Delving into the Latest Updates on Scopolamine Hydrobromide Hydrate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

INSCOP spray, Scopolamine, Scopolamine HBr

+ [7]

Target

mAChRs

Mechanism

mAChRs antagonists(Muscarinic acetylcholine receptor antagonists)

Therapeutic Areas

Infectious DiseasesNervous System DiseasesEndocrinology and Metabolic Disease+ [2]

Active Indication

Bipolar DisorderHyperemesis GravidarumMotion Sickness+ [7]

Inactive Indication

Depressive Disorder, Major

Originator Organization

KYORIN Pharmaceutical Co., Ltd.

Active Organization

Repurposed Therapeutics, Inc.

Chengdu First Pharmaceutical Co. Ltd.

KYORIN Pharmaceutical Co., Ltd.

Inactive Organization

Defender Pharmaceuticals, Inc.

Drug Highest PhaseApproved

First Approval Date

JP (01 Dec 1961),

AnesthesiaParkinson Disease, Postencephalitic

Regulation-

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Structure

Molecular FormulaC17H28BrNO7

InChIKeyLACQPOBCQQPVIT-SEYKEWMNSA-N

CAS Registry6533-68-2

Qifu Yin (QFY) originates from "Jingyue Quanshu · Volume 51 · New Fang Bazhen · Buzhen" a work by Zhang Jingyue, a distinguished Chinese medical practitioner from the Ming Dynasty. QFY is composed of Ginseng Radix et Rhizoma, Rehmanniae Radix Praeparata, Angelicae Sinensis Radix, Atractylodis Macrocephalae Rhizoma, Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle, Ziziphi Spinosae Semen, and Polygalae Radix. QFY is frequently employed to address memory loss and cognitive impairment stemming from vascular dementia, Alzheimer's disease (AD), and related conditions. Our findings indicate that QFY can mitigate nerve cell damage. Moreover, the study explores the impact of QFY on the calcium ion pathway and sphingolipid metabolism in mice with myocardial infarction, presenting a novel perspective on QFY's mechanism in ameliorating myocardial infarction through lipidomics. While this research provides an experimental foundation for the clinical application of QFY, a comprehensive and in-depth analysis of its improvement mechanism remains imperative.

AIM OF THE STUDY:

To clarify the regulatory mechanism of QFY on intestinal microecology in mice with memory impairment (MI).

MATERIAL AND METHODS:

The memory impairment mouse model was established by intraperitoneal injection of scopolamine hydrobromide. Kunming (KM) mice were randomly divided into blank group, Ginkgo tablet group (0.276 g/kg), QFY high, medium and low dose groups (17.2 g/kg, 8.6 g/kg, 4.3 g/kg). The effect on memory ability was evaluated by open field and step-down behavioral experiments. The morphological changes of nerve cells in the hippocampus of mice were observed by pathological method. The contents of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GSH-Px) in the brain tissue of mice were detected. The expression levels of CREB, Brain-Derived Neurotrophic Factor (BDNF) and Recombinant Amyloid Precursor Protein (APP) in the hippocampus of mice were determined using immunohistochemistry. The expression of N-methyl-D-aspartate receptor (NMDAR) and cAMP response element binding protein (CREB) related factors in the serum of mice was analyzed by ELISA. The levels of apoptosis signal-regulating kinase-1 (ASK1) and c-Jun N-terminal kinase (JNK) mRNA in the hippocampus were detected by quantitative real-time fluorescence polymerase chain reaction (qPCR). The intestinal feces of mice were collected, and the 16 S rDNA technology was used to detect the changes in intestinal microbiota microecological structure of feces in each group.

