A supramolecular atropine sensor was developed, using cucurbit[6]uril as the recognition element. The solid-contact electrode is based on a polymeric membrane incorporating cucurbit[6]uril (CB[6]) as an ionophore, 2-nitrophenyl octyl ether as a solvent mediator, and potassium tetrakis (4-chlorophenyl) borate as an additive. In a MES-NaOH buffer at pH 6, the performance of the atropine sensor is characterized by a slope of (58.7 ± 0.6) mV/dec with a practical detection limit of (6.30 ± 1.62) × 10-7 mol/L and a lower limit of the linear range of (1.52 ± 0.64) × 10-6 mol/L. Selectivity coefficients were determined for different ions and excipients. The obtained results were bolstered by the docking and spectroscopic studies which demonstrated the interaction between atropine and CB[6]. The accuracy of the potentiometric analysis of atropine content in certified reference material was evaluated by the t-Student test. The herein proposed sensor answers the need for reliable methods providing better management of this hospital drug shelf-life while reducing its flush and remediation costs.

Major studies demonstrating the inhibition of myopia in children and juveniles by low-dose atropine eye drops provide little information on the manufacturing process and the exact composition of the atropine dilutions. However, corneal penetration might significantly vary depending on preservatives, such as benzalkonium chloride (BAC), and the atropine concentration. Since there is a trade-off between side effects, stability, and optimal effects of atropine on myopia, it is important to gain better knowledge about intraocular atropine concentrations. We performed an ex vivo study to determine corneal penetration for different formulations. Atropine drops (0.01%) of different formulations were obtained from pharmacies and applied to the cornea of freshly enucleated pig eyes. After 10 min, a sample of aqueous humor was taken and atropine concentrations were determined after liquid-liquid extraction followed by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The variability that originated from variations in applied drop size exceeded the differences between preserved and preservative-free formulations. The atropine concentration in the anterior chamber measured after 10 min was only 3.8 × 10-8 of its concentration in the applied eye drops, corresponding to 502.4 pM. Obviously, the preservative did not facilitate corneal penetration, at least ex vivo. In the aqueous humor of children's eyes, similar concentrations, including higher variability, may be expected in the lower therapeutic window of pharmacodynamic action.

Cycloplegic refraction is mandatory for children to know the eye's refractive status. In this study, we compared cycloplegia induced by cyclopentolate 1% to that induced by atropine 1% by means of retinoscopy.

The conventional dobutamine protocol for the investigation of induced myocardial ischemia is well established. Our objective was to evaluate the effects of early administration of atropine during the dobutamine stress echocardiogram, as compared to its conventional use.

To investigate the change in ocular parameters of anisomyopic children treated with 0.01% atropine.

To examine the changes in choroidal thickness (ChT) after 6 months of 1% or 0.01% atropine treatment and the independent factors associated with eye elongation.

Myopia is an ophthalmic condition affecting more than 1/5th of the world population, especially children. Low-dose atropine eyedrops have been shown to limit myopia evolution during treatment. However, there are currently no commercial industrial forms available and there is little data published concerning the stability of medications prepared by compounding pharmacies. The objective of this study was to evaluate the stability of two 0.1 mg/mL atropine formulations (with and without antimicrobiobial preservatives) for 6 months in two different low-density polyethylene (LDPE) multidose eyedroppers. Analyses used were the following: visual inspection, turbidity, chromaticity measurements, osmolality and pH measurements, atropine quantification by a stability-indicating liquid chromatography method, breakdown product research, and sterility assay. In an in-use study, atropine quantification was also performed on the drops emitted from the multidose eyedroppers. All tested parameters remained stable during the 6 months period, with atropine concentrations above 94.7% of initial concentration. A breakdown product (tropic acid) did increase slowly over time but remained well below usually admitted concentrations. Atropine concentrations remained stable during the in-use study. Both formulations of 0.1 mg/mL of atropine (with and without antimicrobial preservative) were proved to be physicochemically stable for 6 months at 25 °C when stored in LDPE bottles, with an identical microbial shelf-life.

Atropine at a low concentration is considered a safe and effective treatment to mitigate myopia progression. However, the potential unwanted side effects of administering atropine at a low dose on visual functions other than best corrected visual acuity has not been investigated. In this study, we investigate the short-term (12,16, and 20 h) and long-term (1, 2, and 4 weeks) effects of 0.01% atropine (i.e., 0.1 mg/ml) on contrast sensitivity (CS) in patients with myopia.

