Treating Intraoperative Bradycardia in Non-cardiac Surgery Patients With Atropine at Heart Rates Below 60 Versus 30 Beats Per Minute and Norepinephrine Requirements: the Randomized RAPID Trial

The RAPID trial is a randomized, single-center trial investigating whether giving atropine at heart rates below 60 beats per minute versus giving atropine only at heart rates below 30 beats per minute reduces the amount of norepinephrine needed to keep MAP above 65 mmHg in non-cardiac surgery patients with intraoperative bradycardia.

Start Date01 Apr 2025

Sponsor / Collaborator

University of Hamburg

CTRI/2025/03/083225

/ Not yet recruitingNot ApplicableIIT

Comparative Evaluation of Reduction in Salivary Flow Rate by using Sublingual Atropine Sulphate Drops during Dental Treatment Procedure. - NIL

Start Date31 Mar 2025

Sponsor / Collaborator-

NCT06389110

/ RecruitingPhase 3

Phase III Clinical Study to Evaluate the Efficacy of Alleance® (Atropine Sulfate 0.01%) as a Treatment to Delay the Progression of Myopia and Axial Ocular Elongation in Children.

Phase III clinical study to evaluate the efficacy of Alleance® (atropine sulfate 0.01%) ophthalmic solution through the incidence of unexpected adverse events, changes in Best Corrected Visual Acuity (BCVA), changes in intraocular pressure, changes in the amplitude of accommodation, compared to placebo, as a treatment to delay the progression of myopia and axial ocular elongation in children.

Start Date15 Mar 2025

Sponsor / Collaborator

Laboratorios Sophia SA de CV

100 Clinical Results associated with Atropine Sulfate

100 Translational Medicine associated with Atropine Sulfate

100 Patents (Medical) associated with Atropine Sulfate

35,173

Literatures (Medical) associated with Atropine Sulfate

01 Jun 2025·PHYTOMEDICINE

Revealing the gastric protective mechanism of Physochlaina physaloides (L) G. Don. with clinical orientation: PPAR/NF-κB signalling pathway activation

Article

Author: Cui, Hongwei ; Li, Minhui ; Yu, Lan ; Chen, Dongxue ; Li, Siqi ; Feng, Wanze

BACKGROUND:

Gastrointestinal diseases are global health issues. Current drugs for gastrointestinal diseases cause discomfort and toxicity; consequently, the use of traditional medicines and their extracts has gained attention in recent years. Physochlaina physaloides (L) G. Don. (P. physaloides) is traditionally used for diarrhoea and gastroenteritis; however, its material basis and mechanism of action for gastric injury have not been fully studied.

PURPOSE:

This study aims to explore P. physaloides and their protective effects on gastric injury, together with the potential mechanisms.

STUDY DESIGN AND METHODS:

We constructed chronic gastritis and gastric ulcer models in rats using 56 % ethanol and anhydrous ethanol, respectively. Additionally, we screened gastric injury pathways via transcriptomics and the gene expression omnibus (GEO) database. Subsequently, we constructed an ethanol-stimulated GES-1 cell model and screened the active fraction of P. physaloides based on the cell survival rate and antioxidant activity. The effect of the active fraction of P. physaloides was investigated via tissue structure (HE staining), mucus secretion (PAS staining), anti-inflammatory activity, antioxidant activity, and gastric acid secretion levels. We employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine the active components of P. physaloides and the drug components in blood, before investigating the mechanisms via immunofluorescence, transcriptomic, metabolomics, network pharmacology, molecular docking, qRT-PCR, western blotting, and flow cytometry.

