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Developmental Medicine and Child... Mar 2020To determine: the effectiveness of three anticholinergic medications in reducing drooling in children with developmental disabilities (such as cerebral palsy,...
AIM
To determine: the effectiveness of three anticholinergic medications in reducing drooling in children with developmental disabilities (such as cerebral palsy, intellectual disability, and autism spectrum disorder), the frequency and nature of side effects, and their impact on treatment discontinuation.
METHOD
After prescription of benzhexol hydrochloride, glycopyrrolate, or scopolamine patches at a tertiary saliva control clinic, all carers of 110 consecutive, eligible patients were recruited over a 5-year period. They provided data for 52 weeks, or until drug discontinuation, on compliance, drooling, adverse effects, and reasons for cessation. We evaluated and compared best drooling response, side effects, and drug cessation rates using survival analysis, and the effect of baseline variables on the discontinuation rate using proportional hazards regression.
RESULTS
Among 110 participants (71 males, 39 females; mean age 8y 5mo [SD 4y 3mo], range 1y 11mo-18y 11mo), benzhexol, glycopyrrolate, and scopolamine were prescribed 81, 62, and 17 times respectively, with respective response rates of 85%, 75%, and 65%. Poor head control and poor oromotor function were predictive of poor response. Side effects frequently prompted drug cessation in males more than females (hazard ratio 1.8 [95% confidence interval 1.0-3.2], p=0.048). Glycopyrrolate had the fewest side effects.
INTERPRETATION
Benzhexol, glycopyrrolate, and scopolamine reduce drooling, but improvement is offset by adverse side effects. Overall, glycopyrrolate performs best.
WHAT THIS PAPER ADDS
In drooling, glycopyrrolate produced the greatest improvement with fewer side effects compared with benzhexol and scopolamine. Poor head control and poor oromotor function were associated with poor response. Medication side effects were common and often led to treatment discontinuation. Behavioural issues instigated cessation of benzhexol more often in males than females.
Topics: Adolescent; Child; Child, Preschool; Cholinergic Antagonists; Developmental Disabilities; Female; Glycopyrrolate; Humans; Infant; Male; Scopolamine; Sialorrhea; Treatment Outcome; Trihexyphenidyl
PubMed: 31495925
DOI: 10.1111/dmcn.14350 -
Journal of the American College of... Feb 2002
Topics: Coronary Artery Disease; Humans; Muscarinic Antagonists; Scopolamine
PubMed: 11849885
DOI: No ID Found -
British Medical Journal Oct 1968
Topics: Motion Sickness; Naval Medicine; Scopolamine
PubMed: 5681046
DOI: No ID Found -
The Journal of Pharmacology and... Jun 2021The cholinergic nervous system has been implicated in mood disorders, evident in the fast-onset antidepressant effects of scopolamine, a potent muscarinic antagonist, in...
The cholinergic nervous system has been implicated in mood disorders, evident in the fast-onset antidepressant effects of scopolamine, a potent muscarinic antagonist, in clinical studies. One prominent disadvantage of the use of scopolamine in the treatment of depression is its detrimental effects on cognition, especially as such effects might aggravate cognitive deficits that occur with depression itself. Thus, the identification of antimuscarinic drugs that are free of such detrimental effects may provide an important avenue for the development of novel therapeutics for the management of depression. The present data in rats indicate that a historical muscarinic antagonist, L-687,306, and a muscarinic antagonist of our own design, CJ2100, were as or more effective than scopolamine in antagonizing both the bradycardic effects of the muscarinic agonist arecoline in cardiovascular studies and its discriminative stimulus and rate-decreasing effects in behavioral studies. Additionally, both novel muscarinic antagonists were as effective as scopolamine in decreasing immobility in the forced swim test, a preclinical indicator of potential antidepressant activity. However, at equieffective or even larger doses, they were considerably less disruptive than scopolamine in assays of cognition-related behavior. All three drugs displayed high specificity for the mAChRs with few off-target binding sites, and CJ2100 showed modest affinity across the mAChRs when compared with L-687,306 and scopolamine. These data emphasize the dissimilar pharmacological profiles that are evident across antimuscarinic compounds and the potential utility of novel antagonists for the improved treatment of depression. SIGNIFICANCE STATEMENT: Some clinical studies with the muscarinic antagonist scopolamine document its ability to produce antidepressant effects in patients with mood disorders; however, scopolamine also has well known adverse effects on both autonomic and centrally mediated physiological functions that limit its therapeutic use. This study characterizes the cardiovascular and discriminative stimulus effects of two novel muscarinic antagonists, L-687,306 and CJ2100, that produce antidepressant-like effects in a rodent model (forced swim test) without affecting touchscreen-based cognitive performance (titrating psychomotor vigilance and delayed matching-to-position).
