Spasmolytic Effect Research Articles

The history, current state and perspectives of aerosol therapy.

Nebulization is a very effective method of drug administration. This technique has been popular since ancient times when inhalation of plants rich in tropane alkaloids with spasmolytic and analgesic effects was widely used. Undoubtedly, the invention of anasthesia in the 19th century had an influence on the development of this technique. It resulted in the search for devices that facilitated anasthesia such as pulveriser or hydronium. From the second half of the 21st century, when the first DPI and MDI inhalers were launched, the constant development of aerosol therapy has been noticed. This is due to the fact that nebulization, compared with other means of medicinal substance application (such as oral and intravenous routes of administration), is safer and it exhibits a positive dose/efficacy ratio connected to the reduction of the dose. It enables drugs administration through the lung and possesses very fast onset action. Therefore, various drugs prescribed in respiratory diseases (such as corticosteroids, β-agonists, anticholinergics) are present on the market in a form of an aerosol.

Antidiarrheal and Antioxidant Activities of the Aerial Parts of Caralluma dalzielii N. E. Brown

Pharmacognosy Research,2022,14,1,82-88.DOI:10.5530/pres.14.1.12Published:December 2021Type:Original ArticleAuthors:Chinenye J. Ugwah-Oguejiofor, Halilu E. Mshelia, Junaidu Bello, Isah Inuwa, and Abdullahi Sulaiman Author(s) affiliations:Chinenye J. Ugwah- Oguejiofor1,*, Halilu E. Mshelia2,3, Junaidu Bello1, Isah Inuwa1, Abdullahi Sulaiman1 1Department of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences Usmanu Danfodiyo University Sokoto, Sokoto, NIGERIA. 2Department of Faculty of Pharmacy, Cyprus International University, Nicosia, Mersin 10, TURKEY. 3Department of Pharmacognosy and Ethnopharmacy, Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, P.M.B. 2346 Sokoto, NIGERIA. Abstract:Background: Caralluma dalzielii N.E. Brown is commonly referred to as “Karan massalanci” in the Northwest Nigeria where it is used in treating several ailments including pain, diarrhea and stomach issues. Objectives: This study was aimed to investigate the antidiarrheal and antioxidant activities of aqueous aerial parts extract of Caralluma dalzielii. Materials and Methods: The aqueous aerial parts extract of Caralluma dalzielii (CDE) (100, 200 and 400 mg/kg) was evaluated for antidiarrheal properties against gastrointestinal motility, castor oil-induced and prostaglandin-E2 (PGE2) enteropooling models in Wistar rats. Its antioxidant properties were studied by determining the total phenolic content (TPC) using Folin-Ciocalteu reagent, its free radical scavenging activity using 1, 1-Diphenyl-2-Picrylhydrazyl (DPPH) and its ferric reducing antioxidant power (FRAP) assays using potassium ferrocyanide ferric chloride methods. Ascorbic acid was used as the reference. Spasmolytic effect was studied in isolated rabbit jejunum preparations in an organ bath experiment using acetylcholine (ACh). Results: CDE significantly (p<0.05) reduced gastrointestinal transit of charcoal meal and the total number of diarrheal feces in the animals. The total phenolic content was determined to be 36.67±3.33 mg GAE/g. IC50 value of 63.44 mg/mL was calculated in DPPH assay. The FRAP value was found to increase as the concentration of the extract increased. CDE inhibited acetylcholine-induced contraction of the rabbit jejunum in a concentration dependent manner with complete inhibition at 20.48 mg/mL of the extract. Conclusion: The extract of Caralluma dalzielii possesses antidiarrheal activities which may be related to its antimotility, antioxidant and antispasmodic properties. Keywords:Antioxidant, Antispasmodic, Caralluma dalzielii, Gastrointestinal motility, Rabbit jejunum.View:PDF (543.04 KB) Full Text

Antidiarrheal and Cardio-Depressant Effects of Himalaiella heteromalla (D.Don) Raab-Straube: In Vitro, In Vivo, and In Silico Studies.

