Muscle Relaxant Effects Research Articles

Effectiveness of progressive muscle relaxation on sleep disturbance in athletes

Background: Athletes have general complaints about sleep disturbance which is important for body recovery, healthy brain and body functions, tissue wear and tear, and the body's immune system. Objective: To determine the effectiveness of Progressive Muscle Relaxation (PMR) on sleep disturbance in athletes. Methodology: N=24 athletes aged 18 to 36 years participating in a competition were included in a randomized controlled trial. Athletes who were training for a competition, aged between 18 -and 36 years, and athletes with sleep disturbance score (SDS) falling above 4 on the Athletic Sleep Screening Questionnaire were included. Athlete sleep screening questionnaire (ASSQ) was used to assess sleep disturbance score (SDS). Athletes were randomly assigned to the experimental (n=12) and control (n=12) groups. The experimental group was given progressive muscle relaxation and re-assessed the next day for SDS. Results: The pre-post analysis showed that progressive muscle relaxation reduced the athletes' sleep disturbance score significantly one day after the intervention with a large effect size (p=0.006 Cohen's d= 1.44) in the experimental group. The mean of the mean differences of SDS of both groups were compared which showed a group had a significantly improved sleep disturbance score compared to a control group with a large effect size. (Mean= 1.41 ±1.44 v/s 0.00±1.85, p≤ 0.01, Cohen's d= 1.66). Conclusion: Progressive Muscle Relaxation exercises can be a non-pharmacological method to help athletes sleep by simple head-to-toe muscles contract and relax technique. Clinical Trail No: NCT05695092

Progressive Muscle Relaxation Reduces Blood Pressure in Older Adults with Hypertension

Introduction: The physiological aging process in older adults may lead to various disturbances in the cardiovascular system, including hypertension. One approach to controlling blood pressure is through progressive muscle relaxation therapy. This study aimed to investigate the effect of progressive muscle relaxation on blood pressure in older adults with hypertension at the Social Service Unit for Older Adults in Blitar and Nursing Home in Tulungagung in 2023. Methods: This study employed a quasi-experimental method with a one-group pre-post test design. The population consisted of all older adults with hypertension at the research site in 2023, totaling 80 individuals. Purposive sampling was used to recruit the samples of 39 participants. Observation sheets and a sphygmomanometer were utilized for data collection. Result: The results showed that before receiving progressive muscle relaxation therapy, most participants had stage-1 hypertension, with 23 participants (59%), and stage-2 hypertension, with 16 participants (41%). After the therapy, the majority of participants were included in the stage-1 hypertension category, with 26 participants (67%), and prehypertension, with 5 participants (13%). The Wilcoxon test showed a significant value of ρ = 0.000 < α = (0.05), indicating the effect of progressive muscle relaxation therapy on blood pressure. This means that regular therapy sessions may lead to better blood pressure control in hypertensive patients. Conclusion: Progressive muscle relaxation therapy can increase endorphin hormone production and reduce stress levels, thereby stabilizing blood pressure.

Pengaruh Progressive Muscle Relaxation terhadap Tingkat Insomnia pada Lansia di Panti Wredha Maria Sudarsih

Abstract Background: The elderly experience many changes that cause sleep pattern disturbances, namely insomnia. The technique used to treat insomnia nonpharmacologically is progressive muscle relaxation. Objectives: This study aims to determine the effect of progressive muscle relaxation on insomnia level of the elderly at Panti Wredha Maria Sudarsih. This study is quantitative research using pre-experimental design with one group pretest-posttest. The study was conducted in Panti Wredha Maria Sudarsih. The time of the study was conducted in April 2023-March 2024. Methods: Data collection methods are using interview, questionnaire, observation, and documentation. The number of samples was 27 respondents. The instrument used to measure insomnia level is the insomnia severity index. Progressive muscle relaxation is carried out for 20-30 minutes per session with a frequency of 3 times a week for 8 therapy sessions. The data analysis technique used paired sample t-test. The majority of the sample is old elderly with an age range of 75-90 years (63,0%), don’t have comorbidities (51,9%), and have educational levels, namely no school, junior high school graduate, and high school graduate (25,9%). Results: The results of data analysis obtained t=13,454, p=0,000. Conclusion: There is an effect of providing progressive muscle relaxation on insomnia level of the elderly at Panti Wredha Maria Sudarsih. Therefore, progressive muscle relaxation techniques are recommended in the elderly to reduce the level of insomnia. Keywords: Progressive Muscle Relaxation, Insomnia Level, Elderly