PurposeRandomized controlled trials have shown the efficacy of atropine for progressive myopia, and this treatment has become the preferred pattern for this condition in Taiwan. This study explores the effectiveness of atropine 0.5% treatment for progressive high myopia and adherence to therapy in a non-Asian country.MethodsAn effectiveness study was performed in Rotterdam, the Netherlands. Overall 77 children (mean age 10.3 years±2.3), of European (n=53), Asian (n=18), and African (n=6) descent with progressive myopia were prescribed atropine 0.5% eye drops daily. Both parents and children filled in a questionnaire regarding adverse events and adherence to therapy. A standardized eye examination including cycloplegic refraction and axial length was performed at baseline and 1, 4, and 12 months after initiation of therapy.ResultsMean spherical equivalent at baseline was -6.6D (±3.3). The majority (60/77, 78%) of children adhered to atropine treatment for 12 months; 11 of the 17 children who discontinued therapy did so within 1 month after the start of therapy. The most prominent reported adverse events were photophobia (72%), followed by reading problems (38%), and headaches (22%). The progression rate of spherical equivalent before treatment (-1.0D/year±0.7) diminished substantially during treatment (-0.1D/year±0.7) compared to those who ceased therapy (-0.5D/year±0.6; P=0.03).ConclusionsDespite the relatively high occurrence of adverse events, our study shows that atropine can be an effective and sustainable treatment for progressive high myopia in Europeans.

Atropine is a clinically relevant anticholinergic drug, which blocks inhibitory effects of the parasympathetic neurotransmitter acetylcholine on heart rate leading to tachycardia. However, many cardiac effects of atropine cannot be adequately explained solely by its antagonism at muscarinic receptors. In isolated mouse ventricular cardiomyocytes expressing a Förster resonance energy transfer (FRET)-based cAMP biosensor, we confirmed that atropine inhibited acetylcholine-induced decreases in cAMP. Unexpectedly, even in the absence of acetylcholine, after G-protein inactivation with pertussis toxin or in myocytes from M2- or M1/3-muscarinic receptor knockout mice, atropine increased cAMP levels that were pre-elevated with the β-adrenergic agonist isoproterenol. Using the FRET approach and in vitro phosphodiesterase (PDE) activity assays, we show that atropine acts as an allosteric PDE type 4 (PDE4) inhibitor. In human atrial myocardium and in both intact wildtype and M2 or M1/3-receptor knockout mouse Langendorff hearts, atropine led to increased contractility and heart rates, respectively. In vivo, the atropine-dependent prolongation of heart rate increase was blunted in PDE4D but not in wildtype or PDE4B knockout mice. We propose that inhibition of PDE4 by atropine accounts, at least in part, for the induction of tachycardia and the arrhythmogenic potency of this drug.

Atropine eye drops are indicated for juvenile myopia progression, cycloplegia, amblyopia, and strabismus. According to the package insert, 10 mg/mL atropine eye drops must be diluted for pediatric patients to prevent systemic adverse effects. Compounding units in hospital pharmaceutical departments or community pharmacies are compelled to prepare this essential medication; however, validated atropine stability data is limited and the shelf life after preparation is extremely short. As it is a long-term treatment, a longer shelf life is necessary to improve patient care. This study aimed to demonstrate the physical, chemical, and microbiological stability of diluted atropine eye drops over a period of six months.

Atropine is an anticholinergic drug which is commonly used in clinical practice. The effect of parasympathetic block with atropine on dynamic cerebrovascular regulation remains unclear. This study was aimed to identify effects of vagolytic atropine on cerebrovascular response during acute orthostatic hypotension in humans.

Scopolamine is a high affinity muscarinic antagonist that is used for the prevention of post-operative nausea and vomiting. 5-HT3 receptor antagonists are used for the same purpose and are structurally related to scopolamine. To examine whether 5-HT3 receptors are affected by scopolamine we examined the effects of this drug on the electrophysiological and ligand binding properties of 5-HT3A receptors expressed in Xenopus oocytes and HEK293 cells, respectively. 5-HT3 receptor-responses were reversibly inhibited by scopolamine with an IC50 of 2.09 μM. Competitive antagonism was shown by Schild plot (pA2 = 5.02) and by competition with the 5-HT3 receptor antagonists [(3)H]granisetron (Ki = 6.76 μM) and G-FL (Ki = 4.90 μM). The related molecule, atropine, similarly inhibited 5-HT evoked responses in oocytes with an IC50 of 1.74 μM, and competed with G-FL with a Ki of 7.94 μM. The reverse experiment revealed that granisetron also competitively bound to muscarinic receptors (Ki = 6.5 μM). In behavioural studies scopolamine is used to block muscarinic receptors and induce a cognitive deficit, and centrally administered concentrations can exceed the IC50 values found here. It is therefore possible that 5-HT3 receptors are also inhibited. Studies that utilise higher concentrations of scopolamine should be mindful of these potential off-target effects.