Himalaiella heteromalla (D.Don) Raab-Straube is a commonly used remedy against various diseases. Crude extract and fractions of H. heteromalla were investigated for a gastrointestinal, bronchodilator, cardiovascular, and anti-inflammatory activities. H. heteromalla crude extract (Hh.Cr) relaxed spontaneous contractions and K+ (80 mM)-induced contraction in jejunum tissue dose-dependently. The relaxation of K+ (80 mM) indicates the presence of Ca++ channel blocking (CCB) effect, which was further confirmed by constructing calcium response curves (CRCs) as they caused rightward parallel shift of CRCs in a manner comparable to verapamil, so the spasmolytic effect of Hh.Cr was due to its CCB activity. Application of Hh.Cr on CCh (1 µM) and K+ (80 mM)-induced contraction in tracheal preparation resulted in complete relaxation, showing its bronchodilator effect mediated through Ca++ channels and cholinergic antagonist activity. Application of Hh.Cr on aortic preparations exhibited vasorelaxant activity through angiotensin and α-adrenergic receptors blockage. It also showed the cardio suppressant effect with negative chronotropic and inotropic response in paired atrium preparation. Similar effects were observed in in vivo models, i.e., decreased propulsive movement, wet feces, and inhibition of edema formation.

Intrathecal Baclofen Monotherapy and Polyanalgesia for Treating Chronic Pain in Patients with Severe Spasticity.

Intrathecal drug delivery is a well evidenced strategy for the treatment of many chronic pain syndromes. While opioids, anesthetics, and ziconotide are the most commonly used agents, intrathecal baclofen (ITB), which is indicated to treat spasticity, is also thought to have some analgesic properties that are poorly understood. These analgesic benefits have been reported with ITB use in treating patients with central neurological disorders who suffer from severe spasticity and chronic pain. Our review aims to characterize ITB's effects on pain, function, and quality of life in patients with severe spasticity.We performed a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. The primary outcome parameters were analgesic relief and functional improvements. Secondarily, quality of life and adverse effects were also recorded. After an initial survey identified 393 studies, 20 studies met final inclusion criteria. Of these, 16 utilized ITB monotherapy and 4 utilized ITB polyanalgesia. Overall, there was a paucity of high-powered studies. Mean titrated ITB doses ranged from 140 to 627.9μg daily. Nineteen studies reported improved pain and spasticity. Seven studies reported improved functional outcomes and quality of life. Our results show that ITB may bean effectiveagent in treatingfor the treatment of chronic pain in patients with severe spasticityindependent of its spasmolytic effects. Although this evidence was largely derived from studies lacking clearly defined outcomes of pain relief, ITB is reasonable to consider for concurrent spasticity and pain management. Well-designed studies are still needed to characterize ITB's analgesic efficacy when used in patients with severe spasticity.

Antiviral Activities of Eucalyptus Essential Oils: Their Effectiveness as Therapeutic Targets against Human Viruses.

Given the limited therapeutic management of infectious diseases caused by viruses, such as influenza and SARS-CoV-2, the medicinal use of essential oils obtained from Eucalyptus trees has emerged as an antiviral alternative, either as a complement to the treatment of symptoms caused by infection or to exert effects on possible pharmacological targets of viruses. This review gathers and discusses the main findings on the emerging role and effectiveness of Eucalyptus essential oil as an antiviral agent. Studies have shown that Eucalyptus essential oil and its major monoterpenes have enormous potential for preventing and treating infectious diseases caused by viruses. The main molecular mechanisms involved in the antiviral activity are direct inactivation, that is, by the direct binding of monoterpenes with free viruses, particularly with viral proteins involved in the entry and penetration of the host cell, thus avoiding viral infection. Furthermore, this review addresses the coadministration of essential oil and available vaccines to increase protection against different viruses, in addition to the use of essential oil as a complementary treatment of symptoms caused by viruses, where Eucalyptus essential oil exerts anti-inflammatory, mucolytic, and spasmolytic effects in the attenuation of inflammatory responses caused by viruses, in particular respiratory diseases.

Spasmolytic Effects of Aphanizomenon Flos Aquae (AFA) Extract on the Human Colon Contractility.