Effect of Deep Breathing Relaxation and Progressive Muscle Relaxation on Blood Pressure

Hypertension, characterized by diastolic pressure exceeding 90 mmHg and systolic pressure surpassing 140 mmHg, poses a significant health challenge often addressed through pharmacological antihypertensive therapy. This research endeavors to evaluate the impact of complementary interventions, specifically deep breathing relaxation and progressive muscle relaxation, on reducing blood pressure among hypertensive patients within the operational domain of the Kertasemaya Community Health Center in the Indramayu Regency in 2023. Adopting a Quasi-Experimental Design with a Pretest-Posttest and Control Group paradigm, the study engaged a cohort of 70 respondents stratified into intervention and control groups. The intervention group underwent a combined therapy of deep breathing relaxation and progressive muscle relaxation, followed by a meticulous post-test for final observations. Meanwhile, the control group underwent an initial blood pressure measurement (pre-test), a relaxation period of 15-30 minutes, and concluded with a post-test for final measurements. The study revealed a statistically significant influence (p=0.013) on average blood pressure within the intervention group compared to the control group. This disparity was observed both before and after the implementation of deep breathing relaxation and progressive muscle relaxation techniques among hypertensive respondents. These findings underscore the potential efficacy of non-pharmacological interventions in mitigating hypertension and enhancing patient well-being. The combination of deep breathing relaxation and progressive muscle relaxation emerges as a highly effective strategy in reducing blood pressure among hypertensive individuals. This integrative therapeutic approach showcases promising potential for promoting cardiovascular well-being, offering a valuable non-pharmacological avenue for hypertension management

Effect Of Progressive Muscle Relaxation Therapy And Slow Deep Breathing On Blood Pressure Of Elderly With Hypertension

Hypertension is one of the degenerative diseases that often appear in the elderly. This starts with a person's inability to control or maintain a stable condition of blood pressure in the body. The frequent visits of the elderly to the elderly Posyandu in Janti village with complaints and blood pressure above normal reflect the lack of efforts of the elderly in controlling or stabilizing blood pressure in the body. The aim of the study was to determine the effect of progressive muscle relaxation therapy andslow deep breathing on hypertension elderly blood pressure. Research design Like an experiment with a sample of 62 elderly people with hypertension, selected by purposive sampling technique which was then divided into 2 groups, 31 people in the treatment group were given a combination of progressive muscle relaxation andslow deep breathing, and 31 people in the control group were given therapyslow deep breathig. Data analysis used the Paired T-Test and Independent T-Test. The results of the study in the treatment group before being given the intervention obtained an average of 146.00 mmHg systolic, 91.52 mmHg diastolic (degree 1 hypertension). Independent T-Test analysis found on systolic and diastolic blood pressure, pulse value ρ = 0.000 < α = 0.05, meaning that there is a combination effect of progressive muscle relaxation and music therapy on blood pressure and pulse. Progressive muscle relaxation therapy and slow deep breathing can reduce blood pressure in elderly people with hypertension. It is hoped that this therapy can be used as a non-pharmacological therapy to help lower blood pressure in hypertensive patients in addition to using pharmacological therapy.

Treatment-resistant hiccups during general anesthesia possibly caused by remimazolam: a case report

BackgroundPrevious reports have described hiccups during general anesthesia that were possibly induced by drugs, including benzodiazepines. However, there are few reports of hiccups caused by remimazolam.Case presentationA 75-year-old woman underwent corneal transplantation under general anesthesia with remimazolam. She presented with hiccups once the effects of muscle relaxants used during induction wore off, which persisted even after various treatments, such as the administration of antipsychotic drugs. However, when remimazolam administration was terminated after surgery to awaken the patient, the hiccups stopped and did not recur after extubation. Evaluation of predicted blood levels of remimazolam suggests that higher levels of remimazolam might cause hiccups.ConclusionRemimazolam might induce hiccups during general anesthesia. Anesthesiologists should consider administering muscle relaxants or changing the anesthetic in cases of refractory hiccups under general anesthesia.