RESULTS:

Behavioral experiments showed that the high-dose QFY group exhibited a significant increase in exercise time (P<0.05) and a decrease in diagonal time (P<0.05) compared to the model group. The medium-dose group of QFY showed a reduction in diagonal time (P<0.05). Additionally, the latency time significantly increased in the medium and high-dose groups of QFY (P<0.01). The number of errors in the low, medium and high dose groups was significantly decreased (P<0.05, P<0.01, P<0.01). The nerve cells in the CA1 and CA3 regions of QFY-treated mice demonstrated close arrangement and clear structure. Furthermore, the content of SOD significantly increased (P<0.01) and the content of MDA significantly decreased (P<0.05) in the low and high-dose QFY groups. The content of CAT in the medium-dose group significantly increased (P < 0.05). Immunohistochemical analysis showed a significant reduction in the number of APP expression particles in the CA1 and CA3 regions of all QFY groups. Moreover, BDNF expression significantly increased in the medium and high-dose groups, while CREB expression significantly increased in the low and medium-dose groups of QFY within the CA1 and CA3 regions. Serum analysis revealed significant increases in CREB content in the low, medium, and high dose groups of QFY (P<0.01, P<0.05, P<0.05), and decreases in NMDAR content across all QFY dose groups (P<0.01). PCR analysis showed a significant decrease in the contents of ASK1 and JNK in the medium-dose group (P<0.01). Microecological analysis of intestinal microbiota demonstrated a significant restoration trend in the relative abundance of Fusobacteria, Planctomycetes, and Verrucomicrobia (P<0.01 or P<0.05) at the phylum level in the QFY groups. At the genus level, Akkermansia, Paramuribaculum, Herminiimonas, Erysipelatoclostridium and other genera in the QFY groups showed a significant trend of relative abundance restoration (P<0.01 or P<0.05).

CONCLUSION:

QFY can improve the memory of MI animals induced by scopolamine hydrobromide by restoring the homeostasis of intestinal microbiota and regulating related indexes in serum and brain tissue.

01 Oct 2024·BULLETIN OF EXPERIMENTAL BIOLOGY AND MEDICINE

Correction of Disorders in Psychoneurological Status and Functioning of Progenitor Cells of the Nervous Tissue with NF-κB Inhibitor under Conditions of Alzheimer’s Disease Modeling

Article

Author: Chaykovskyi, A V ; Simanina, E V ; Polyakova, T Yu ; Zyuz'kov, G N ; Zhdanov, V V ; Agafonov, V I ; Miroshnichenko, L A

We studied the effect of NF-κB blockade on the state of various pools of progenitor cells of the nervous tissue and the psychoneurological status of experimental animals with modeled Alzheimer's disease. Administration of scopolamine hydrobromide to C57BL/6 mice for 4 weeks was accompanied by the development of "persistent" disturbances in the orientation and exploratory behavior and mnestic function. An ameliorating effect of the NF-κB inhibitor on these cognitive disorders typical of senile dementia was revealed. At the same time, we observed an increase in the content of neural stem cells and committed neuronal precursors in the subventricular zone of the brain.

01 Sep 2024·CURRENT EYE RESEARCH

A Rabbit Dry Eye Model Induced by Subcutaneous Scopolamine

Article

Author: Duan, Sujuan ; Huang, Shitong ; Tian, Bishan ; Huang, Guofu ; Zhou, Shiyou

PURPOSE:

To establish and characterize a dry eye model in New Zealand rabbits by subcutaneous injections of scopolamine hydrobromide (SCOP).

METHODS:

Twenty New Zealand male rabbits were injected subcutaneously SCOP for 14 consecutive days; subcutaneous saline was used as a negative control. The correlated clinical parameters of ocular surface dryness were detected in vivo using tear secretion and corneal fluorescein staining. The expression of IL-1β and TNF-α on the ocular surface and in lacrimal glands were analyzed by real-time PCR and western blot on the 14th day. The expression of Mucin-5 subtype AC (MUC5AC) was detected by Immunofluorescence staining in conjunctival tissue.

RESULTS:

The SCOP-treated rabbits exhibited significantly decreased aqueous tear secretion and increased corneal fluorescein staining scores over time. Both the mRNA expression levels and the protein expression levels of IL-1β and TNF-α were significantly increased after SCOP treatment compared with those after saline treatment. The loss of conjunctival MUC5AC was found in the SCOP-injected rabbits. Some infiltrated inflammatory cells and atrophic acinar cells were observed in the lacrimal gland after SCOP treatment. The disordered structures of the ocular surface and lacrimal glands were also observed.

