Synergistic neuroprotection by phytocompounds of Bacopa monnieri in scopolamine-induced Alzheimer's disease mice model.

BACKGROUND: Millions of people around the globe are affected by Alzheimer's disease (AD). This crippling condition has no treatment despite intensive studies. Some phytocompounds have been shown to protect against Alzheimer's in recent studies. METHODS: Thus, this work aimed to examine Bacopa monnieri phytocompounds' synergistic effects on neurodegeneration, antioxidant activity, and cognition in the scopolamine-induced AD mice model. The toxicity study of two phytocompounds: quercetin and bacopaside X revealed an LD50 of more than 2000 mg/kg since no deaths occurred. RESULTS: The neuroprotection experiment consists of 6 groups i.e., control (saline), scopolamine (1 mg/kg), donepezil (5 mg/kg), Q (25 mg/kg), BX (20 mg/kg), and Q + BX (25 mg/kg + 20 mg/kg). Visual behavioral assessment using the Morris water maze showed that animals in the diseased model group (scopolamine) moved more slowly toward the platform and exhibited greater thigmotaxis behavior than the treatment and control groups. Likewise, the concentration of biochemical NO, GSH, and MDA improved in treatment groups concerning the diseased group. mRNA levels of different marker genes including ChAT, IL-1α, IL-1 ß, TNF α, tau, and ß secretase (BACE1) improved in treatment groups with respect to the disease group. CONCLUSION: Both bacopaside X and quercetin synergistically have shown promising results in neuroprotection. Therefore, it is suggested that Q and BX may work synergistically due to their antioxidant and neuroprotective property.

Ultrasonographic Assessment of Small Intestinal Motility Following Hyoscine Butylbromide Administration in Horses: A Pilot Study.

Horses commonly receive hyoscine butylbromide (HB) prior to hospital admission for colic. This could alter the appearance of the small intestine (SI) on ultrasound scan and affect clinical decision making. The aim of this study was to assess the impact of HB on ultrasonographically assessed SI motility and heart rate. Six horses hospitalised for medical colic with no significant abnormalities on baseline abdominal ultrasound examination were included. Ultrasound was performed in three locations (right inguinal, left inguinal and hepatoduodenal window) before and at 1, 5, 15, 30, 45, 60, 90, and 120 minutes after intravenous injection of 0.3 mg/kg HB. Three blinded reviewers assessed SI motility using a subjective grading scale from 1 to 4, one being normal motility and four being no motility. Moderate interindividual and interobserver variability was observed, but none of the included horses developed dilated turgid loops of SI. Hyoscine butylbromide did not significantly reduce SI motility grade in any location (P = .60 left inguinal, P = .16 right inguinal, P = .09 duodenum). Heart rate (mean ± SD) was 33 ± 3 prior to HB injection and peaked at 71.3 ± 9 one-minute postinjection. Heart rate was significantly increased until 45 minutes (48 ± 9) after HB administration (P = .04). The appearance of dilated turgid SI loops common with strangulating intestinal lesions did not appear to develop following HB administration. Hyoscine butylbromide administered shortly before abdominal ultrasound examination would not be expected to affect clinical decision making in horses without small intestinal disease.

Anticholinergic Versus Antihistaminic Treatment for Simulator Sickness Prevention.

Flight simulators have an essential role in aircrew training. Occasionally, symptoms of motion sickness, defined as simulator sickness, develop during these sessions. Preventive methods for motion sickness have been investigated thoroughly; however, only a few studies have examined preventive treatments for simulator sickness. The aim of this study was to examine the efficacy of scopolamine (an anticholinergic drug) compared with cinnarizine (an antihistaminic drug) for helicopter simulator sickness prevention. A validated simulator sickness questionnaire (SSQ) score was used to determine the severity of simulator sickness symptoms in this study. Preliminary SSQ scores and SSQ scores after each sortie were calculated. Each participant was given scopolamine, cinnarizine, or a placebo in a double-blind randomized manner before the first sortie of each training day. Forty-one helicopter pilots participated in the trial. The average age was 30.5 ± 7.1 years. SSQ values significantly improved from an average of 73.30 in the preliminary SSQ questionnaire to an average of 30.92 after 2 hours following the administration of cinnarizine (P = .012, 95%CI 8.071-76.703). Scopolamine was found to be less effective than both cinnarizine and the placebo in the alleviation of simulator sickness symptoms. This study is the first to compare scopolamine with cinnarizine for simulator sickness prevention. Based on the results of this study, we recommend the use of cinnarizine over scopolamine for simulator sickness prevention.