COMPARISON BETWEEN NEBULISATION OF MGSO4 20 MG/KGBW WITH KETAMINE 0.5 MG/KGBW ON THE INCIDENT OF POST-OPERATIVE SORE THROAT DUE TO ENDOTRACHEAL INTUBATION IN PATIENTS UNDERGOING GENERAL ANESTHESIA IN DR. HASAN SADIKIN HOSPITALS BANDUNG

Post Operative Sore Throat (POST) is a Symptoms often experienced by patients after surgery under general anesthesia and endotracheal intubation. The incidence of POST is between 21-71.8. POST causes discomfort to patients which can prolong hospital stay. In this study, a comparison was made between MgSO4 nebulization 20 mg/ KgBW and ketamine nebulization 0.5 mg/ KgBW on the incidence of POST after general anesthesia at RSUP Dr. Hasan Sadikin Bandung . This study used a double blind randomized controlled trial design. 72 elective surgery patients were randomly divided into 2 groups. Group M was given MgSO4 nebulization while group K was given ketamine nebulization. Nebulization was performed 15 minutes before induction of general anesthesia. POST monitoring was performed at 1, 4 and 24 hours after extubation using POST scoring. In this study, it was found that the incidence of POST in group M, namely the 1st hour of 13.5, the 4th hour of 10.8 and the 24th hour of 0 was lower than that in group K, namely the 1st hour of 28.5, the 4th hour of 32.5 and the 24th hour of 0. Statistical test results p0.033 showed a significant difference in group M better than group K at the 4th hour in reducing the incidence of POST. MgSO4 and ketamine have antinociceptive and anti-inflammatory effects with the mechanism of action of blocking NMDA receptors that inhibit calcium influx that avoids central sensitization. MgSO4 also has a muscle relaxing effect and reduces airway mucus secretion, thus reducing the risk of trauma during endotracheal intubation. The conclusion of this study is that MgSO4 nebulization shows a lower incidence of POST than ketamine nebulization.

Muscle relaxant and antipyretic effects of pentacyclic triterpenes isolated from the roots of Diospyros lotus L

The present article describes the muscle relaxant and antipyretic effects of pentacyclic triterpenes, oleanolic acid (OA), ursolic acid (UA) and betulinic acid (BA) isolated from roots of Diospyros lotus in animal models. The muscle relaxant effects of isolated pentacyclic triterpenes were determined by chimney and inclined plane tests. In the chimney test, pretreatment of pentacyclic triterpenes evoked significant dose dependent influence on muscle coordination. When administered intraperitoneally (i.p.) to mice at 10 mg/kg for 90 min, OA, UA, and BA exhibited muscle relaxant effects of 66.72 %, 60.21 %, and 50.77 %, respectively. Similarly, OA, UA, and BA (at 10 mg/kg) illustrated 65.74 %, 59.84 % and 51.40 % muscle relaxant effects in the inclined plane test. In the antipyretic test, significant amelioration was caused by pretreatment of all compounds in dose dependent manner. OA, UA, and BA (at 5 mg/kg) showed 39.32 %, 34.32 % and 29.99 % anti-hyperthermic effects, respectively 4 h post-treatment, while at 10 mg/kg, OA, UA, and BA exhibited 71.59 %, 60.99 % and 52.44 % impact, respectively. The muscle relaxant effect of benzodiazepines is well known for enhancement of GABA receptors. There may exist a similar mechanism for muscle relaxant effect of pentacyclic triterpenes. The in-silico predicted binding pattern of all the compounds reflects good affinity of compounds with GABAA receptor and COX-2. These results indicate that the muscle relaxant and antipyretic activities of these molecules can be further improved by structural optimization.

Effects of progressive muscle relaxation exercises on the vital signs and fatigue in kidney transplant patients: a randomized controlled trial.