Topical ophthalmic atropine sulfate is an important part of the treatment protocol in equine uveitis. Frequent administration of topical atropine may cause decreased intestinal motility and colic in horses due to systemic exposure. Atropine pharmacokinetics are unknown in horses and this knowledge gap could impede the use of atropine because of the presumed risk of unwanted effects. Additional information could therefore increase safety in atropine treatment.

Recently, low-concentration atropine (0.01%) has gained increased attention in controlling myopia progression with satisfying effects and minimal side effects. However, studies concerning responders to 0.01% atropine are limited. This retrospective observational cohort study aimed to determine the responder characteristics of 0.01% atropine in Asian children. One hundred forty children (aged between 3 and 15 years) receiving 0.01% atropine were analyzed for the factors influencing annual spherical equivalent changes (SE). The mean age was 9.13 (2.6) years, the mean baseline SE was - 1.56 (1.52) diopters (D), and the mean annual SE change was - 0.52 (0.49) D. A 58.63% responder rate (146/249) of myopic control was achieved with 0.01% atropine in our entire cohort under the criteria of less than 0.5 D of myopic progression annually. The subjects were stratified into 4 subgroups based on a cut-off point of baseline SE of - 1.5 D and baseline age of 9 years. The responder rate differed significantly with the highest being the youngest with the lowest myopia subgroups. Our results demonstrated that children with myopia better than - 1.5 D and younger than 9 years had the highest potential to achieve successful myopic control under 0.01% atropine therapy.

Theta frequency oscillations are a predominant feature of rhythmic activity in the hippocampus. We demonstrate that hippocampal area CA1 generates atropine-resistant theta population oscillations in response to metabotropic glutamate receptor activation under conditions of reduced AMPA receptor activation. This activity occurred in the absence of inputs from area CA3 and extra-ammonic areas. Field theta oscillations were co-expressed with pyramidal distal apical dendritic burst spiking and were temporally related to trains of IPSPs with slow kinetics. Pyramidal somatic responses showed theta oscillations consisted of compound inhibitory synaptic potentials with initial IPSPs with slow kinetics followed by trains of smaller, faster IPSPs. Pharmacological modulation of IPSPs altered the theta oscillation suggesting an inhibitory network origin. Somatic IPSPs, dendritic burst firing and stratum pyramidale interneuron activity were all temporally correlated with spiking in stratum oriens interneurons demonstrating intrinsic theta-frequency oscillations. Disruption of spiking in these interneurons was accompanied by a loss of both field theta and theta frequency IPSP trains. We suggest that population theta oscillations can be generated as a consequence of intrinsic theta frequency spiking activity in a subset of stratum oriens interneurons controlling electrogenesis in pyramidal cell apical dendrites.

The effect of 2- pyridine aldoxime methyl chloride (2-PAMCl) and atropine with or without curcumin was investigated in dichlorvos (2,2-dichlorovinyl dimethyl phosphate; DDVP) induced toxicity in rats. Rats were exposed to DDVP (2 mg/kg sub-cutaneously) once daily for the period of 21 days. Post DDVP exposure, rats were further treated with 2-PAMCl (50 mg/kg intramuscular, once daily) + atropine (10 mg/kg, i.m. once daily) with or without curcumin (200 mg/kg; oral; once daily) for further 21 days. We observed a significant increase in lipid peroxidation (LPO), reactive oxygen species (ROS), oxidized glutathione (GSSG), while there was a significant decrease in antioxidant enzymes, brain acetylcholinesterase (AChE) and 5-hydroxy tryptamine (5-HT) activity on DDVP exposure of rats. These alterations were restored significantly by co-administration of 2-PAMCl + atropine in DDVP exposed rats. Curcumin when co-supplemented with 2-PAMCl + atropine also significantly protected serum aspartate aminotransferase (AST) and restored brain AChE activity and 5-HT level in animals sub-chronically exposed to DDVP. Histopathological observations along with biochemical changes in rat blood and tissues revealed significant protection offered by 2-PAMCl + atropine against DDVP. The results indicate that DDVP-induced toxicity can be significantly protected by co-administration of 2-PAMCl + atropine individually, however, curcumin co-supplementation with 2-PAMCl + atropine provides more pronounced protection, concerning particularly neurological disorders.