The blue-green algae Aphanizomenon flos aquae (AFA), rich in beneficial nutrients, exerts various beneficial effects, acting in different organs including the gut. Klamin® is an AFA extract particularly rich in β-PEA, a trace-amine considered a neuromodulator in the central nervous system. To date, it is not clear if β-PEA exerts a role in the enteric nervous system. The aims of the present study were to investigate the effects induced by Klamin® on the human distal colon mechanical activity, to analyze the mechanism of action, and to verify a β-PEA involvement. The organ bath technique, RT-PCR, and immunohistochemistry (IHC) were used. Klamin® reduced, in a concentration-dependent manner, the amplitude of the spontaneous contractions. EPPTB, a trace-amine receptor (TAAR1) antagonist, significantly antagonized the inhibitory effects of both Klamin® and exogenous β-PEA, suggesting a trace-amine involvement in the Klamin® effects. Accordingly, AphaMax®, an AFA extract containing lesser amount of β-PEA, failed to modify colon contractility. Moreover, the Klamin® effects were abolished by tetrodotoxin, a neural blocker, but not by L-NAME, a nitric oxide-synthase inhibitor. On the contrary methysergide, a serotonin receptor antagonist, significantly antagonized the Klamin® effects, as well as the contractility reduction induced by 5-HT. The RT-PCR analysis revealed TAAR1 gene expression in the colon and the IHC experiments showed that 5-HT-positive neurons are co-expressed with TAAR1 positive neurons. In conclusion, the results of this study suggest that Klamin® exerts spasmolytic effects in human colon contractility through β-PEA, that, by activating neural TAAR1, induce serotonin release from serotoninergic neurons of the myenteric plexus.

Spasmolytic Effect of Grewia asiatica Fruit Extract on Isolated Smooth Muscles is Mediated via Multiple Pathways.

BackgroundGrewia asiatica Linn, or phalsa, is a commonly consumed fruit in Pakistan. The fruit is employed in the traditional medicine practice of Pakistan as a smooth muscle relaxant in different gastrointestinal (GI) and cardiovascular diseases. In this investigation, we show the antispasmodic and vasorelaxant actions of Grewia asiatica fruit extract. Methods A 70% methanolic crude extract of the plant material was prepared (Ga.Cr). Different isolated GI tissue preparations and endothelium-intact aortas from rats were utilized to observe the pharmacological actions of the extract. Results Ga.Cr, in increasing concentrations, inhibited the spontaneously contracting rabbit jejunum. In an effort to determine the mechanism of this relaxant action, contractions were induced in jejunum and ileum tissues with K+ (80 mM). Ga.Cr was able to only partially inhibit these induced contractions indicating that the mechanism might not be completely through a blockade of Ca2+ channels (CCB). When tested on low K+-(25 mM) sustained contractions, Ga.Cr cumulatively suppressed these contractions (0.1–10 mg/ml), indicating an opening of K+ channels (KCO) as the mechanism. Cromakalim, a standard KCO, was also more specific in blocking low K+-induced contractions. For the effect in aorta tissues, Ga.Cr suppressed the agonist-induced contractions from 0.3 mg/ml to 10 mg/ml. Upon challenge with L-NAME, a nitric oxide (NO) blocker, the extract response curve shifted right, indicating vasodilation was mediated via endothelial NO. Conclusion This study shows that GI antispasmodic and vasodilator activities of Ga.Cr may be mediated via a KCO mechanism in the GI tract and through the release of NO from vascular endothelium.

PD27-11 PRELIMINARY PHARMACOKINETIC DATA OF AN IN VITRO AND ANIMAL STUDY OF A NOVEL INTRAVESICAL SUSTAINED DELIVERY SYSTEM OF LIDOCAINE AND OXYBUTYNIN (TRG-042)