RESULTS:

The occurrence of gastritis, gastric ulcer, and gastric cancer is related to the PPAR/NF-κB signalling pathway, with decreased expression of FABP3 and PPARγ, and increased expression of Bcl-2 and TNF-α. The n-butanol fraction of P. physaloides (BPP) showed significant improvement in cell survival and antioxidant activity in vitro. BPP also alleviated inflammation and oxidative stress in rat models, including by upregulating CAT, GSH, SOD, IL-10, PGE₂; downregulating VEGFA, IL-6, IL-8, TNF-α, and NO; improving pathological damage; restoring mucus levels; and reducing gastric acid secretion and macrophage expression. BPP and its active components, anisodamine and hyoscyamine, upregulated the expression of PPARα, PPARγ, CPT1, and FABP3, and downregulated NF-κB p65, thereby regulating the PPAR/NF-κB signalling pathway for gastroprotection. The BPP and its active components did not significantly increase the expression of GPX4 and SLC7A11, nor did they reduce the production of ROS. Therefore, their effects are unrelated to ferroptosis.

CONCLUSION:

This study provides the first evidence of the effectiveness of BPP in the prevention of gastric ulcers and treatment of chronic gastritis. We adopted a multidisciplinary approach to demonstrate that BPP and its active components, anisodamine and hyoscyamine, protect against ethanol-induced gastric injury by regulating the PPAR/NF-κB and non-ferroptotic cell death pathways. BPP and its active components can target PPARγ and FABP3 and may have clinical application prospects to prevent gastric injury, which has unique advantages. These findings provide a scientific foundation for gastroprotection and expand the clinical applications of BPP.

01 Jun 2025·PLANT PHYSIOLOGY AND BIOCHEMISTRY

Manipulation of artificial light environment improves tropane alkaloids content in Atropa belladonna L.

Article

Author: Zhang, Shaoke ; Chu, Leixia ; Yang, Linlin ; Zhang, Di ; Feng, Weisheng ; Wan, Jie ; Dong, Ning ; Gu, Xupeng ; Li, Hanwei ; Zhou, Shengwei ; Zhang, Feiyu ; Dong, Chengming

Light quality exerts a vital influence on the accumulation of secondary metabolites in medicinal plants. Atropa belladonna L. serves as a primary source plant of tropane alkaloids (TAs). Nevertheless, in agricultural production, its application is restricted due to the relatively low content of alkaloids. This study explored the impacts of red, yellow, blue, and white light on the growth of A. belladonna and the biosynthesis of TAs. Through phenotypic and physiological analyses, it was found that red-light had the most significant effect on A. belladonna. Red-light remarkably increased the content of TAs, enlarged the leaf area, extended the stomatal length, and elevated the ammonium nitrogen level. It also enhanced the activities of ornithine decarboxylase, nitrate reductase, and glutamine synthetase, which are essential for nitrogen assimilation. Transcriptomic analysis identified GDHA, At2g42690, and PAO5 as key genes with upregulated expression in the putrescine biosynthesis pathway, where putrescine is an important precursor of TAs. Metabolomic data confirmed that the levels of scopolamine, hyoscyamine, and their precursors increased under red-light. Subsequent qPCR verification under red/white light treatments consistently showed the upregulation of these genes, further confirming their roles in the synthesis of TAs. Moreover, red-light activated photosynthesis-related genes and transcription factors, indicating a coordinated regulatory relationship between light signal transduction and metabolic pathways. This study has preliminarily elucidated the potential mechanism by which red-light promotes the accumulation of TAs through enhancing nitrogen metabolism and precursor synthesis, providing a theoretical basis for improving the quality of A. belladonna and optimizing agricultural production.

01 Jun 2025·NEUROPHARMACOLOGY

Hippocampus muscarinic M4 receptor mRNA expression may influence central cholinergic activity, causing fear memory strengthening by peripheral adrenaline

Article

Author: Seixas, Rafaela ; Martinho, Raquel ; Azevedo, Márcia ; Oliveira, Ana ; Serrão, Paula ; Silva, Elisabete ; Silva, Soraia ; Moreira-Rodrigues, Mónica