This retrospective study evaluates the effectiveness of combining 0.05% atropine with MF60 contact lenses in managing rapid myopia progression in children over one year. The study involved three groups: the treatment group (TG) with 15 children (53% male, average age 12.9 ± 1.04), the MF group (MF) with 12 children (50% male, average age 12.8 ± 0.8) using only MF60 lenses, and the control group (CG) with 14 children (43% male, average age 12.1 ± 0.76). Baseline myopia and axial length (AL) were similar across groups, with the TG, MF, and CG showing -4.02 ± 0.70 D, -4.18 ± 0.89 D, -3.86 ± 0.99 D, and 24.72 ± 0.73 mm, 24.98 ± 0.70 mm, 24.59 ± 1.02 mm, respectively. Prior to the study, all groups exhibited significant myopia and AL progression, with no previous myopia control management. The treatment involved daily 0.05% atropine instillation, the use of MF60 lenses and increased outdoor activity. Biannual cycloplegic refraction and slit lamp evaluations confirmed no adverse reactions. After one year, the TG showed a significant reduction in myopia and AL progression (-0.43 ± 0.46 D, p < 0.01; 0.22 ± 0.23 mm, p < 0.01), whereas the CG showed minimal change (-1.30 ± 0.43 D, p = 0.36; 0.65 ± 0.35 mm, p = 0.533). The MF group also exhibited a notable decrease (-0.74 ± 0.45 D, p < 0.01; 0.36 ± 0.23 mm). Increased outdoor activity during the treatment year did not significantly impact myopia control, suggesting its limited additional effect in this cohort. The study concludes that the combination of 0.05% atropine and peripheral defocus soft contact lenses effectively controls myopia progression in children.

Myopia is the most common childhood refractive disorder. Atropine inhibits myopia progression, but its mechanism is unknown. Here, we show that myopia-prevention by atropine requires production of nitric oxide (NO). Form-deprivation myopia (FDM) was induced in week-old chicks by diffusers over the right eye (OD); the left eye (OS) remained ungoggled. On post-goggling days 1, 3, and 5, OD received intravitreally 20 µL of phosphate-buffered saline (vehicle), or vehicle plus: NO source: L-arginine (L-Arg, 60-6,000 nmol) or sodium nitroprusside (SNP, 10-1,000 nmol); atropine (240 nmol); NO inhibitors: L-NIO or L-NMMA (6 nmol); negative controls: D-Arg (10 µmol) or D-NMMA (6 nmol); or atropine plus L-NIO, L-NMMA, or D-NMMA; OS received vehicle. On day 6 post-goggling, refractive error, axial length, equatorial diameter, and wet weight were measured. Vehicle-injected goggled eyes developed significant FDM. This was inhibited by L-Arg (ED50 = 400 nmol) or SNP (ED50 = 20 nmol), but not D-Arg. Higher-dose SNP, but not L-Arg, was toxic to retina/RPE. Atropine inhibited FDM as expected; adding NOS-inhibitors (L-NIO, L-NMMA) to atropine inhibited this effect dose-dependently, but adding D-NMMA did not. Equatorial diameter, wet weight, and metrics of control eyes were not affected by any treatment. In summary, intraocular NO inhibits myopia dose-dependently and is obligatory for inhibition of myopia by atropine.

Background: Phenylephrine and atropine can cause serious adverse effects when applied in combination. We investigated the effect of phenylephrine eye drops combined with intravenous atropine on the cardiovascular system in patients under general anesthesia undergoing intraocular surgery. Methods: The effects of the drugs were observed through clinical study. Thirteen patients undergoing intraocular surgery under general anesthesia were observed in this study; all were injected intravenously with atropine due to the oculocardiac reflex during surgery. To study the combination of drugs, an in vivo study was performed on rats. Seventy-two standard deviation rats that received phenylephrine eye drops and intravenous atropine treatment under general anesthesia were assessed, of which 18 treated with these drugs simultaneously were administered normal saline, neostigmine or esmolol. Blood pressure and heart rate were recorded and analyzed. Findings: The age of the patients ranged from seven to 14 years old with an average age of 10.7 years old, and 11 patients were male. In patients, 5% phenylephrine eye drops combined with intravenous atropine led to a significant heart rate increase and the increase lasted 20 min. The significant increase in diastolic blood pressure and systolic blood pressure lasted for 15 and 25 min, respectively. From five to 25 min after intravenous atropine treatment, the systolic blood pressure and diastolic blood pressure were both more than 20% higher than that at baseline. In rats, the changes in blood pressure and heart rate were independent of the phenylephrine and atropine administration sequence but were related to the administration time interval. The neostigmine group showed a significant decrease in blood pressure after the increase from the administration of phenylephrine and atropine. Interpretation: Phenylephrine eye drops combined with intravenous atropine have obvious cardiovascular effects that can be reversed by neostigmine. This drug combination should be used carefully for ophthalmic surgery, especially in patients with cardio-cerebrovascular diseases.