CONCLUSIONS:

This study showed that repeated subcutaneous SCOP injections successfully elicited some of the typical dry eye symptoms commonly seen in humans.

11

News (Medical) associated with Scopolamine Hydrobromide Hydrate

31 Jan 2024

·www.pharmaceutical-technology.com

Defender’s plans for motion sickness nasal gel stop with FDA rejection

Nasa is helping with Defender’s development of DPI-386, as astronauts are particularly susceptible to motion sickness in space. Image credit: Shutterstock/Supamotionstock.com. The FDA has decided to not approve Defender Pharmaceuticals’ intranasal scopolamine candidate for motion sickness, issuing a complete response letter (CRL) to the US-based company. Defender’s drug, known as DPI-386, is indicated for the prevention of nausea and vomiting induced by motion in adults. Defender’s CEO Barry I Feinberg said the company plans on scheduling a formal meeting with the FDA to discuss the issues raised and to create a plan going forward, in a 30 January press release. DPI-386 is a nasal gel version of the antimuscarinic drug scopolamine, first approved by the FDA as a transdermal patch in 1979, according to the drug’s label . Currently, patches are placed behind the ear and work with high efficacy by depressing the parasympathetic nervous system. The gel could be particularly useful for astronauts and military personnel who are frequently exposed to motion. Nasa joined forces with Epiomed Therapeutics to develop a fast-acting nasal spray version of scopolamine in 2012. According to the St Louis Post-Dispatch , Defender purchased Epiomed in 2014 and was founded the same year. Headquartered in St Louis, Missouri, the company has also worked with the United States Naval Medical Research Unit. See Also: Tyra Biosciences’ TYRA-300 gains FDA rare paediatric disease status Revolo advances plans to tackle eosinophilic esophagitis with orphan drug tag Defender’s formulation aims for rapid absorption to induce quicker onset. In a Phase III trial more than 500 participants, who usually get motion sick, had improved symptoms after being exposed to open sea conditions while using DPI-386. Subjects who received the nasal gel demonstrated lower incidences of vomiting and fewer requests for rescue medication compared to a placebo group. The incidence of moderate to severe nausea was also lower. In a September 2023 statement announcing the new drug application (NDA) acceptance, Defender said results from five phase III trials were submitted as evidence. The NDA was assigned priority review status by the FDA at the request of the US Navy. Feinberg added: “We remain confident that our intranasal scopolamine is a safe and effective therapy for the prevention of motion sickness, and we will work closely with the FDA to ensure that we can bring this innovative new product to the market.” Defender is also exploring the use of DPI-386 in major depressive disorder (MDD) with suicide ideation, chemical exposure accidents, and virtual reality sickness. In October 2023, Defender announced further collaborations with Nasa to study DPI-386 in Phase II trials to mitigate G-transition-induced motion sickness and enhance sensorimotor performance. Scopolamine recently made the news beyond the healthcare sector after rising incidences of it being linked to criminal activity. In June 2023, the US Embassy in Colombia highlighted the sedative side effects of the drug are being increasingly used to target tourists in the country. In certain doses, the drug can cause unconsciousness for 24 hours or more. Scopolamine was also the first drug to infamously garner the “truth serum” tag.

Phase 3Phase 2NDAClinical ResultDrug Approval

30 Jan 2024

·www.globenewswire.com

Defender Pharmaceuticals Receives Complete Response Letter from the U.S. Food and Drug Administration for its Intranasal Scopolamine (DPI-386) New Drug Application for the Prevention of Nausea and Vomiting Induced by Motion in Adults