The Vestibular Time Constant and Clinical Response to Antimotion Sickness Medication.

OBJECTIVE: The therapeutic effects of antimotion sickness medications involve suppression of several components along the vestibular system. Scopolamine-based medications have proved to be the most effective anti-seasickness agents. However, there is high variability in individual responses. The vestibular nuclei, in which the vestibular time constant is modulated, contain acetylcholine receptors which are affected by scopolamine. The hypothesis of the study was that successful seasickness prevention by scopolamine requires vestibular suppression to be reflected by the shortening of the vestibular time constant. DESIGN: Subjects were 30 naval crew members suffering from severe seasickness and were treated with oral scopolamine. The study participants were defined as responsive or non-responsive to the anti-seasickness medication according to the clinical outcome: successful response to scopolamine was defined as a reduction of seasickness severity from the highest score of 7 according to the Wiker scale to 4 or less. Scopolamine and placebo were assigned to each subject in a crossover, double-blind design. The horizontal semicircular canal time constant was evaluated by a computerized rotatory chair before, 1 and 2 hours after drug or placebo administration. RESULTS: The vestibular time constant was significantly shortened from 16.01 ± 3.43 seconds to 12.55 ± 2.40 seconds ( p < 0.001) in the scopolamine-responsive group but not in the nonresponsive group. In contrast, vestibular time constant values were 13.73 ± 4.08 and 12.89 ± 4.48 for baseline and 2 hours measurements, respectively. This change was not statistically significant. CONCLUSIONS: Reduction in the vestibular time constant after scopolamine administration can be used to predict whether motion sickness alleviation will occur. This will enable the administration of appropriate pharmaceutical treatment without the need for prior exposure to sea conditions.

Hanna Rion and The Weekly Dispatch's twilight sleep crusade.

The story of twilight sleep is an important, yet neglected, episode in the history of obstetric pain relief in Britain. One reason for its neglect in historical writing is that most of the discussion of the therapy took place in newspapers, particularly the Weekly Dispatch Using digitised newspapers, as well as medical journals, this article reconstructs the largely overlooked story of twilight sleep in Britain. Twilight sleep was comprised of two drugs, scopolamine and morphine, which acted together to remove the pain of labour, as well as memory of it. Twilight sleep gained popularity in 1915 in Britain, a year after it became popular in America, on which most scholarship has focused. One of the main advocates for the use of twilight sleep in Britain was Hanna Rion, who wrote a series of weekly articles in 1916 campaigning for its use. Rion's articles, and the response to them, show how the rise in popularity of twilight sleep reflected concerns about a declining birth rate amidst the backdrop of World War I. Through studying twilight sleep we see how women began to see themselves as consumers and shape medical practice, before the natural childbirth movement, which it has traditionally been attributed to. Therefore, twilight sleep provides us with the missing link in the story of obstetric anaesthetics, between the discovery of chloroform in 1847 and the natural childbirth movement in the 1930s.

Design, Synthesis, and Pharmacological Evaluation of Embelin-Aryl/alkyl Amine Hybrids as Orally Bioavailable Blood-Brain Barrier Permeable Multitargeted Agents with Therapeutic Potential in Alzheimer's Disease: Discovery of SB-1448.

The complex and multifaceted nature of Alzheimer's disease has brought about a pressing demand to develop ligands targeting multiple pathways to combat its outrageous prevalence. Embelin is a major secondary metabolite of Embelia ribes Burm f., one of the oldest herbs in Indian traditional medicine. It is a micromolar inhibitor of cholinesterases (ChEs) and ß-site amyloid precursor protein cleaving enzyme 1 (BACE-1) with poor absorption, distribution, metabolism, and excretion (ADME) properties. Herein, we synthesize a series of embelin-aryl/alkyl amine hybrids to improve its physicochemical properties and therapeutic potency against targeted enzymes. The most active derivative, 9j (SB-1448), inhibits human acetylcholinesterase (hAChE), human butyrylcholinesterase (hBChE), and human BACE-1 (hBACE-1) with IC50 values of 0.15, 1.6, and 0.6 µM, respectively. It inhibits both ChEs noncompetitively with ki values of 0.21 and 1.3 µM, respectively. It is orally bioavailable, crosses blood-brain barrier (BBB), inhibits Aß self-aggregation, possesses good ADME properties, and protects neuronal cells from scopolamine-induced cell death. The oral administration of 9j at 30 mg/kg attenuates the scopolamine-induced cognitive impairments in C57BL/6J mice.