Topics: Cognition; Muscarinic Antagonists; Scopolamine
PubMed: 33712507
DOI: 10.1124/jpet.120.000337 -
Food Chemistry Nov 2022A high throught methododology based on a green extraction technique, µSPEed®, followed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)...
A high throught methododology based on a green extraction technique, µSPEed®, followed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) has been proposed for the analysis of atropine and scopolamine in tea and herbal tea infusions. For this, a digiVOL® Digital Syringe was used with different sorbents and working conditions to obtain a fast and efficient µSPEed® extraction. The best performance was achieved with a PS/DVB sorbent phase, sample loading of 5 × 500 µL and elution with 2 × 100 µL aliquots of methanol. The strategy based on µSPEed® followed by HPLC-MS/MS was validated, attaining quantitation limits lower than 0.15 ng mL and recoveries between 94 and 106% for both analytes and applied to seventeen tea and herbal tea infusions. Fourteen infusions showed contamination with one or both analytes above the maximum content legislated (sum of atropine and scopolamine < 0.2 ng mL).
Topics: Atropine; Chromatography, High Pressure Liquid; Limit of Detection; Scopolamine; Tandem Mass Spectrometry; Tea; Teas, Herbal
PubMed: 35728464
DOI: 10.1016/j.foodchem.2022.133512 -
The Cochrane Database of Systematic... Jul 2007Motion sickness - the discomfort experienced when perceived motion disturbs the organs of balance - may include symptoms such as nausea, vomiting, pallor, cold sweats,... (Review)
Review
BACKGROUND
Motion sickness - the discomfort experienced when perceived motion disturbs the organs of balance - may include symptoms such as nausea, vomiting, pallor, cold sweats, hypersalivation, hyperventilation and headaches. The control and prevention of these symptoms have included pharmacological, behavioural and complementary therapies. Although scopolamine (hyoscine) has been used in the treatment and prevention of motion sickness for decades, there have been no systematic reviews of its effectiveness.
OBJECTIVES
To assess the effectiveness of scopolamine versus no therapy, placebo, other drugs, behavioural and complementary therapy or two or more of the above therapies in combination for motion sickness in persons (both adults and children) without known vestibular, visual or central nervous system pathology.
SEARCH STRATEGY
The Cochrane Ear, Nose and Throat Disorders Group Specialised Register, the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2007), MEDLINE (OVID, 1966 to May 2007), EMBASE (1974 to May 2007) CINAHL (OVID, 1982 to May 2007) and reference lists of retrieved studies were searched for relevant studies. No language restrictions were applied. The date of the last search was May 2007.
SELECTION CRITERIA
All parallel-arm, randomised controlled trials (RCTs) focusing on scopolamine versus no therapy, placebo, other drugs, behavioural and complementary therapy or two or more of the above therapies in combination were included. Outcomes relating to the prevention of onset or treatment of clinically-defined motion sickness, task ability and psychological tests, changes in physiological parameters and adverse effects were considered.
DATA COLLECTION AND ANALYSIS
Data from the studies were extracted independently by two authors using standardised forms. Study quality was assessed. Dichotomous data were expressed as odds ratio (OR) and a pooled OR was calculated using the random-effects model.
MAIN RESULTS
Of 35 studies considered potentially relevant, 14 studies enrolling 1025 subjects met the entry criteria. Scopolamine was administered via transdermal patches, tablets or capsules, oral solutions or intravenously. Scopolamine was compared against placebo, calcium channel antagonists, antihistamine, methscopolamine or a combination of scopolamine and ephedrine. Studies were generally small in size and of varying quality. Scopolamine was more effective than placebo in the prevention of symptoms. Comparisons between scopolamine and other agents were few and suggested that scopolamine was superior (versus methscopolamine) or equivalent (versus antihistamines) as a preventative agent. Evidence comparing scopolamine to cinnarizine or combinations of scopolamine and ephedrine is equivocal or minimal. Although sample sizes were small, scopolamine was no more likely to induce drowsiness, blurring of vision or dizziness compared to other agents. Dry mouth was more likely with scopolamine than with methscopolamine or cinnarizine. No studies were available relating to the therapeutic effectiveness of scopolamine in the management of established symptoms of motion sickness.
AUTHORS' CONCLUSIONS
The use of scopolamine versus placebo in preventing motion sickness has been shown to be effective. No conclusions can be made on the comparative effectiveness of scopolamine and other agents such as antihistamines and calcium channel antagonists. In addition, no randomised controlled trials were identified that examined the effectiveness of scopolamine in the treatment of established symptoms of motion sickness.
Topics: Adult; Child; Humans; Motion Sickness; Muscarinic Antagonists; Randomized Controlled Trials as Topic; Scopolamine; Treatment Outcome
PubMed: 17636710
DOI: 10.1002/14651858.CD002851.pub3 -
Toxins May 2023Atropine and scopolamine belong to the tropane alkaloid (TA) family of natural toxins. They can contaminate teas and herbal teas and appear in infusions. Therefore, this...