Adrenaline (Ad) strengthens contextual fear memory by increasing blood glucose, possibly enhancing hippocampus acetylcholine synthesis. Nevertheless, it is unclear if peripheral Ad influences the cholinergic system, contributing to contextual fear memory strengthening. We aimed to evaluate whether peripheral Ad alters muscarinic receptor expression and if the cholinergic system is involved in peripheral Ad contextual fear memory strengthening effect. Wild-type (WT) and Ad-deficient male mice (129 × 1/SvJ) underwent a fear conditioning procedure followed by intraperitoneal pre-training and pre-context administration of Ad (0.1 mg/kg), atropine (10 mg/kg), methylatropine (0.5 mg/kg), Ad (0.1 mg/kg) plus atropine (10 mg/kg) or vehicle (NaCl, 0.9%). Shock responsiveness and freezing behaviour were accessed. Hippocampal M₁, M₂, and M₄ mRNA expression were evaluated. Ad-deficient mice presented decreased hippocampal muscarinic M₄ subtype receptor mRNA expression compared to WT mice. In Ad-administered Ad-deficient mice, hippocampal muscarinic M₄ subtype receptor mRNA expression increased compared with vehicle-administered Ad-deficient mice. On the context day, atropine-administered WT mice presented decreased freezing behaviour compared to vehicle or methylatropine-administered WT mice. Moreover, Ad plus atropine-administered Ad-deficient mice led to decreased freezing behaviour compared to Ad-administered Ad-deficient mice. In conclusion, Ad-deficient mice's contextual fear memory impairment was associated with hippocampal muscarinic M₄ subtype receptor down expression, which was reversed by Ad. This may be related to contextual fear memory consolidation or retrieval induced by peripheral Ad. Furthermore, the effect of Ad contextual fear memory might be due to increased hippocampus muscarinic subtype M₄ expression, which may contribute to increased cholinergic activity in the central nervous system.

News (Medical) associated with Atropine Sulfate

01 Feb 2025

·www.globenewswire.com

Vyluma Announces Acceptance of Drug Application for NVK002 by China’s National Medical Products Administration (NMPA)