Multiple effective nursing interventions are needed to manage deviations from normal vital signs and fatigue experienced by kidney transplant patients. In this study, we investigated the effect of progressive muscle relaxation (PMR) exercises on vital signs and fatigue in kidney transplant patients. We conducted a randomized controlled experimental study with 52 patients (intervention = 26, control = 26) who underwent kidney transplantation at a university hospital in Turkey and met the inclusion criteria. The "Descriptive Characteristics Form", "Vital Signs Monitoring Form", and "Fatigue Severity Scale" were used to record data on the patients. Then, the patients in the intervention group (baseline assessment) were trained to perform PMR exercises, asked to practice, and followed up (first follow-up). Patients were recommended to perform PMR exercises for 20min every day for four weeks. The second follow-up in the second week after discharge and the third follow-up at the end of the fourth week were performed in the outpatient clinic. We found that the pulse rate, body temperature, and arterial blood pressure decreased over time and oxygen saturation increased in the patients of the intervention group. The PMR exercises decreased fatigue in these patients. The arterial blood pressure and oxygen saturation values differed significantly across different time points among the patients in the control group. The difference in the scores of fatigue severity between the pre-follow-up and the third follow-up in the control group was not significant. PMR exercises were found to be an effective nursing intervention in regulating vital signs and reducing fatigue in renal transplant patients.

The Effect of Progressive Muscle Relaxation (PMR) on Stress Level of Diabetes Mellitus Patients

The Effect of Progressive Muscle Relaxation (PMR) on Stress Level of Diabetes Mellitus Patients

Relaksasi Otot Progresif dalam Manajemen Nyeri Pembedahan Ortopedi

This writing aims to determine the effect of progressive muscle relaxation as a non-pharmacological therapy that can be used as a complementary or additional therapy in pain management in patients after orthopedic surgery. The method used was a systematic search for articles through the PubMed, Science Direct, Proquest, and Francis Taylor databases and published from 2013 to 2023 using the keywords "progressive muscle relaxation" AND "Pain" OR "Postoperative Pain" AND "Orthopedics surgery." From the search results, 11,262 articles were obtained, and it was determined that five articles that met the inclusion criteria were RCT (Randomized Control Trial) research studies. The study's results showed that 521 patients who met the inclusion criteria reported significant pain differences between the intervention and control groups. The intervention group given progressive muscle relaxation showed better pain reduction than the control group. The heterogeneity of study participants included patients after lumbar surgery (lumbar disc herniation, microdiscectomy, laminectomy), after TKA (Total Knee arthroplasty), and after tibiofibular fracture surgery. Four research articles provided progressive muscle relaxation interventions without combining them with other interventions, while one research article combined progressive muscle relaxation with other interventions in the form of physiotherapy. In conclusion, the latest evidence from several studies shows the role of progressive muscle relaxation as an additional or complementary therapy in managing pain in patients after orthopedic surgery, whether given together or without in combination with other interventions, shows positive results in helping reduce pain. Keywords: Pain, Orthopedic Surgery, Progressive Muscle Relaxation

Role of Cinnamomum verum leaves in the management of Vascular dementia: A comprehensive overview

Spices are utilized for both culinary and medicinal purposes and have been for a very long time originating from Sri Lanka and southern India, Cinnamomum verum may also be found in other Asian, Caribbean, Australian, and African countries. The principal compounds contained are Cinnamaldehyde and Eugenol, both of which have unique medicinal qualities in the leaves of Cinnamomum verum. Cinnamonaldehyde (CA), a bioactive phytochemical offer therapeutic advantages against the beginning of cardiovascular illnesses. Eugenol is an organic compound found in the leaves of Cinnamomum verum. Eugenol has antihypercholesterolemic and antiatherogenic effects. Eugenol's smooth muscle relaxant effect is due to its inhibition of receptor-operated and voltage-sensitive channels. Endothelial cells create nitric oxide (NO), which relaxes blood vessels. Eugenol has substantial anti-inflammatory properties. The antipyretic activity of eugenol is well recognized, since it reduces fever by reducing prostaglandin and sodium archidonate synthesis. Eugenol's hydrophobic nature allows it to pass the blood-brain barrier and enter the brain. Eugenol protects neuronal cells against the oxidative and excitotoxic effects of N-methyl-D-aspartate (NDMA). Eugenol has neuroprotective properties in hippocampal tissues due to its capacity to reduce brain-derived neurotrophic factor (BDNF) and postpone amyloid β -peptide (A- β) induced cell death via abnormal Ca2+ blocking. Anti-hypertensive property of Eugenol is known as it has the ability to activate TRPV channels and to relax endothelium-depleted arteries. Eugenol, which is found in Cinnamomum verum leaves, has been shown to be beneficial in the control of hypertension and so may be beneficial in the management of vascular dementia.