ST. LOUIS, Jan. 30, 2024 (GLOBE NEWSWIRE) -- Defender Pharmaceuticals, Inc. (the “Company” or “Defender”), a privately held life sciences company based in St. Louis, today announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) in response to the Company’s New Drug Application (NDA) for intranasal scopolamine (DPI-386) for the prevention of nausea and vomiting induced by motion in adults. “Following our review of the CRL, we plan on scheduling a formal meeting with the FDA to fully understand the issues raised in the CRL so we can develop and implement a comprehensive action plan,” said Barry I. Feinberg, M.D., President & CEO of Defender Pharmaceuticals. “We remain confident that our intranasal scopolamine is a safe and effective therapy for the prevention of motion sickness, and we will work closely with the FDA to ensure that we can bring this innovative new product to the market.” About intranasal scopolamine (DPI-386) Development ProgramDefender has worked with the United States Naval Medical Research Unit (NAMRU-D) and the National Aeronautics and Space Administration (NASA) on its intranasal scopolamine development program that is focused on specific military personnel and astronauts. To date, more than 1,300 patients have participated in Defender clinical studies, including over 500 participants in the DPI-386-MS-33 study. Given the successful outcome of DPI-386-MS-33, Defender has submitted a New Drug Application (NDA) to the Food and Drug Administration (FDA) for DPI-386 Nasal Gel for the prevention of nausea and vomiting induced by motion in adults. Defender is also developing intranasal formulations designed to treat a wide variety of indications. We believe these new products have the potential to help safeguard health across civilian and military populations. About Motion Related DiscomfortCertain motions cause discomfort in individuals while engaged in a variety of leisure or travel related activities. Most forms of travel, whether on land, in the air, or on the water, can trigger symptoms such as nausea and vomiting (example: flying, boating/fishing, car, bus, and train). Symptoms induced by motion can also have a detrimental impact on the ability of various military personnel and astronauts to perform assigned duties, potentially impacting readiness and negatively impacting resources. Motion related discomfort is a common and transient response to unfamiliar or unnatural motion or contradictory spatial sensory information, resulting in decrements to performance of tasks, pallor, cold sweating, nausea and vomiting. Prolonged exposure to certain motions may induce sopite-related symptoms such as loss of drive and concentration, drowsiness, sleepiness, apathy, depression, and a feeling of impending doom. About Defender Pharmaceuticals, Inc.Defender Pharmaceuticals, Inc., located in St. Louis, MO, is a privately held life sciences company focused on discovering, developing and commercializing medicines to help safeguard health across civilian and military populations. Our work with the Department of Defense, NASA, the Department of Veterans Affairs, and other institutions advance our mission to improve the health of patients and help make the world a more secure place. Additional information can be found at www.defenderpharma.com. Cautionary Note on Forward-Looking Statements Various statements in this press release, including but not limited to statements regarding Defender’s plans to continue the intranasally administered scopolamine HBr development program and pursue FDA approval, are forward-looking statements under securities law. Such forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statements. Examples of forward-looking statements include, among others, statements we make regarding our product candidates and the development thereof, such as the Company’s intranasal scopolamine motion sickness development program; the therapeutic potential of our intranasally administered scopolamine HBr product candidate; the Company’s regulatory plans and timelines for intranasally administered scopolamine HBr. The process by which investigational therapies, such as intranasal scopolamine, could potentially lead to an approved product is long and subject to highly significant risks. Other risk factors relevant to Defender include our reliance on third-party contract research organizations; the reliance of Defender on contract manufacturers to supply its products for research, development and commercialization and the risk of supply interruption from such contract manufacturers; the timing, plans and reviews by regulatory authorities of marketing applications such as NDAs for intranasally administered scopolamine HBr; alignment with the FDA on the regulatory pathway to approval for intranasally administered scopolamine HBr; market acceptance for approved product; competition; the possible impairment of, inability to obtain, and costs to obtain intellectual property rights; possible safety or efficacy concerns that could emerge as new data are generated during development and following commercialization; and general business, financial, and accounting risks and litigation. The forward-looking statements contained in this press release reflect Defender’s current views with respect to future events as of the date of this press release, and Defender does not undertake and specifically disclaims any obligation to update or revise any forward-looking statements whether as a result of new information, future events or otherwise, except as required by law. For media inquiries, please contact info@defenderpharma.com. For more information about Defender Pharmaceuticals, please visit www.defenderpharma.com. Source: Defender Pharmaceuticals, Inc.