Jan. 29, 2025 -- Vyluma, Inc. (“Vyluma”), a biopharmaceutical company advancing novel treatments for refractive errors, announced today that the National Medical Products Administration (NMPA) of China has accepted the drug application from Zhaoke Ophthalmology Limited (“Zhaoke”) for its lead compound, NVK002 (low-dose atropine 0.01%), as a potential treatment for myopia progression in children. NVK002, developed by Vyluma and licensed to Zhaoke, is a proprietary, investigational, preservative-free eye drop administered nightly, targeting pediatric patients with myopia. Acceptance of the drug application by the NMPA marks an essential step in introducing NVK002 as a potential therapeutic option for managing myopia in children across China. “NMPA acceptance of the drug application for NVK002 is a significant milestone for Vyluma and underscores our commitment to addressing the global pediatric myopia epidemic,” said George Zorich, Chairman and CEO of Nevakar, Inc., and acting President of Vyluma, Inc. “China is home to one of the highest rates of pediatric myopia in the world, making this approval process critical for ensuring access to an innovative treatment that could dramatically impact the vision and quality of life for millions of children later in life. This acceptance is a testament to our dedication to advancing effective, science-based solutions for pediatric eye health worldwide.” The drug application is based on the first Phase III clinical trial (“Mini-CHAMP”) conducted by Zhaoke in China. The trial involved 16 centers and enrolled 526 patients. Mini-CHAMP successfully met its primary efficacy endpoint, achieving statistically and clinically meaningful differences versus placebo, and demonstrated strong safety and efficacy and high patient tolerance. A second Phase III clinical trial (“China CHAMP”) from Zhaoke completed the last patient last visit in August 2024. The trial involves 18 centers and enrolled 777 patients. The top-line results of China-CHAMP showed significant efficacy and favorable safety profile of NVK002, further supporting the drug as a potential treatment for myopia progression in children. With its acceptance by the NMPA, NVK002 is now under regulatory review across three major global markets: the United States, the European Union, and China. This milestone reinforces Vyluma’s vision of bringing innovative pharmaceutical solutions to children worldwide and advancing the treatment of myopia progression globally. Vyluma is a clinical-stage biopharmaceutical company with a focus on pharmaceutical treatments for refractive errors of the eye. Vyluma’s pipeline of therapies is led by NVK002, an investigational, preservative-free, low-dose atropine eye drop to treat the progression of myopia in children aged 3 years and older. Vyluma has a robust pipeline of other assets in various stages of development which address important unmet treatment needs of patients with refractive errors or eye pain. Vyluma itself is a subsidiary of Nevakar Inc., a holding company whose subsidiaries are engaged in developing products for the ophthalmic and injectable markets. For additional information please visit www.vyluma.com. Nevakar Inc. is a fully integrated privately held, late-stage biopharmaceutical company with an extensive portfolio of products in the ophthalmic and injectable areas. Founded in 2015, and headquartered in Bridgewater, New Jersey, the Company is focused on developing and commercializing innovative products to address unmet medical needs, thereby improving patients’ quality of life and healthcare outcomes. Nevakar utilizes the US 505(b)(2) regulatory pathway, along with its proven expertise in the development of novel and proprietary sterile pharmaceutical products to identify, develop, and obtain regulatory approval for its products. Additional information is available at www.nevakar.com. Founded in 2017 in China, Zhaoke (SEHK: 6622) is a leading ophthalmic pharmaceutical company dedicated to the research and development, manufacturing and commercialization of therapies that address significant unmet medical needs in the world. The company was listed on the Main Board of the Hong Kong Stock Exchange on 29 April 2021. Zhaoke Ophthalmology has a comprehensive drug portfolio of innovative and generic treatments covering major eye diseases across both the front- and the back-of-the-eye. Currently, the company is focusing on major near-term development programs that are in the pre-registration stage, pivotal phase III clinical trial and other stages in clinical trial for the treatment of five respective major ophthalmic diseases, i.e. dry eye disease, myopia, wet AMD, presbyopia and cornea epithelial defects. Many of the drugs are being produced in its state-of-the-art and fully functional development and production facility in Nansha, Guangzhou, Guangdong Province in China. Through its ambitious growth strategy, including partnering with domestic and international pharmaceutical companies, Zhaoke Ophthalmology’s goal is to become a global leader in ophthalmology. The content above comes from the network. if any infringement, please contact us to modify.

Clinical Result

22 Jan 2025

·www.fiercepharma.com

Kindeva unit Meridian Medical snares $129M to supply US with nerve agent antidote

St. Louis-based Kindeva snared a $129 million contract to supply the U.S. with the chemical nerve agent antidote autoinjector DuoDote. Meridian Medical Technologies, a unit of CDMO Kindeva, snared a $129 million contract to supply the United States with the chemical nerve agent antidote autoinjector DuoDote.The FDA-approved, dual-chamber autoinjector contains atropine and pralidoxime chloride and is used to counteract the effects of organophosphorus nerve agents and insecticides, the company said in a Jan. 16 press release.Kindeva, a CDMO focused on drug delivery devices, said the DuoDote autoinjectors will be produced and distributed from its fill-finish facility in St. Louis.“This contract underscores the ongoing importance of maintaining readiness against potential threats,” Milton Boyer, Kindeva’s chief executive, said in the release. “With our extensive experience in this space, we are proud to continue supporting the U.S. government’s efforts to protect public health and safety.”Kindeva operates manufacturing and R&D facilities in the U.S. and U.K. Last year, the company secured a 33 million pound sterling ($42.1 million at the time) contract from the U.K.’s Life Sciences Innovation Manufacturing Fund to boost its inhaler production and sustainability efforts.The grant was part of the country’s move to support the development and production of inhalers that utilize new propellants with lower global warming potential.