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology (PD27)1 Sep 2021PD27-11 PRELIMINARY PHARMACOKINETIC DATA OF AN IN VITRO AND ANIMAL STUDY OF A NOVEL INTRAVESICAL SUSTAINED DELIVERY SYSTEM OF LIDOCAINE AND OXYBUTYNIN (TRG-042) Boris Chertin, David Dothan, Nadav Malchi, Avi Gordon, and Dan Touitou Boris ChertinBoris Chertin More articles by this author , David DothanDavid Dothan More articles by this author , Nadav MalchiNadav Malchi More articles by this author , Avi GordonAvi Gordon More articles by this author , and Dan TouitouDan Touitou More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002020.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Interstitial Cystitis / Bladder pain syndrome (IC/BPS) is a chronic debilitating condition of unknown etiology. Intravesical lidocaine administration has demonstrated pain relief in patients with IC/BPS. Intravesical administration of Oxybutynin has a well-documented therapeutic effect in patients with urinary bladder disorders due to a direct local anesthetic, antimuscarinic and spasmolytic effect within the bladder wall. However, intravesical use of the both drugs in the clinical practice did not stand the test of time due to rapid dilution and loss of drug with urination requiring multiple administrations. The ability to prolong drug retention in the urinary bladder enhances the bladder wall tissue exposure to adequate therapeutic level of drugs. The aim of this study was to evaluate the efficacy and safety of fixed-dose combination of Lidocaine and Oxybutynin novel polymeric composition forming instantly in the urine a sustained delivery system named TRG-042. METHODS: We have In-Vitro tested release of Lidocaine and Oxybutynin from TRG-042 in artificial urine (AUF) and have quantitatively determined Oxybutynin and Lidocaine concertation utilizing high-pressure liquid chromatography(HPLC). Following the successful In-Vitro study weekly formulation of TRG-042 was instilled into urinary bladder of 6 pigs. All pigs were followed with cystoscopy and US in order to assess the gradual degradation of the intravesical delivery system and to evaluate the response of the bladder over the seven days. Daily blood samples were tested for drug quantitation. Three pigs, who received TRG-042 without Oxybutynin and Lidocaine served as a control. RESULTS: In-Vitro studies have demonstrated Oxybutynin and Lidocaine sustained release over the one-week period coupled with the full degradation of the matrix. None of the animals demonstrated any side effects following instillation. Cystoscopy examination observed gradual disintegration of the TRG-042 over one-week period with no adverse reaction of the bladder mucosa. Plasma concentrations of Oxybutynin and Lidocaine were uniformly high and stable over the one-week study period 1.46+/-0.176 ng/ml and 4.29+/-2.48 ng/ml respectively (mean+/-SEM) with almost undetectable concentration of active metabolite N-desethyloxybutynin (NDO) 0.032+/-0.068 ng/ml. CONCLUSIONS: The In-Vitro and animal data suggest that TRG-042 can safely be used for possible intravesical sustain release of Lidocaine and Oxybutynin in the treatment of BPS/IC. Our preliminary results should be further confirmed in clinical studies. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e448-e448 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Boris Chertin More articles by this author David Dothan More articles by this author Nadav Malchi More articles by this author Avi Gordon More articles by this author Dan Touitou More articles by this author Expand All Advertisement Loading ...

Antispasmodic activity of Warionia saharae Benthem ex Benth. &amp; Coss. on the rabbit and rat jejunums

Context: Warionia saharae Benthem ex Benth. &amp; Coss has been widely used for gastrointestinal problems in Morocco and Algeria. Aims: To explore the possible mechanism for its use to such ailments in order to rationalize some of these folkloric uses. We investigated the aqueous extract of this plant (AqWs) for antispasmodic activity on isolated rat and rabbit jejunums. Methods: To investigate the contractile activity of isolated jejunum preparations of rat and rabbit we had used in vitro techniques. Jejunums were suspended in tissue baths filled with KHB culture medium (37°C) and connected to force transducers. AqWs (0.1–3 mg/mL) was used with or without carbachol (10-6 M), KCl (25 mM), yohimbine (10-5 M), prazosin (10-5 M), propranolol (10-5 M), hexamethonium (10-4 M), atropine (10-6 M), methylene blue (10-5 M), L-NAME (10-4 M) and nifedipine (10-6 M). Results: AqWs at 0.1–3 mg/mL produced a relaxation on basal rabbit contractions with an IC50 = 1.55 ± 0.06 mg/mL. This effect was reversible and was not affected by pretreatment with the inhibitors of α and β adrenergic receptors yohimbine, prazosin and propranolol. The extract had an antispasmodic activity with an IC50 = 1.25 ± 0.02 mg/mL on rat jejunum precontracted with KCl rich medium (25 mM). This result suggests that the extract had a Ca2+ antagonist effect. This was fortified when pretreatment of the intestine with the extract induced a rightward shift in the Ca2+ concentration-response curves. AqWs exhibited also antispasmodic effect on carbachol (10-6 M)-induced contractions of rat jejunums with an IC50 = 1.53 ± 0.04 mg/mL. The extract at 3 mg/mL on rat jejunums pre-incubated with hexamethonium (10-4 M), atropine (10-6 M), and methylene blue (10-5 M), then contracted by KCl, decreased the maximum contraction but not totally like KCL alone without these inhibitors. For the jejunum pre-incubated with L-NAME (10-4 M), the spasmolytic effect of AqWs was comparable with KCL. Conclusions: These results suggest that the myorelaxant and antispasmodic effects are mediated possibly via Ca2+ antagonist, anticholinergic, and guanylate cyclase mechanisms but not by adrenergic and nitric oxide pathway.