Polyphenols from Conyza dioscoridis (L.) ameliorate Alzheimer's disease- like alterations through multi-targeting activities in two animal models.

BACKGROUND: Recent investigations suggested that anticancer agents may inhibit the progression of Alzheimer's disease (AD) pathology. Conyza dioscoridis (L.) was demonstrated to have anticancer, antioxidant, anti-inflammatory and antidiabetic effects. This study was carried out to investigate the efficacy of polyphenols from Conyza dioscoridis (L.) extract (PCDE) on AD. METHODS: Impacts of 3 doses of PCDE and donepezil, a reference drug, on the features of Alzheimer's disease in two animal models were investigated. RESULTS: PCDE ameliorated the memory and learning impairment shown in rats following a single dose of scopolamine (scopolamine model) or 17 weeks of high-fat/high-fructose(HF/Hfr) diet coupled with a single dose of streptozotocin, (25 mg/kg) (T2D model). They reduced significantly the high hippocampal cholinesterase activity in the two models of rats. Administration of PCDE for 8 weeks in the T2D model showed a significant reduction in hippocampal GSK-3ß, caspase-3 activity and increase in the inhibited glutamate receptor expression (AMPA GluR1 subunit and NMDA receptor subunits NR1, NR2A, NR2B). A significant reduction of HOMA-insulin resistance and serum hypercholesterolemia was observed. The Tau hyperphosphorylation and Aß 1-42 generation in the hippocampal of T2D rats were significantly decreased by PCDE. Modulation of the oxidative stress markers, (rise in GH and SOD; decrease in MDA levels) and a significant reduction of TNF-α and IL-1ß in the hippocampus of T2D rats treated by PCDE extract were important findings in this study. The highest dose tested was 4% of the highest safe dose. CONCLUSION: Our study suggests that PCDE is multi-targeting agent with multiple beneficial activities in combating features of AD. This study may provide a novel therapeutic strategy for AD treatment that warrants clinical studies.

Insights of Valacyclovir in Treatment of Alzheimer's Disease: Computational Docking Studies and Scopolamine Rat Model.

BACKGROUND: Alzheimer's Disease (AD) impairs memory and cognitive functions in the geriatric population and is characterized by intracellular deposition of neurofibrillary tangles, extracellular deposition of amyloid plaques, and neuronal degeneration. Literature suggests that latent viral infections in the brain act as prions and promote neurodegeneration. Memantine possesses both anti-viral and N-methyl-D-aspartate (NMDA) receptor antagonistic activity. OBJECTIVES: This research was designed to evaluate the efficacy of antiviral agents, especially valacyclovir, a prodrug of acyclovir in ameliorating the pathology of AD based on the presumption that anti-viral agents targeting the Herpes Simplex Virus (HSV) can have a protective effect on neurodegenerative diseases like Alzheimer's disease. METHODS: Thus, we evaluated acyclovir's potential activity by in-silico computational docking studies against acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and beta-secretase 1 (BACE-1). These findings were further evaluated by in-vivo scopolamine-induced cognitive impairment in rats. Two doses of valacyclovir, a prodrug of acyclovir (100 mg/kg and 150 mg/kg orally) were tested. RESULTS: Genetic Optimisation for Ligand Docking scores and fitness scores of acyclovir were comparable to donepezil. Valacyclovir improved neurobehavioral markers. It inhibited AChE and BuChE (p<0.001) enzymes. It also possessed disease-modifying efficacy as it decreased the levels of BACE-1 (p<0.001), amyloid beta 1-42 (p<0.001), amyloid beta 1-40 (p<0.001), phosphorylatedtau (p<0.001), neprilysin (p<0.01), and insulin-degrading enzyme. It ameliorated neuroinflammation through decreased levels of tumour necrosis factor α (p<0.001), nuclear factor-kappa B (p<0.001), interleukin 6 (p<0.001), interleukin 1 beta (p<0.001), and interferon-gamma (p<0.001). It also maintained synaptic plasticity and consolidated memory. Histopathology showed that valacyclovir could restore cellular density and also preserve the dentate gyrus. CONCLUSION: Valacyclovir showed comparable activity to donepezil and thus can be further researched for the treatment of Alzheimer's disease.