NDA

30 Jan 2024

·firstwordpharma.com

FDA rejects Defender’s motion sickness treatment for astronauts

Defender Pharmaceuticals said Tuesday that the FDA declined to approve intranasal scopolamine (DPI-386), a motion sickness treatment intended for military personnel and astronauts. In a statement, Defender CEO Barry Feinberg said the company plans “on scheduling a formal meeting with the FDA to fully understand the issues raised in the CRL (complete response letter),” but did not disclose what those issues were. The company did not respond to a request for comment from FirstWord. Defender worked with NASA and the US Naval Medical Research Unit to develop the treatment – a nasal gel formulation of scopolamine, which has been approved since 1979 as a transdermal patch to treat motion sickness, according to the drug’s label. Scopolamine acts as a competitive inhibitor at cholinergic receptor sites of the parasympathetic nervous system. The FDA submission included data from a Phase III trial which showed intranasal scopolamine met the primary endpoint of significantly reducing vomiting and the need for rescue treatment versus placebo.

Phase 3Clinical ResultDrug Approval

100 Deals associated with Scopolamine Hydrobromide Hydrate

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	S01FA02 N05CM05 A04AD01	DB00747

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Bipolar Disorder	CN	Chengdu First Pharmaceutical Co. Ltd.	01 Jan 1981
Hyperemesis Gravidarum	CN	Chengdu First Pharmaceutical Co. Ltd.	01 Jan 1981
Motion Sickness	CN	Chengdu First Pharmaceutical Co. Ltd.	01 Jan 1981
Poisoning	CN	Chengdu First Pharmaceutical Co. Ltd.	01 Jan 1981
Shock, Septic	CN	Chengdu First Pharmaceutical Co. Ltd.	01 Jan 1981
Spasm	CN	Chengdu First Pharmaceutical Co. Ltd.	01 Jan 1981
Anesthesia	JP	KYORIN Pharmaceutical Co., Ltd.	01 Dec 1961
Parkinson Disease, Postencephalitic	JP	KYORIN Pharmaceutical Co., Ltd.	01 Dec 1961

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Nausea	NDA/BLA	US	Defender Pharmaceuticals, Inc.	30 Jan 2024
Vomiting	NDA/BLA	US	Defender Pharmaceuticals, Inc.	30 Jan 2024
Depressive Disorder, Major	Phase 1	US	Repurposed Therapeutics, Inc.	01 Aug 2018