Calea ternifolia Kunth, the Mexican “dream herb”, a concise review

Calea ternifolia Kunth (Asteraceae), the “dream herb”, is an important medicinal plant that grows from Mexico to Costa Rica. The plant is highly valued for rituals and for treating several illnesses including anorexia, upset stomach, diabetes, periodic fevers, diarrhea, bile problems, and skin diseases. This comprehensive literature survey on C. ternifolia was performed up to January 2021. Our review focuses on traditional uses, botanical aspects, chemical constituents, quality control tests, as well as pharmacological and toxicological studies. Data were recorded using online scientific databases including Scopus, PubMed, Google Scholar, Taylor and Francis Imprints, National Center for Biotechnology Information, Science Direct, JSTOR, and SciFinder. The information was assembled from research articles, relevant books on herbal medicinal plants and the history of medicinal plants from Mexico, theses, reports, and web pages. The more significant botanical and ethnomedical aspects were recorded including the discovery of the oneirogenic use (enhancer of dreams) of C. ternifolia by the Chontal Indigenous communities in Oaxaca, Mexico. The plant contains sesquiterpenes and flavonoids as the major constituents. Some properties associated with the plant’s traditional uses have been demonstrated including spasmolytic, antidiabetic, antidepressant, anti-inflammatory, and antinociceptive effects. The plant’s toxicity will be discussed in this paper. Solid pharmacological research provided evidence supporting the use of the dream herb for oneiromancy.

Influence of lyophilized Thymus serpyllum L. extracts on the gastrointestinal system: Spasmolytic, antimicrobial and antioxidant properties

In the presented study, polyphenol profile, spasmolytic, antimicrobial and antioxidant properties of lyophilized Thymus serpyllum extracts were examined. The main phenolic acid in the extracts was rosmarinic acid, followed by salvianolic acid I, salvianolic acid K isomer and caffeic acid, whereas chlorogenic acid was detected only in traces; the dominant flavonoids were luteolin 7-O-glucuronide and 6-hydroxyluteolin 7-O-glucoside, while the contents of apigenin glucuronide and 6,8-di-C-glucosylapigenin were significantly lower. All tested extracts have shown spasmolytic effect in a dose-dependent manner on spontaneous contractions, acetylcholine- and potassium chloride-induced contractions; lyophilized extract obtained in maceration has shown significantly better spasmolytic activity. The mentioned extract has shown dose-dependent spasmolytic effect in the model of contractions induced by barium chloride and calcium chloride, as well. Furthermore, lyophilized extracts were effective against Gram-positive bacteria and showed only moderate antifungal activity. Ultrasound-assisted extraction provided extracts with better ability of neutralization DPPH radicals, whereas maceration and ultrasound-assisted extraction approved to be better regarding β-carotene bleaching assay. Due to spasmolytic, antimicrobial and antioxidant properties shown in the present study, polyphenols-rich T. serpyllum extract may be used as adjuvant in therapy of gastrointestinal disorders and infections caused by some of the susceptible pathogens.

Spasmolytic effect of Lonicera japonica extracts on isolated uterus smooth muscle contractions