THE EFFECT OF PROGRESSIVE MUSCLE RELAXATION THERAPY IN DIABETES MELLITUS PATIENTS ON REDUCING BLOOD SUGAR LEVELS

The increase in the number of Diabetes Mellitus sufferers will have an impact on physical and psychological conditions. The physical impacts are diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy. Meanwhile, the psychological impact is the emergence of anxiety, anger, grief, shame, guilt, loss of hope, depression, loneliness, and hopelessness towards treatment. One non-pharmacological therapy to overcome the above phenomenon is the application of progressive muscle relaxation. Progressive muscle relaxation carried out continuously has a good impact on reducing blood glucose levels in Diabetes Mellitus patients. This study aims to identify a decrease in blood glucose levels in Diabetes Mellitus patients by implementing Progressive Muscle Relaxation. The research method used is a descriptive case study. The population and sample in this study was 1 Diabetes Mellitus patient. The results of the study showed that the patient experienced a decrease in blood glucose levels after Progressive Muscle Relaxation from 372 mg/dl to 240 mg/dl. This research concludes that there is an effect of Progressive Muscle Relaxation on reducing blood glucose levels in Diabetes Mellitus patients.

Comparison of Effects of Sugammadex andNeostigmine on Postoperative Neuromuscular Blockade Recovery in Patients with Interstitial Lung Diseases Undergoing Transbronchial Cryobiopsy: A Randomized Trial.

BACKGROUND While many studies have been conducted on sugammadex sodium and neostigmine in patients undergoing general anesthesia, few have explored their effects in patients with interstitial lung diseases (ILDs). MATERIAL AND METHODS Sixty-three patients who underwent transbronchial cryobiopsy under general anesthesia were enrolled in a prospective randomized study. The patients were randomly divided into 2 groups: neostigmine combined with atropine group (group C, n=32) and sugammadex group (group S, n=31). Induction and maintenance of anesthesia were the same in both groups. Patients received rocuronium during anesthesia. At the end of the procedure, when the T2 of the train-of-four stimulation technique (TOF) monitoring appeared, neostigmine 0.04 mg/kg combined with atropine 0.02 mg/kg was injected intravenously in group C, and sodium sugammadex 2 mg/kg was injected intravenously in group S. Time from administration of muscle relaxant antagonist to recovery of TOF ratio (TOFr) to 0.9 and extubation time were recorded. The residual rate of neuromuscular blockade at 1, 3, 5, 7, and 10 min after extubation was calculated. RESULTS Compared to group C, group S had a significantly shorter recovery time of TOFr to 0.9 (4.0[2.0] min vs 14.0[11.0] min, P<0.001) and extubation time (4.0[3.0] min vs 11.0[7.0] min, P<0.001). The residual rate of neuromuscular blockade was remarkably lower in group S than in group C at 3, 5, and 7 min after extubation (3.2% vs 31%, 0% vs 25%, 0% vs 6%, P<0.05). CONCLUSIONS Sugammadex is more effective than neostigmine in reversing the muscle-relaxant effect of rocuronium bromide in patients with ILDs.

The Effectiveness of Warm Water Foot Soaks and Progressive Muscle Relaxation to Reduce Blood Pressure Among Patients with Hypertension in Cihanjuang Rahayu Village, West Bandung, Indonesia

One of the highest cardiovascular diseases that cause premature death is hypertension. In addition to pharmacological therapy used to maintain blood pressure ≤ 140/90 mmHg, there are also non-pharmacological therapies, namely warm water foot soak and progressive muscle relaxation. This study aims to determine the effect of a warm water foot soak and progressive muscle relaxation therapy in hypertensive patients. The design used in this research is Quasi-Experiment, with the design with the pretest-posttest nonequivalent control group. The sampling technique is consecutive sampling, the number of samples was 20 patients with hypertension. The tests used were Paired T-test and Independent T-test. The results of the study 10 respondents who had received hydrotherapy soaked in warm water foot got an average systolic and diastolic value of 131,07 mmHg and 82,92 mmHg, while the other 10 respondents who received progressive muscle relaxation therapy received a mean of systolic and diastolic value 131,83 mmHg and 82,93 mmHg. Based on independent t-test significant with p-values of 0,872 and p-values &gt; 0,993. There is no difference in effectiveness between interferences of a warm water foot soak and progressive muscle relaxation to decrease systolic and diastolic blood pressure among patients with hypertension in Cihanjuang Rahayu Village, West Bandung.