16 Jan 2025

·www.pharmaceutical-technology.com

Meridian Medical wins $129m US gov contract for nerve agent antidote supply

Meridian Medical’s DuoDote will be stockpiled as part of the Strategic National Stockpile’s (SNS) CHEMPACK programme. Image credit: Lucky-photographer via Shutterstock. Kindeva Drug Delivery division Meridian Medical Technologies has won a new contract worth up to $129m from the US Government for the supply of its DuoDote chemical nerve agent antidote autoinjectors to the Strategic National Stockpile (SNS). Managed by the Administration for Strategic Preparedness and Response (ASPR) within the US Department of Health and Human Services (HHS), the SNS contains medicines and devices for lifesaving care, which are intended for use as stopgap buffers when the immediate supply of such materials may not be available or sufficient. The DuoDote dual-chamber autoinjector contains atropine and pralidoxime chloride and was approved by the US Food and Drug Administration (FDA) in 2006. It is indicated for the treatment of poisoning from organophosphorus nerve agents and organophosphorus insecticides. Perhaps the nerve agent most well-known to the general public, sarin has been in use since World War II and became infamous in more recent times for its 2013 use on civilians in Syria during the Bashar al-Assad regime. The DuoDote autoinjectors will be manufactured at Kindeva Drug Delivery’s facility in St Louis, Missouri. They will then be stockpiled and available for rapid deployment as part of the SNS CHEMPACK programme. SNS CHEMPACK is an ASPR initiative in which containers of nerve agent antidotes are placed in secure locations around the US to enable rapid response to chemical incidents. Kindeva CEO Milton Boyer commented: “As a trusted partner to the SNS, this contract underscores the ongoing importance of maintaining readiness against potential threats. “Our long-standing partnership with the SNS reflects our commitment to national preparedness and our ability to deliver crucial medical countermeasures when they are needed most. With our extensive experience in this space, we are proud to continue supporting the US Government’s efforts to protect public health and safety.” Kindeva recently partnered with Emervax to co-develop a vaccine delivery solution for viruses including mpox and yellow fever. Kindeva Drug Delivery was formerly known as 3M Drug Delivery Systems and rebranded itself in 2020, following its acquisition by Altaris Capital Partners in a deal valued at $650m.

Drug ApprovalVaccineAcquisition

100 Deals associated with Atropine Sulfate

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KEGG	Wiki	ATC	Drug Bank
D02069	Atropine Sulfate	A03BA01 S01FA01	-

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Indication	Country/Location	Organization	Date
Myopia	Australia	Aspen Pharmacare Australia Pty Ltd.	13 Sep 2021
Heart Arrest	United States	Accord Healthcare, Inc.	29 Sep 2020
Mushroom Poisoning	United States	Accord Healthcare, Inc.	29 Sep 2020
Bradycardia	United States	Fresenius Kabi USA LLC	26 Jan 2018
Amblyopia	United States	Rising Pharmaceuticals, Inc.Startup	18 Jul 2014
Arrhythmias, Cardiac	China	Chengdu First Pharmaceutical Co. Ltd.	01 Jan 1981
Pain	China	Chengdu First Pharmaceutical Co. Ltd.	01 Jan 1981
Poisoning	China	Chengdu First Pharmaceutical Co. Ltd.	01 Jan 1981
Organophosphate Poisoning	United States	Meridian Medical Technologies LLC	15 May 1973
Ophthalmoplegia	Japan	Santen Pharmaceutical Co., Ltd.	31 Mar 1970
Cycloplegia	Japan	ROHTO NITTEN Co., Ltd.	20 Jul 1968
Mydriasis	Japan	ROHTO NITTEN Co., Ltd.	20 Jul 1968

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Myopia, Degenerative	Phase 3	United States	Ocumension Therapeutics	01 Apr 2021