Introduction: Honeysuckle (Lonicera japonica) is an ornamental flowering plant with numerous traditional medicinal uses. It has been claimed to have anti-spasmodic activities, but only limited studies have been done to support this. The objective of this research was to investigate anti-spasmodic effect of L. japonica flower extract on uterus contractions. Methods: Hydroalcoholic extract was prepared using the maceration technique. In addition, chloroform and ethyl acetate fractions were prepared using a solvent in solvent fractionation technique. Essential oils were collected using the hydro-distillation technique. Rat isolated uterus was suspended in an organ bath and contracted with oxytocin, acetylcholine (ACh), KCl, or application of electrical field stimulation (EFS). The relaxant effects of the extract, its fractions, and nifedipine were examined on uterine contrition induced by the above-mentioned stimuli. Results: Nifedipine in a concentration-dependent manner inhibited uterine contraction induced by oxytocin, KCl, ACh, and EFS. L. japonica flower extract also exhibited an inhibitory effect on the isolated rat uterus. Comparison of the hydroalcoholic extract with its chloroform and ethyl acetate fractions showed that the chloroform fraction was the most potent and the ethyl acetate the weakest part of the plant with antispasmodic activity. The relaxant effect of essential oil had close similarities to that of chloroform extract. Conclusion: Lipophilic compounds isolated by the chloroform partition of crude hydroalcoholic extract of L. japonica flower exhibited the most antispasmodic activity. Ethyl acetate partition of the same extract exhibited the least activity. Therefore, it can be concluded that the spasmolytic constituents of L. japonica flower reside in chloroform partitioning. The nonpolar essential oils may also have a contribution.

Syzygium Samarangense: Review of Phytochemical Compounds and Pharmacological Activities

Jambu semarang (Syzygium samarangense), which belongs to Myrtaceae family, is widely cultivated in Asia and the Pacific region. This review systematically described the scientifically proven information about the plant's phytochemical contents, traditional usage, and pharmacological activities. Elucidated primary and secondary metabolites of S. samarangense mostly belong to flavonoids, phenolic compounds, resorcinol derivatives, acylphloroglucinols, tannins, terpenoids, and sterols. Various parts of the plant have been used traditionally to remedy cold, itches, cracked tongue, dysentery, and diabetes. It is also commonly consumed fresh or processed as wines, jams, nata, vinegar, and jellies. Currently, in vitro and in vivo experiments of the plant extract have demonstrated various pharmacological activities such as antioxidant, antimicrobial, anti-HIV, analgesic, anti-inflammatory, antihyperglycemic, antidiabetic, thrombolytic, spasmolytic, cytotoxic, hepatoprotective, anticancer, anthelmintic, anxiolytic, protease inhibitory, and immunomodulatory effect. Further research in standardization and clinical studies is highly expected for future development.

Cannabinoid Activity-Is There a Causal Connection to Spasmolysis in Clinical Studies?

Cannabinoid drugs are registered for postoperative nausea and emesis, Tourette syndrome and tumor-related anorexia, but are also used for spasticity and pain relief, among other conditions. Clinical studies for spasmolysis have been equivocal and even conclusions from meta-analyses were not consistent. This may be due to uncertainty in diagnostic criteria as well as a lack of direct spasmolytic activity (direct causality). In this review we used the Hill criteria to investigate whether a temporal association is causal or spurious. Methods: A systematic literature search was performed to identify all clinical trials of cannabinoids for spasticity. Studies were evaluated for dose dependency and time association; all studies together were analyzed for reproducibility, coherence, analogy and mechanistic consistency. A Funnel plot was done for all studies to identify selection or publication bias. Results: Twenty-seven studies were included in this meta-analysis. The spasmolytic activity (effect strength) was weak, with a nonsignificant small effect in most studies and a large effect only in a few studies (“enriched” studies, low patient numbers). No dose dependency was seen and plotting effect size vs. daily dose resulted in a slope of 0.004. Most studies titrated the cannabinoid to the optimum dose, e.g., 20 mg/d THC. The effect decreased with longer treatment duration (3–4 months). The spasmolytic effect is consistent for different European countries but not always within a country, nor is the effect specific for an etiology (multiple sclerosis, spinal cord injury, others). For other criteria like plausibility, coherence or analogous effects, no data exist to support or refute them. In most studies, adverse effects were frequently reported indicating a therapeutic effect only at high doses with relevant side effects. Conclusions: Current data do not support a specific spasmolytic effect; a general decrease in CNS activity analogous to benzodiazepines appears more likely. Whether individual patients or specific subgroups benefit from cannabinoids is unclear. Further studies should compare cannabinoids with other, nonspecific spasmolytic drugs like benzodiazepines.