Atropine and scopolamine belong to the tropane alkaloid (TA) family of natural toxins. They can contaminate teas and herbal teas and appear in infusions. Therefore, this study focused on analyzing atropine and scopolamine in 33 samples of tea and herbal tea infusions purchased in Spain and Portugal to determine the presence of these compounds in infusions brewed at 97 °C for 5 min. A rapid microextraction technique (µSPEed) followed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to analyze the selected TAs. The results showed that 64% of the analyzed samples were contaminated by one or both toxins. White and green teas were generally more contaminated than black and other herbal teas. Of the 21 contaminated samples, 15 had concentrations above the maximum limit for liquid herbal infusions (0.2 ng/mL) set by Commission Regulation (EU) 2021/1408. In addition, the effects of heating conditions (time and temperature) on atropine and scopolamine standards and naturally contaminated samples of white, green, and black teas were evaluated. The results showed that at the concentrations studied (0.2 and 4 ng/mL), there was no degradation in the standard solutions. Brewing with boiling water (decoction) for 5 and 10 min allowed for higher extraction of TAs from dry tea to infusion water.
Topics: Atropine; Scopolamine; Teas, Herbal; Tandem Mass Spectrometry; Temperature; Tropanes; Tea; Water
PubMed: 37368663
DOI: 10.3390/toxins15060362 -
Toxins Apr 2022This study investigated the effects of wasp venom (WV) from the yellow-legged hornet, , on scopolamine (SCO)-induced memory deficits in mice, as well as the antioxidant...
This study investigated the effects of wasp venom (WV) from the yellow-legged hornet, , 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 -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.
Topics: Animals; Antioxidants; Bee Venoms; Memory Disorders; Mice; NF-E2-Related Factor 2; Oxidative Stress; Scopolamine; Wasp Venoms
PubMed: 35448865
DOI: 10.3390/toxins14040256 -
Molecules (Basel, Switzerland) Sep 2021A fast method for the determination of tropane alkaloids, using a portable CE instrument with a capacitively coupled contactless conductivity detector (CE-CD) was...
A fast method for the determination of tropane alkaloids, using a portable CE instrument with a capacitively coupled contactless conductivity detector (CE-CD) was developed and validated for determination of atropine and scopolamine in seeds from family plants. Separation was obtained within 5 min, using an optimized background electrolyte consisting of 0.5 M acetic acid with 0.25% () β-CD. The limit of detection and quantification was 0.5 µg/mL and 1.5 µg/mL, respectively, for both atropine and scopolamine. The developed method was validated with the following parameters-precision (CV): 1.07-2.08%, accuracy of the assay (recovery, RE): 101.0-102.7% and matrix effect (ME): 92.99-94.23%. Moreover, the optimized CE-CD method was applied to the analysis of plant extracts and pharmaceuticals, proving its applicability and accuracy.
Topics: Atropine; Electrophoresis, Capillary; Limit of Detection; Scopolamine; Solanaceae; Solanaceous Alkaloids
PubMed: 34641293
DOI: 10.3390/molecules26195749 -
The New Phytologist Mar 2020Some medicinal plants of the Solanaceae produce pharmaceutical tropane alkaloids (TAs), such as hyoscyamine and scopolamine. Littorine is a key biosynthetic intermediate...
Some medicinal plants of the Solanaceae produce pharmaceutical tropane alkaloids (TAs), such as hyoscyamine and scopolamine. Littorine is a key biosynthetic intermediate in the hyoscyamine and scopolamine biosynthetic pathways. However, the mechanism underlying littorine formation from the precursors phenyllactate and tropine is not completely understood. Here, we report the elucidation of littorine biosynthesis through a functional genomics approach and functional identification of two novel biosynthesis genes that encode phenyllactate UDP-glycosyltransferase (UGT1) and littorine synthase (LS). UGT1 and LS are highly and specifically expressed in Atropa belladonna secondary roots. Suppression of either UGT1 or LS disrupted the biosynthesis of littorine and its TA derivatives (hyoscyamine and scopolamine). Purified His-tagged UGT1 catalysed phenyllactate glycosylation to form phenyllactylglucose. UGT1 and LS co-expression in tobacco leaves led to littorine synthesis if tropine and phenyllactate were added. This identification of UGT1 and LS provides the missing link in littorine biosynthesis. The results pave the way for producing hyoscyamine and scopolamine for medical use by metabolic engineering or synthetic biology.
Topics: Atropine Derivatives; Genomics; Scopolamine; Solanaceae; Tropanes
PubMed: 31705812
DOI: 10.1111/nph.16317