A Randomized Controlled Trial of Intravenous Scopolamine Versus Active-Placebo Glycopyrrolate in Patients With Major Depressive Disorder.

Objective: To investigate scopolamine's rapid-acting antidepressant effects using an active placebo comparator. Most prior intravenous scopolamine studies reduced depressive symptomatologies compared to saline placebo infusions within 3 days. However, the confounding effect of placebo is unknown given that only saline placebo has been used in prior studies.Methods: In this trial, 40 patients with major depressive disorder were randomized to receive single intravenous doses of either scopolamine hydrobromide (4-6 µg/kg) or glycopyrronium bromide (4 µg/kg) between August 2019 and April 2021 in Auckland, New Zealand. Glycopyrronium was chosen as the active placebo due to its similar antimuscarinic properties to scopolamine but inability to cross the blood-brain barrier. The primary mood outcome measure was the Montgomery-Åsberg Depression Rating Scale (MADRS) administered pre-infusion and 1, 3, 7, 14, 28, and 42 days post-infusion.Results: Per protocol, this trial was abandoned for futility at n = 40. While scopolamine reduced MADRS scores by 12.6 (± 8.7 SD) points at day 3, glycopyrronium showed similar reductions (11.2 ± 9.6 SD). Frequentist linear mixed models showed no antidepressant effects of scopolamine versus placebo (d = 0.17), and Bayesian mixed effect models showed moderate evidence in favor of the null hypothesis at day 3 (Bayes factor = 0.32). Participants remained well-blinded to drug allocation, with 50% of participants correctly guessing their allocation.Conclusions: The observed MADRS improvement was larger than in prior studies, but no antidepressant effects were observed. This study using an active placebo confirms recent studies demonstrating the lack of antidepressant efficacy of scopolamine.Trial Registration: Australian New Zealand Clinical Trials Registry identifier: ACTRN12619000569101.

[Treatment options for drug-induced sialorrhea: Prescribing guidelines]. / Prise en charge de l'hypersialorrhée iatrogène : revue de la littérature et recommandations pratiques.

OBJECTIVES: Drug-induced hypersalivation is a frequent drug adverse event of psychotropic drugs. This excess salivary pooling in the mouth can cause an impairment of a patient's quality of life leading to low rates of medication adherence. The optimal management of hypersalivation is thus crucial to improve patient care. To date, no recommendations for limiting drug-induced hypersalivation have been published. In this study, we conducted a systematic review to investigate the effectiveness of interventions aimed at reducing drug-induced hypersalivation. METHODS: Treatment of drug-induced sialorrhea based on case reports and clinical studies were sought in May 2021 from PubMed, Google Scholar and Science Direct (keywords : « treatment ¼, « hypersalivation ¼, « induced ¼, « drug ¼, « clozapine ¼). Articles published between 1966 to May 2021 on the treatment of drug-induced hypersalivation were included in this study. RESULTS: Sixty-seven articles were selected in this narrative review. First, patient education associated with non-drug related management are essential to improve the compliance to drugs inducing hypersalivation. The non-drug related management should be initiated with an increase in the frequency of swallowing with chewing gum. In the case of ineffectiveness, the dosage of drug responsive of sialorrhea can be adjusted according to the patient's response and his/her medical history (i.e. reducing the dose or splitting the daily dose). Finally, if the problem persists, a symptomatic treatment can be added according to the type of sialorrhea (diurnal or nocturnal), preferred galenic by patient, tolerance and availability of drugs. Several drugs have been tested to reduce hypersalivation induced by clozapine (61/67), risperidone (3/67), quetiapine (2/67) and aripiprazole (2/67). Among the 63 articles targeting a specific corrective treatment, anticholinergic agents were most described in the literature (41 cases out of 63) with atropine, glycopyrrolate and scopolamine (6/41 each). Other agents were described as clinically effective on hypersalivation: dopamine antagonists (9/63) with amisulpride (5/9), alpha-2-adrenergic agonists (5/63) with clonidine (3/5), botulinic toxin (4/63), and terazosine, moclobemide, bupropion and N-acetylcysteine (for each 1/63). CONCLUSIONS: In the case of drug-induced hypersalivation, after failure of non-drug therapies and dosage optimization of the causative treatment, an anticholinergic drug can be initiated. In case of insufficient response, the different treatments presented can be used depending on the galenic form, tolerance and access to those medications. The assessment of the risk-benefit balance should be systematic. The heterogeneity of the studies, the little knowledge about the pharmacological mechanism of saliva flow modulation and the unavailability of corrective drugs are different factors contributing to the complexity of therapeutic optimization.