Investigation of antinociceptive, antipyretic, antiasthmatic, and spasmolytic activities of Brazilian Cannabis sativa L. roots in rodents

Ethnopharmacological relevanceMany studies are performed with the aerial parts of Cannabis sativa L. (Cannabaceae). However, roots remain poorly studied, despite citations in the scientific literature. The C. sativa roots are indicated for the treatment of pain, inflammation, fever, among other health problems.Aim of the study: This study aimed to evaluate the antinociceptive, antipyretic, antiasthmatic, and spasmolytic activities of C. sativa roots in experimental models using mice and rats. Material and methodsThe chemical composition of the aqueous extract of C. sativa roots (AECsR) was evaluated by LC-MS. The antinociceptive activity was assessed in mice by the induction of writhing with acetic acid, paw licking with formalin, and reactivity in the hot plate test. Fever was induced by the administration of a suspension of Saccharomyces cerevisiae in young rats. The asthmatic activity was performed with ovalbumin (OVA)-immunized mice with cellular and histological analysis. Finally, the spasmolytic activity was performed using mice isolated trachea. For in vivo studies, the doses were 12.5, 25, or 50 mg/kg whereas for in vitro, the concentration of AECsR was 729 μg/mL. ResultsFrom the LC-MS data, we identified p-coumaroyltyramine, feruloyltyramine canabissativine in AECsR. The extract promoted a reduction of writhing in all tested doses (12.5, 25, or 50 mg/kg). Similarly, it reduced the pain in the formalin test at doses of 12.5 and 50 mg/kg (first phase) and 12.5 and 25 mg/kg (second phase). In the hot plate test, the doses of 12.5, 25, and 50 mg/kg promoted antinociceptive effect at different times, and the lowest dose maintained its action in the analyzes performed at 60, 90, and 120 min after administration. The anti-inflammatory activity of AECsR was observed in the mouse model of asthma, reducing the total leukocyte count in the bronchoalveolar fluid (BALF) at a dose of 25 mg/kg, as well as reducing eosinophilia in all tested doses (12.5, 25, and 50 mg/kg). Histological analysis of lungs stained with H&E and PAS showed a reduction in the number of inflammatory cells in the perivascular and peribronchial region, as well as reduced mucus production. ConclusionThe results suggest that AECsR promotes pain control, either by a central or inflammatory mechanism, and has antiasthmatic activity. However, there was no antipyretic or spasmolytic effect.

Levosimendan as a therapeutic strategy to prevent neuroinflammation after aneurysmal subarachnoid hemorrhage?

BackgroundPoor patient outcomes after aneurysmal subarachnoid hemorrhage (SAH) occur due to a multifactorial process, mainly involving cerebral inflammation (CI), delayed cerebral vasospasm (DCVS), and delayed cerebral ischemia, followed by neurodegeneration....

The Role of K+, Ca2+ channels, Some Endothelium Hyperpolarizing Factors in Taurine Induced Vasorelaxation in Rats Aorta

The current study included the relaxant effect of taurine on rat’s aortic rings and the mechanism behind this relaxation. Taurine produced a potent spasmolytic effect on aortic rings at concentrations from zero to 80 mM. The results of K+ channel subtypes using specific blockers indicated that the Kv channel has a considerable role in taurine-induced relaxation, while KATP has a limited role, Exposure of aortic rings to combinations of two K+ blockers showed that KCa, Kv, and KIR play important role in taurine mediated relaxation. The endothelium-derived hyperpolarizing factors used showed responses to a variable extent in taurine mediated relaxation; since NO and cGMP played a major role whereas PGS played a minor role in taurine mediated relaxation. Finally, the results also indicated that taurine-mediated relaxation is endothelium-dependent.

Argemone mexicana extract alleviates gastrointestinal disorders by stimulating muscarinic receptors and blocking voltage-gated L-type calcium channels