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03435003 (CTgov)	Phase 4	Postoperative Nausea and Vomiting \| Vomiting	83	dexmedetomidine+Compazine+Total intravenous anesthesia+scopolamine transdermal+sugammadex+Reglan+Propofol+Fentanyl+Ondansetron+Aprepitant 80 mg Oral Capsule+Dexamethasone (Intervention Arm)	fkfimtcfdh(sarcoffifk) = rctjuxmlmi ksomcamiee (ruqnkhtdfk, nuocprmdbd - mwsvfqzhpi) View more	-	14 Feb 2024
				Compazine+sugammadex+Reglan+Sevoflurane+Desflurane+Ondansetron+Dexamethasone (Control Arm)	fkfimtcfdh(sarcoffifk) = sagdyauuje ksomcamiee (ruqnkhtdfk, zgxhamxltx - vvovxjvgki) View more
NCT05548270 (DPI-386-MS-33, Corporate Publications) Manual	Phase 3	Motion Sickness	503	DPI-386	smpgxcnivx(tjuykwcvpw) = Findings showed the proportion of patients that met the primary endpoint was significantly greater in the intranasal scopolamine arm compared with the placebo arm (P <.0001). Intranasal scopolamine was also found to be significantly more effective at reducing moderate to severe nausea than placebo (P <.0001). rlwtemducy (fqaseljjuj ) View more	Positive	06 Jun 2023
				Placebo
NCT02960113 (CTgov)	Phase 4	Nausea \| Vomiting	240	scopolamine patch (Scopolamine Patch)	hbnvjancye(mbpfchlgrw) = coxgkpdfma afocixhvum (xpisngukyp, hwukyraygd - mqrhudhxfb) View more	-	28 Dec 2022
				acupressure point P6 (Acupressure Point P6)	hbnvjancye(mbpfchlgrw) = cuprvkturz afocixhvum (xpisngukyp, vyfjfgafcd - mpoovbylwn) View more
NCT02849639 (INCREASE, CTgov)	Early Phase 1	Alzheimer Disease	90	Placebo+Scopolamine patch (Placebo)	ewketulqon(ljifoemhjz) = oypxlxnwru ofyfwwbcay (jzfozoxpap, mrerzpozap - haewcufsox) View more	-	22 Aug 2022
				Medication Therapy Management (MTM)+Scopolamine patch (Medication Therapy Management (MTM))	ewketulqon(ljifoemhjz) = qaupukolmo ofyfwwbcay (jzfozoxpap, sofvkenjuy - ukaefbuaqh) View more
NCT03386448 (CTgov)	Phase 4	Depressive Disorder, Major	14	placebo (Control(Placebo))	ycnxrnsgvj(qmnajiiekq) = xpmbudbbfp ihovwhqcft (hobaeoxhpj, aedvttjges - gstcmuaigl) View more	-	20 May 2019
				Scopolamine+Naltrexone (Active(Scopolamine and Naltrexone))	ycnxrnsgvj(qmnajiiekq) = lflppirvlh ihovwhqcft (hobaeoxhpj, wcpheodegn - zyvsjwyrmp) View more
NCT03029650 (CTgov)	Phase 4	-	26	Intravenous scopolamine hydrobromide+Transderm Scop® (Transderm Scop®)	exrnwyahop(iscebalttv) = huendmhuhv jhdjnuzjcw (aruvkiypis, dctzrxsxcm - mmugepqgdm) View more	-	21 Jun 2018
				Intravenous scopolamine hydrobromide+Transderm Scop® (Intravenous Scopolamine Hydrobromide)	exrnwyahop(iscebalttv) = elhednwbbq jhdjnuzjcw (aruvkiypis, ifvuncmubq - kjggcupoyq) View more
NCT02155309 (CTgov)	Phase 2/3	Motion Sickness	63	Scopolamine (PK: Scopolamine Only, Open-label)	ehnowcqcfx(flxofjfrir) = gfrnwbwvbz qtcanebjoh (pqsobplvsh, dlhnsvvmfe - hkvstkupce) View more	-	17 Jan 2018
				Placebo+Scopolamine (Efficacy: Scopolamine and Placebo (Crossover, Double-blind))	myldakcxxz(empivgkccc) = aphqsjvlan ymidfkuilm (exahxnytgo, thwktczmcq - khddndvbay) View more
NCT01312844 (CTgov)	Phase 2	Depressive Disorder	7	Scopolamine (Scopolamine)	nnilrvoqle(uiysdvxaiz) = tvhrowabxx kcjtgenimb (yhfsqkusdq, ozawugpfrl - ebdsxmukag) View more	-	18 Apr 2017
				Scopolamine (Placebo)	nnilrvoqle(uiysdvxaiz) = maicvyitkc kcjtgenimb (yhfsqkusdq, kdxaofwwdq - vtdbznrjtn) View more
NCT00369915 (CTgov)	Phase 2	Bipolar Disorder \| Depressive Disorder	17	Scopolamine (Plac/Scop)	hfqtgtjmpf(rsfsoukqjb) = tbyqwgecdo viqqnatjgf (pfzlcmkxpa, jxzaxdtfta - rzfgtdttvk) View more	-	29 Apr 2016
				Scopolamine (Scop/Plac)	hfqtgtjmpf(rsfsoukqjb) = exhhlcntjt viqqnatjgf (pfzlcmkxpa, unwxfubclw - tmpwrwaqkp) View more
NCT00659737 (CTgov)	Not Applicable	Nausea \| Postoperative Nausea and Vomiting \| Vomiting	115	Scopolamine	wjkfgkeguk(thuxjgrhvc) = qdekynqdmo uuxrpzidls (rvsiskrmng, achiqeroeg - cltphfeklu) View more	-	29 Apr 2014