Where do we go next in antidepressant drug discovery? A new generation of antidepressants: a pivotal role of AMPA receptor potentiation and mGlu2/3 receptor antagonism.

INTRODUCTION: Major depressive disorder remains a prevalent world-wide health problem. Currently available antidepressant medications take weeks of dosing, do not produce antidepressant response in all patients, and have undesirable ancillary effects. AREAS COVERED: The present opinion piece focuses on the major inroads to the creation of new antidepressants. These include N-methyl-D-aspartate (NMDA) receptor antagonists and related compounds like ketamine, psychedelic drugs like psilocybin, and muscarinic receptor antagonists like scopolamine. The preclinical and clinical pharmacological profile of these new-age antidepressant drugs is discussed. EXPERT OPINION: Preclinical and clinical data have accumulated to predict a next generation of antidepressant medicines. In contrast to the current standard of care antidepressant drugs, these compounds differ in that they demonstrate rapid activity, often after a single dose, and effects that outlive their presence in brain. These compounds also can provide efficacy for treatment-resistant depressed patients. The mechanism of action of these compounds suggests a strong glutamatergic component that involves the facilitation of AMPA receptor function. Antagonism of mGlu2/3 receptors is also relevant to the antidepressant pharmacology of this new class of drugs. Based upon the ongoing efforts to develop these new-age antidepressants, new drug approvals are predicted in the near future.

5-HT5A Receptor Antagonist ASP5736 Ameliorates Several Abnormal Behaviors in an Fmr1-Targeted Transgenic Male Rat Model of Fragile X Syndrome.

BACKGROUND: Fragile X syndrome (FXS) is a genetic condition that causes a range of developmental problems, including intellectual disability, aggressive behavior, anxiety, abnormal sensory processing, and cognitive impairment. Despite intensive preclinical research in Fmr1-targeted transgenic mice, an effective treatment for FXS has yet to be developed. We previously demonstrated that ASP5736, a 5-Hydroxytryptamine (serotonin) receptor 5A receptor antagonist, ameliorated scopolamine-induced working memory deficits in mice, reference memory impairment in aged rats, and methamphetamine-induced positive symptoms and phencyclidine-induced cognitive impairment in animal models of schizophrenia. We hypothesized that ASP5736 may be effective for ameliorating similar behavior deficits in male Fmr1-targeted transgenic rats as a preclinical model of FXS. METHODS: We evaluated the effect of acute oral administration of ASP5736 on the abnormal behavior of hyperactivity (0.01, 0.1 mg/kg), prepulse inhibition (0.01, 0.03, 0.1 mg/kg), and the novel object recognition task (0.1 mg/kg) in Frmr1-knockout (KO) rats. RESULTS: Fmr1-KO rats showed body weight gain, hyperactivity, abnormal sensory motor gating, and cognitive impairment. ASP5736 (0.1 mg/kg) reversed the hyperactivity and ameliorated the sensory motor gating deficits (0.03-0.1 mg/kg). ASP5736 (0.01 mg/kg) also improved cognitive impairment. CONCLUSIONS: ASP5736 is a potential drug candidate for FXS. Further studies are needed to confirm its clinical efficacy.

Wasp Venom Ameliorates Scopolamine-Induced Learning and Memory Impairment in Mice.

This study investigated the effects of wasp venom (WV) from the yellow-legged hornet, Vespa velutina, on scopolamine (SCO)-induced memory deficits in mice, as well as the antioxidant activity in HT22 murine hippocampal neuronal cells in parallel comparison with bee venom (BV). The WV was collected from the venom sac, freeze-dried. Both venoms exhibited free radical scavenging capabilities in a concentration-dependent manner. In addition, the venom treatment enhanced cell viability at the concentrations of ≤40 µg/mL of WV and ≤4 µg/mL of BV in glutamate-treated HT22 cells, and increased the transcriptional activity of the antioxidant response element (ARE), a cis-acting enhancer which regulates the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)-downstream antioxidant enzymes. Concurrently, WV at 20 µg/mL significantly increased the expression of a key antioxidant enzyme heme oxygenase 1 (HO-1) in HT22 cells despite no significant changes observed in the nuclear level of Nrf2. Furthermore, the intraperitoneal administration of WV to SCO-treated mice at doses ranged from 250 to 500 µg/kg body weight ameliorated memory impairment behavior, reduced histological injury in the hippocampal region, and reduced oxidative stress biomarkers in the brain and blood of SCO-treated mice. Our findings demonstrate that WV possess the potential to improve learning and memory deficit in vivo while further study is needed for the proper dose and safety measures and clinical effectiveness.