Objective: To investigate the pharmacological potential of Argemone mexicana in treating constipation and emesis by using in vitro and in vivo models. Methods: The spasmogenic and spasmolytic effects were evaluated on isolated rabbit jejunum fragments loaded in a tissue organ bath. The response was recorded with an isotonic transducer attached with Power Lab Data Acquisition System. The laxative and antiemetic activities were assessed in BALB-c mice and poultry chicks challenged with carbamylcholine and copper sulphate stimulated emesis, respectively. Results: The total phenolic and total flavonoids contents of the extract were (267.75 ± 5.77) mg GAE/g and (73.86 ± 6.01) mg QE/g, respectively. Argemone mexicana extract exerted spasmogenic effect on isolated rabbit jejunum segments with an EC50 value of 0.016 mg/ mL, which was blocked by atropine (0.3 μM). Argemone mexicana extract exerted spasmolytic effect in atropine treated jejunum fragments with an EC50 value of 2.185 mg/mL. Furthermore, Argemone mexicana extract relaxed potassium (80 mM)-induced contractions (EC50: 9.07 mg/mL), similar to a standard drug verapamil. The calcium channel blocker activity was confirmed by a rightward shift of concentration-response curve of calcium in the presence of Argemone mexicana extract (1-5 mg/mL) and verapamil (0.1-1 μM). In addition, the extract increased the distance travelled by a charcoal in the gastrointestinal tract and exhibited antiemetic effect on copper sulphate induced emesis in chicks. Conclusions: Argemone mexicana shows cholinergic agonist and calcium channel blocker activities, as well as antiemetic effect. It may be used as a potential agent for treating gastrointestinal disorders.

Vasorelaxation in rat pulmonary artery induced by the monoterpene thymol: evaluation of the endothelium derived relaxant factors dependence

Thymol and carvacrol are the main compounds found in Lippia mycrophylla essential oil (LM-OE) and have presented some spasmolytic effects. This work was designed to explore a possible vasorelaxant effect of LM-OE and its major monoterpenes constituents on rat pulmonary artery. For that, the organ was in vitro stimulated with phenylephrine (Phe) 3 mM and over the tonic contraction the relaxant effect of LM-OE, carvacrol and thymol was observed in both intact and denuded-endothelium. Moreover, atropine, L-NAME, indomethacin, 2,3-O-isopropylidene adenosine, H-89 and Y-27632 were incubated before the relaxant curve of thymol over Phe-tonic contraction. Furthermore, the effects of thymol on KCl 30 or 80 mM and S-(−)-Bay K8644-induced tonic contractions were evaluated, as well as its inhibitory effect on CaCl2-induced cumulative contractions. LM-OE, carvacrol and thymol presented relaxant effect on pulmonary artery, thymol was the most potent and its relaxant potency in intact-endothelium preparations was reduced by atropine, L-NAME, indomethacin, 2,3-O-isopropylidene adenosine and H-89, despite there was not change on its maximum relaxat effect. Also, the monoterpene relaxed equipotently KCl 30 or 80 mM pre-contracted pulmonary artery, antagonized CaCl2-induced cumulative contractions and relaxed S-(−)-Bay K8644 pre-contracted organ. Ultimately, thymol relaxant potency was not modified by Y-27632. Therefore, thymol acts by endothelium-dependent and independent mechanisms, possibly positively modulating the endothelial cholinergic pathway, prostanoids release and further activation of AC/PKA and also inhibiting Ca2+ influx through CaV.

In vitro and in vivo biological approach to validate folkloric claims of Trianthema triquetra Rottler &amp; Willd

Trianthema triquetra Rottler &amp; Willd (Tt.Cr) is used in traditional practices as a remedy for various ailments. Hence current research was commenced to authenticate the folkloric uses. To discover spasmolytic potential, Tt.Cr was applied to isolate jejunum, while isolated tracheal and aorta tissues were used to determine the tissue relaxing properties of the extract. Anti-lipoxygenase activity was determined in vitro using Baicalein as standard. In vivo testing was carried to examine the potentiality of the herb to treat pyrexia and pain. Tt.Cr showed dose-dependent (0.01 - 3.0 mg/ml) spasmolytic effects in jejunum tissues and relaxed K+ (80 mM)-induced spasm and triggered rightwards shift of Ca+2 concentration-response curves. Carbachol (1μM)- together with K+ (80 mM) - induced tracheal spasm was also relaxed by Tt.Cr (0.01 to 1.0 mg/ml). Additionally, Tt.Cr (0.01 - 1.0 mg/ml) relaxed phenylephrine (1 μM) and K+ (80 mM) - treated constricted rabbit aorta. Tt.Cr (0.5 mM) inhibited lipoxygenase enzyme. Tt.Cr (80 mg/kg) settled pyrexia in rabbits comparable to aspirin and prolonged tail deflection time in mice (100 mg/kg) hence proving analgesic activity. The Tt.Cr demonstrated antispasmodic, bronchodilation and vasodilation properties probably by blocking calcium channels. These outcomes generate logic behind ancient application of herb for numerous ailments such as asthma, cough, heart problems and spasm.