &gt;C=O in the region of 1723. 41 cm-1 and 1742. 05 cm-1 has appeared. The ion pair of tetraoctylammonium cation with synthesized complex ion [B(Benz)2]- has been used as an active substance of the potentiometric sensor. The metrological and operational characteristics of the sensor and the optimal conditions of the analytical form obtaining have been systematically studied. The optimized composition of the sensitive PVC membrane was 0. 1% of IP, 33. 0% of PVC and 66. 9% of o-NFOE. For high yield [B(Benz)(ОН)2]--analytical form preparation the boiling of BA for 15 minutes in the medium of a buffer solution that consists of H3BO3 (sat.) - 0. 1 M NaOH - 0. 1 M H3PO4 with a pH of 5. 5 is needed. In optimal conditions, the slope of the sensor developed is close to the theoretical value of 55. 2 mV/pС, has a detection limit pCmin= 4. 9, and the linearity range 10-2 – 10-4mol/l. The response time of a sensor ranges from 5 to 30 seconds depending on the added quantity. High selectivity of the sensor to metal cations, anions of organic and inorganic acids, as well as polyatomic alcohols that are able to form complex compounds with BA or H3BO3 has been shown. The sensor developed was used for benzylic acid analysis in "Difenin", which can be formed during the synthesis of this drug [27].&#x0D; It has been shown that the use of potentiometry in combination with the conversion of the analyte into an active form using a cheap reagent - boric acid allows to develop simple methods of the organic analytes determination for which the use of potentiometry is not common. Preparation of the complex boronate ester of benzylic acid in the sample provides the selectivity of the technique to the target analyte.&#x0D; Keywords: benzylic acid; boron benzilate; potentiometric sensor; ion pair.

A Theoretical Approach on the Action of Vilwadi Agada in Relieving the Symptoms of Acute Gastroenteritis

Ayurveda a unique science of life, which emphasized on the principle of protecting the health of a healthy individual and eradicating the disease in diseased persons. Now a days, people living in the midst of diseases that disturb them to achieve a good health. The people are trying to overcome this situation by developing an art of medicine and science of healing. Agadatantra is one of the branches in Ayurveda. Literally’ Agada’ means a disease-free condition. It deals with different type of poisoning from animate and inanimate objects with its management. The poisoning from the bite of snakes, spiders, insects, rodents and from the combination of different poisons with their management are included in this branch. Vilwadi agada is a polyherbal combination can be used in various toxicological conditions, GIT problems, concocted poisoning, systemic symptoms like fever, infectious conditions. Today Vilwady agada is marketing as Vilwady gutika by different pharmaceutical companies. Classical reference of Vilwadi agada mentioned in Ashtangahridaya, Ashtangasamgraha, Sahasrayogam, Visha Jyotsnika and Kriyakoumudhi. Acute gastroenteritis (stomach flu) is an infection characterised by diarrhoea, cramps, nausea, vomiting and fever with inflammation of gastric mucosa. Viruses are the important causative factors for 70% of the episodes of acute gastroenteritis in children especially the rota virus. In contemporary science the first choice is oral rehydration therapy and then gives anti diarrhoeal drugs, antiemetics, antispasmodic drugs according to the condition of the patient. The drugs in Vilwadi agada having antimicrobial, antiviral, analgesic, anti- inflammatory, antioxidant, carminative properties. These attributes of this combination is very effective in relieving the cardinal symptoms such as abdominal cramps, nausea, vomiting diarrhoea and fever in acute gastroenteritis.