Analgesic and Psychotropic Effects of a New Bradykinin Antagonist.

A bradykinin B1 receptors antagonist PAV-0056, an 1,4-benzodiazepin-2-one derivative, intragastrically administrated to mice at doses of 0.1 and 1 mg/kg causes analgesia in the "formalin test" not inferior to that of diclofenac sodium (10 mg/kg) and tramadol (20 mg/kg). PAV-0056 at doses of 0.1 and 10 mg/kg has no anxiolytic and central muscle relaxant effects in mice and does not damage the gastric mucosa in rats. Based on the results of the conditioned place preference test, PAV-0056 also does not induce addiction in mice.

The Effect of Progressive Muscle Relaxation on the Value of Ankle Brachial Index and Foot Sensitivity in Patients with Diabetes Mellitus

Diabetes mellitus (DM) is a global health threat due to many other health risks such as kidney failure, heart disease, stroke and even serious injuries that can cause complications. One of the complications is peripheral neuropathy nerve damage that causes diabetic ulcers so that there is a risk of decreased foot sensitivity and changes in ankle brachial index values in diabetics. Progressive muscle relaxation technique is one of the actions that can affect the hypothalamus to regulate and reduce the activity of the sympathetic nervous system to provide direction by moving the feet slowly and regularly. Objective: to determine the effect of progressive relaxation techniques on the value of ankle brachial index and foot sensitivity in patients with diabetes mellitus. Methods: This study used quasi experiment method with pre test and post test design approach with control group. The population of DM patients was 120 respondents, then the sample was taken using non-probability sampling and based on inclusion and exclusion criteria. Sampling using total sampling with the number of respondents 15 intervention groups and 15 control groups. Analysis using the t-test. Results: The results of the study on the ABI value obtained a p-value of 0.02 in the intervention group and a p-value of 0.414 in the control group while the foot sensitivity value obtained a p-value of 0.01 in the intervention group and 0.07 in the control group. Conclusion: This shows that there is an increase in ABI values and foot sensitivity in patients with diabetes mellitus. The progressive relaxation technique can be used as an intervention to prevent diabetic foot ulcers.

Effect of Thoracoscopic Surgery under Spontaneous Respiration on Inflammatory Indicators and Postoperative Complications in Elderly Patients with Primary Spontaneous Pneumothorax

Background: In thoracoscopic surgery under spontaneous respiration, patients could breathe spontaneously during surgery without the need for mechanical ventilation via tracheal intubation. This technique can effectively avoid the injuries caused by tracheal intubation and mechanical ventilation and the side effects of muscle relaxants, thus reducing postoperative complications and benefitting patients. This study aims to explore the application of thoracoscopic surgery under spontaneous respiration in the elderly with primary spontaneous pneumothorax (PSP) and its effect on inflammatory indices and postoperative complications. Methods: The medical records of 181 elderly patients with PSP who underwent thoracoscopic surgery in our hospital from June 2021 to June 2022 were chosen for retrospective analysis. After excluding 15 patients who did not meet inclusion criteria, 80 patients receiving spontaneous respiration via laryngeal mask ventilation were included in the study group and 86 patients undergoing pulmonary ventilation via single-lumen tracheal intubation were included in the control group in accordance with the different schemes used in the surgery. Preoperative anaesthesia induction, surgical and hospitalisation times were compared, and the haemodynamics and inflammatory indices and complication incidences of the two groups were analysed. Results: Recovery time and hospitalisation time significantly differed between the two groups (p &lt; 0.001). Compared with the control group, the study group had significantly lower mean arterial pressure at T2 and faster heart rates at T2 and T3 (p &lt; 0.001). At T5, T6 and T7, the levels of interleukin-6, interleukin-8 and C-reactive protein in the study group were significantly lower than those in the control group (p &lt; 0.05). The incidence of intraoperative and postoperative complications did not significantly differ between the two groups (p &gt; 0.05). Conclusion: Thoracoscopic surgery under spontaneous respiration is safe and effective in the treatment of elderly patients with PSP. It reduces the levels of inflammatory factors and accelerates postoperative rehabilitation, showing certain value for clinical promotion.