Effect of intravenous scopolamine before stapling, on postoperative nausea and vomiting in sleeve gastrectomy patients: a randomized controlled trial.

INTRODUCTION: Postoperative nausea and vomiting (PONV) is a common complication of general anesthesia that is further potentiated in an obese patient undergoing a bariatric procedure. Literature shows trials of myriad of drugs used alone or in combination, as a prophylaxis for this cohort of patients with varied benefits. OBJECTIVE: The objective of the study was to determine the effect of intravenous scopolamine prior to stapling in obese patients undergoing sleeve gastrectomy. METHODOLOGY: A prospective randomized controlled trial of consecutive patients with BMI > 35 kg/m2, undergoing laparoscopic sleeve gastrectomy (LSG) was performed after approval of the hospital's ethical committee, explanation of trial to the patients and obtaining a consent. Patients were randomized into two groups; patients receiving intravenous scopolamine just before firing first stapler (Group 1) and patients receiving placebo (Group 2). Primary outcome parameter was PONV. The secondary outcome parameters were use of rescue antiemetic and time to oral intake. RESULTS: In our study, out of 100 cases of patients undergoing LSG, 50 received scopolamine before stapling and 50 were assigned to the control group. There was no significant difference between the two groups in terms of PONV. The group receiving scopolamine had lesser use of rescue antiemetic but no difference in time to oral intake. CONCLUSION: We concluded that incidence of PONV in obese patients undergoing LSG is not affected by scopolamine. Further trials are needed to validate the results.

Prophylactic scopolamine butylbromide reduced death rattle in patients in the dying phase.

SOURCE CITATION: van Esch HJ, van Zuylen L, Geijteman ECT, et al. Effect of prophylactic subcutaneous scopolamine butylbromide on death rattle in patients at the end of life: the SILENCE randomized clinical trial. JAMA. 2021;326:1268-76. 34609452.

Hyoscine butylbromide in pain reduction associated with ultrasound-guided manual vacuum aspiration: a randomized placebo-controlled trial.

RESEARCH QUESTION: What is the effect of adding an anti-spasmodic drug to an existing ultrasound-guided manual vacuum aspiration (USG-MVA) protocol to alleviate immediate post-procedure abdominal cramping pain in women treated for early pregnancy loss? DESIGN: Double-blind, placebo-controlled, randomized controlled trial conducted between February 2018 and January 2020. Participants were assigned to receive a 1-ml intravenous injection containing 20-mg hyoscine butylbromide (HBB) (n=55) or saline (n =56) as a control immediately before USG-MVA. Primary outcome was reduced abdominal pain after adding a 20-mg dose of HBB to the current pain control regimen. Secondary outcomes were vaginal pain, complications and side-effects, women's pre- and post-procedure psychological state, physiological stress (saliva alpha-amylase) and procedure pain control satisfaction. Two-way mixed ANOVA was used to evaluate the main effects and interactions. RESULTS: VAS abdominal pain scores in the HBB group were 16% lower immediately after and 21% lower 2 h after surgery (not statistically significant). Two-way ANOVA indicated that time (F[1108] = 83.41, P < 0.001) was the only significant main effect for reduced abdominal pain after the procedure and vaginal pain score (F[1108] = 180.1, P < 0.0001) but not drug received. No adverse events were reported. No significant difference was found for psychological state, physiological stress and procedure pain control satisfaction between the two groups. CONCLUSIONS: Anti-spasmodic drugs can help to reduce abdominal cramping pain associated with USG-MVA; HBB produced an insignificant decrease in abdominal pain score. Further studies with longer acting or larger doses of anti-spasmodic drugs are warranted.

Scopolamine prevents aberrant mossy fiber sprouting and facilitates remission of epilepsy after brain injury.