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT06366087 (SABER, CTgov)	Phase 1	-	46	Atropine Sulfate Ophthalmic Solution USP, 1% (Sublingual)	lvydqvstqu(pclofwmghs) = cjqdloxxrn uvqwwbxqxc (ntczparebu, 23.0) View more	-	04 Apr 2025
				Atropine Sulfate Injection, USP 8 mg/20 mL (0.4 mg/mL) (Intramuscular)	lvydqvstqu(pclofwmghs) = zamnqzcpfy uvqwwbxqxc (ntczparebu, 19.0) View more
NCT06209281 (Mini-CHAMP, NEWS) Manual	Phase 3	Myopia	526	NVK002	uayxslobxa(pdtxoihlum) = 达到了其主要疗效终点。 pmtsumcabq (hxltsjflrt ) Met View more	Positive	07 Jan 2025
				Placebo
NCT03750656 (HyTa Stent, CTgov)	Phase 4	Lower Urinary Tract Symptoms	5	Hyoscyamine (Hyoscyamine)	ulelovetmu(hwoqczfjgb) = ojqixhvfvu dpwrraqfpk (oeinufmnyf, krtqpppeot - bejwhufvvo) View more	-	03 Dec 2024
				Tamsulosin (Tamsulosin)	ulelovetmu(hwoqczfjgb) = xlqoidkfvi dpwrraqfpk (oeinufmnyf, rveqoloehe - eaflmedqzq) View more
NCT03350620 (CHAMP, CTgov)	Phase 3	Myopia	670	NVK-002 Concentration 1 (NVK-002 Concentration 1)	zmzocqtxef = xxvnfbabzs eanpzmytzc (lhcaitzril, omthvkvyod - qenaenbjof) View more	-	27 Nov 2024
				NVK-002 Concentration 2 (NVK-002 Concentration 2)	zmzocqtxef = eojugpvlct eanpzmytzc (lhcaitzril, sppcdmkkmp - pkqjtonxqq) View more
NCT06209320 (China CHAMP, Corporate Publications \| NEWS) Manual	Phase 3	Myopia	-	NVK002	yefaczttyz(xvswfwuepi) = NVK002滴眼液组（0.01%和0.02%剂量）对比安慰剂组在主要疗效指标上有统计学意义的显著性差异，NVK002滴眼液组优于安慰剂组，且具有剂量依赖。 cvtgipsmfg (donahbojtr ) View more	Positive	24 Oct 2024
				Placebo
NCT03374306 (CTgov)	Not Applicable	Myopia	71	Atropine (0.01%) (Atropine 0.01%)	codvljbhso(qlwpmguyic) = rswvckvyua yediajfuwo (gkxlxpwnvp, 0.39) View more	-	16 Oct 2024
				Artificial tear (Artifical Tear)	codvljbhso(qlwpmguyic) = aipltitzsg yediajfuwo (gkxlxpwnvp, 0.41) View more
EURETINA2024 Manual	Not Applicable	Myopia	97	0.01% Atropine Eye Drops	ehlrxyaxoh(tqakulrnnw) = fkygbnmxpa nlpzsijura (xiyrwaghlt, 0.01 - 0.19) View more	Positive	19 Sep 2024
				0.1% LAtropineose Atropine Eye Drops	ehlrxyaxoh(tqakulrnnw) = nbqlkhnoid nlpzsijura (xiyrwaghlt, -0.01 to 0.17) View more
NCT03699423 (Pubmed \| J Ocul Pharmacol Ther) Manual	Phase 1	Myopia	57	0.01% atropine eye drops	ibxlbqhsha(tlxsyibtvz) = vdrahovmvz banelbscfe (jnxxvotjyo ) View more	Positive	15 Apr 2024
				0.02% atropine eye drops	ibxlbqhsha(tlxsyibtvz) = xsanxdxbnz banelbscfe (jnxxvotjyo ) View more
APAO2024	Not Applicable	Myopia	-	Atropine 0.01%	jutuczclph(lkkifvgxgw) = mmcsjsfvth qvrqartyit (nkyiofqnzp ) View more	-	22 Feb 2024
APAO2024	Not Applicable	Myopia	96	0.01% Atropine (AOK group)	izbqyjtost(rdzitnncew) = ljeluxjygp xnxetpxvxt (jzjdqckcgo ) View more	Positive	22 Feb 2024
				0.01% Atropine (OK group)	izbqyjtost(rdzitnncew) = aopqyspxzf xnxetpxvxt (jzjdqckcgo ) View more

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