Mechanisms involved in the muscle relaxing effects of STW 5 in guinea pig stomach.

The herbal preparation STW 5 ameliorates functional dyspepsia partly by relaxing smooth muscle of the proximal stomach, thus improving gastric accommodation. We explored the unknown pathways responsible for this effect by testing targets known to modulate gastric smooth muscle relaxation. STW 5-induced relaxation of smooth muscle strips from guinea pig gastric corpus before and after pharmacological interventions were recorded with force transducers in an organ bath. ORAI1 mRNA expression was tested in the proximal stomach. Blockade of Ca2+-activated K+ and Cl- channels, voltage-gated L- or T-type Ca2+ channels, TRPA1-, TRPV1-, adenosine or 5-HT4 receptors, antagonizing ryanodine receptors, inhibiting cyclooxygenase or sarcoplasmic reticulum calcium ATPase did not affect STW 5-evoked relaxation. Likewise, protein-kinase A or G were not involved. However, the relaxation evoked by STW 5 was significantly reduced by phorbol-12-myristat-13-acetat, an activator of protein-kinase C, by 2- aminoethyldiphenylborinate, an inhibitor of the IP3 receptor-mediated Ca2+ release from the sarcoplasmic reticulum or by SKF-96365, a nonselective store-operated calcium entry (SOCE) blocker. Furthermore, the mixed TRPC3/SOCE inhibitor Pyr3, but not the selective TRPC3 blocker Pyr10, reduced the effect of STW 5. Finally, BTP2, a potent blocker of ORAI-coupled SOCE, almost abolished STW 5-evoked relaxation. Expression of ORAI1 could be demonstrated in the corpus/fundus. STW 5 inhibited SOCE, most likely ORAI channels, which are modulated by IP3- and PKC-dependent mechanisms. Our findings impact on the design of drugs to induce muscle relaxation and help identify phytochemicals with similar modes of actions to treat gastrointestinal disturbances.

Cannabinoid-Induced Stereoselective Inhibition of R-S-Oxazepam Glucuronidation: Cannabinoid-Oxazepam Drug Interactions.

Benzodiazepines (BZDs) such as oxazepam are commonly prescribed depressant drugs known for their anxiolytic, hypnotic, muscle relaxant, and anticonvulsant effects and are frequently used in conjunction with other illicit drugs including cannabis. Oxazepam is metabolized in an enantiomeric-specific manner by glucuronidation, with S-oxazepam metabolized primarily by UGT2B15 and R-oxazepam glucuronidation mediated by both UGT 1A9 and 2B7. The goal of the present study was to evaluate the potential inhibitory effects of major cannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), and major THC metabolites, 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (11-COOH-THC), on the UGT-mediated metabolism of R- and S-oxazepam. The cannabinoids and metabolites were screened as inhibitors of R- and S-oxazepam glucuronidation in microsomes isolated from HEK293 cells overexpressing individual UGT enzymes (rUGTs). The IC50 values were determined in human liver microsomes (HLM), human kidney microsomes (HKM), and rUGTs and utilized to estimate the nonspecific, binding-corrected Ki (Ki,u) values and predict the area under the concentration-time curve ratio (AUCR). The estimated Ki,u values observed in HLM for S- and R-oxazepam glucuronidation by CBD, 11-OH-THC, and THC were in the micromolar range (0.82 to 3.7 µM), with the Ki,u values observed for R-oxazepam glucuronidation approximately 2- to 5-fold lower as compared to those observed for S-oxazepam glucuronidation. The mechanistic static modeling predicted a potential clinically significant interaction between oral THC and CBD with oxazepam, with the AUCR values ranging from 1.25 to 3.45. These data suggest a pharmacokinetic drug-drug interaction when major cannabinoids like CBD or THC and oxazepam are concurrently administered.