Prevention or modification of acquired epilepsy in patients at risk is an urgent, yet unmet, clinical need. Following acute brain insults, there is an increased risk of mesial temporal lobe epilepsy (mTLE), which is often associated with debilitating comorbidities and reduced life expectancy. The latent period between brain injury and the onset of epilepsy may offer a therapeutic window for interfering with epileptogenesis. The pilocarpine model of mTLE is widely used in the search for novel antiepileptogenic treatments. Recent biochemical studies indicated that cholinergic mechanisms play a role in the epileptogenic alterations induced by status epilepticus (SE) in this and other models of mTLE, which prompted us to evaluate whether treatment with the muscarinic antagonist scopolamine during the latent period after SE is capable of preventing or modifying epilepsy and associated behavioral and cognitive alterations in female Sprague-Dawley rats. First, in silico pharmacokinetic modeling was used to select a dosing protocol by which M-receptor inhibitory brain levels of scopolamine are maintained during prolonged treatment. This protocol was verified by drug analysis in vivo. Rats were then treated twice daily with scopolamine over 17 days after SE, followed by drug wash-out and behavioral and video/EEG monitoring up to ~6 months after SE. Compared to vehicle controls, rats that were treated with scopolamine during the latent period exhibited a significantly lower incidence of spontaneous recurrent seizures during periods of intermittent recording in the chronic phase of epilepsy, less behavioral excitability, less cognitive impairment, and significantly reduced aberrant mossy fiber sprouting in the hippocampus. The present data may indicate that scopolamine exerts antiepileptogenic/disease-modifying activity in the lithium-pilocarpine rat model, possibly involving increased remission of epilepsy as a new mechanism of disease-modification. For evaluating the rigor of the present data, we envision a study that more thoroughly addresses the gender bias and video-EEG recording limitations of the present study.

Efficacy of scopolamine plus propofol in the treatment of recalcitrant psoriasis: A pilot study.

Accumulating evidence suggests that botulinum neurotoxins (BoNTs), which inhibit acetylcholine release, can be used for treating plaque psoriasis. The therapeutic effects of scopolamine occur through antagonism of central muscarinic acetylcholine receptors. Thus, scopolamine has potential for the treatment of psoriasis. We aimed to evaluate the efficacy and safety of scopolamine plus propofol for the treatment of recalcitrant psoriasis. Twelve patients with recalcitrant psoriasis were enrolled. Patients received intravenous injection of scopolamine plus propofol for 5 consecutive days per month for a total of 3 months. Clinical efficacy was evaluated using a Psoriasis Area and Severity Index (PASI) score. Efficacy outcome was ≥75% reduction in PASI score (PASI75) from baseline. Two patients were lost to follow-up. At week 8, two of 10 patients (20%) achieved PASI75, and at week 12, seven of 10 (70%) achieved PASI75. Treatment was well tolerated, with no reported adverse events. Our study revealed the efficacy and safety of scopolamine plus propofol for the treatment of recalcitrant psoriasis. Scopolamine plus propofol therapy may be a new treatment for recalcitrant psoriasis.

The role of perioperative medications in urinary retention following midurethral sling.

AIMS: Postoperative urinary retention (PUR) is a known complication of midurethral sling (MUS) placement. The use of certain perioperative medications may influence the risk of this complication. This study aimed to investigate the association of perioperative medications with urinary retention after MUS. METHODS: This was a retrospective study of women undergoing MUS placement for stress urinary incontinence by a fellowship-trained urologic surgeon between 2015 and 2018, under approval by the Institutional Review Board. Both retropubic and transobturator approaches were included. All patients underwent an active void trial following surgery. Intraoperative medications given by the anesthesia team were retrospectively noted. The Fisher's exact test was used to compare the association of PUR with categorical variables. RESULTS: A total of 82 patients were included, 17 (21%) of whom failed postoperative void trial due to urinary retention. Of 25 patients receiving perioperative scopolamine, 40% failed the postoperative void trial, compared to 12% of patients not receiving scopolamine (p = .048). Groups were then stratified based on scopolamine use due to the observed independent association with PUR. Subgroup analysis revealed a stronger association of postoperative retention with scopolamine in patients undergoing concomitant prolapse surgery. Notably, retention rate and scopolamine use were similar whether patients underwent sling placement alone or in combination with prolapse surgery. Rate of retention was also higher for retropubic versus transobturator slings (36% vs. 9%; p = .005). CONCLUSIONS: Perioperative scopolamine may be associated with an increased risk of postoperative urinary retention following MUS, especially in the setting of a concomitant prolapse surgery.