The WHO recommends artesunate as the drug of choice for the treatment of severe malaria. However, the efficacy of this single drug as compared to the combined drug regimen remained questionable, and the clinical response was considered delayed or inappropriate. Therefore, this research intended to evaluate the efficacy of only IV artesunate versus IV artesunate plus IV quinine in the treatment of severe malaria in children. The findings of the study would be helpful knowing whether the two drugs, when given together, have considerable benefit over single-drug therapy when given for the same.

Start Date01 Mar 2023

Sponsor / Collaborator

RESnTEC, Institute of Research

ACTRN12623000029695 / RecruitingNot ApplicableIIT

Effects of quinine, alone and combined with dietary nutrients before a highly palatable milkshake, on gut function and blood glucose in healthy volunteers

Start Date30 Jan 2023

Sponsor / Collaborator-

ACTRN12620001139965 / CompletedNot ApplicableIIT

Effects of intraduodenal administration of quinine on blood glucose concentrations, gastric emptying, gut and gluco-regulatory hormone release, and gastrointestinal symptoms in healthy females.

Start Date01 Jun 2020

Sponsor / Collaborator-

100 Clinical Results associated with Quinine Hydrochloride Hydrate

100 Translational Medicine associated with Quinine Hydrochloride Hydrate

100 Patents (Medical) associated with Quinine Hydrochloride Hydrate

8,194

Literatures (Medical) associated with Quinine Hydrochloride Hydrate

01 Jan 2025·EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

A promising class of antiprotozoal agents, design and synthesis of novel Pyrimidine–Cinnamoyl hybrids

Article

Author: Banda, Danny ; Mahlalela, Mavela ; Zininga, Tawanda ; Obakachi, Vincent A ; van Zyl, Robyn L ; Karpoormath, Rajshekhar ; Shaik, Baji Baba ; Lala, Sahil ; Kayamba, Francis ; Shonhai, Addmore ; Pooe, Ofentse J

Malaria, caused by parasitic protozoans of the Plasmodium genus, continues to be one of the greatest global health crises, especially in Africa. The emergence of antimalarial drug resistance continues to be a health problem necessitating an urgent need for alternative and cost-effective antimalarials. Using a molecular hybridization approach, we report the design and synthesis of an efficacious novel class of antiprotozoal agents; (E)-1-(4-(4,6-diphenylpyrimidin-2-yl)piperazin-1-yl)-3-phenyl prop-2-en-1-one derivatives (8a-r). The in vitro inhibitory activity of the synthesized compounds was evaluated against the NF54 chloroquine-sensitive strain of Plasmodium falciparum. From the antiprotozoal screening, three compounds displayed propitious activity with IC₅₀ values (0.18-0.21 μM), using quinine and chloroquine as standard antimalarials. Compounds 8o and 8l emerged as the most potent candidates with IC₅₀ values of 0.18 ± 0.02 μM and 0.21 ± 0.001 μM with an associated good safety index of 18.59 and 16.75 to human kidney epithelial (HEK293) cells, respectively. The synthesized analogues present a new chemical architecture structurally unrelated to the current regime of antimalarial drugs, representing a valid strategy to combat resistance in P. falciparum species to current commercial drugs. We further investigated the binding affinities of the compounds against recombinant forms of two P. falciparum heat shock protein 70 homologues; PfHsp70-1 and PfHsp70-z, both of which are essential and promising druggable candidates. Compound 8l exhibited the highest binding affinity for PfHsp70-1 and PfHsp70-z. Furthermore, molecular docking revealed that compounds 8k, 8l, 8m, and 8o exhibited better fitness to PfHsp70-1, with compounds 8l and 8o showing the highest binding affinity of -10.5 kcal/mol and -10.1 kcal/mol, respectively. Therefore, it can be speculated that PfHsp70-1 may be a possible target of some of the inhibitors tested in this study. The presence of electron-donating groups on the phenyl ring of 4,6-pyrimidine moiety and cinnamoyl group demonstrated a positive correlation between the observed computational data and the biological activity. Taken together, this paper demonstrates the importance of using the molecular hybridization approach in the development of newer cinnamoyl clubbed with 4,6-diphenyl pyrimidine hybrids as potential antiprotozoal agents.

01 Dec 2024·SLEEP MEDICINE

Signal detection of drugs associated with obstructive and central sleep apnoea

Article

Author: Joyeux-Faure, M ; Hlavaty, A ; Khouri, C. ; Jambon-Barbara, C. ; Hlavaty, A. ; Pepin, J L ; Borel, J C ; Khouri, C ; Cracowski, J.L. ; Pepin, J.L. ; Revol, B ; Cracowski, J L ; Joyeux-Faure, M. ; Revol, B. ; Borel, J.C. ; Jambon-Barbara, C

We aim to discover new safety signals of drug-induced sleep apnoea (SA), a global health problem affecting approximately 1 billion people worldwide. We first conducted a series of sequence symmetry analyses (SSA) in a cohort composed from all patients who received a first SA diagnosis or treatment between 2006 and 2018 in the Echantillon Généraliste des Bénéficaires (EGB), a random sample of the French healthcare database. We used two primary outcomes to estimate the sequence ratio (SR) for all drug classes available in France: a sensitive one (diagnosis or treatment of SA) and a specific one (Positive Airway Pressure (PAP) therapy). We then performed disproportionality analyses using the "Bayesian neural network method" on all cases of sleep apnoea (MedDRA high level term) reported up to November 2023 in the World Health Organisation (WHO) pharmacovigilance database. Among the 728,167 individuals, 46,193 had an incident diagnosis or treatment for SA and 17,080 had started an incident treatment by PAP therapy. Fifty-eight drug classes had a significant SR, with 7 considered highly plausible: opium alkaloids and derivatives, benzodiazepine derivatives, other centrally acting agents, other anxiolytics, carbamic acid esters, quinine and derivatives and antivertigo preparations; with consistent signals found for the first 3 drug classes in the disproportionality analysis. In this signal detection study, we found that opioids, benzodiazepines (but not Z-drugs) and myorelaxing agents are associated with the onset or aggravation of SA. Moreover, a new safety signal for antivertigo preparations such as betahistine emerged and needs to be further explored.

01 Dec 2024·PSYCHOPHARMACOLOGY

Corticotropin releasing hormone receptor 1 in the medial prefrontal cortex mediates aversion resistant alcohol intake

Article

Author: Beugelsdyk, Lauren A. ; Arnold, Miranda E ; Decker Ramirez, Ellie B ; Schank, Jesse R. ; Harber, Cecelia E ; Phillips, Grace B ; Decker Ramirez, Ellie B. ; Beugelsdyk, Lauren A ; Arnold, Miranda E. ; Phillips, Grace B. ; Harber, Cecelia E. ; Schank, Jesse R

RATIONALE:

Alcohol consumption despite negative consequences is a core symptom of Alcohol Use Disorder. In animal models, this is studied by pairing aversive stimuli with alcohol access, and continuation of drinking under these conditions is known as aversion resistance. Previously, we found that female mice are more aversion resistant than males. Corticotropin releasing hormone (Crh) and the Crh receptor 1 (Crhr1) regulate stress-induced reinstatement, alcohol dependence, and binge-like drinking. However, the role of the Crh system in aversion resistance has not been assessed.

OBJECTIVES:

We aimed to identify sex differences in the Crh system during quinine-adulterated alcohol intake.

METHODS:

We used two-bottle choice and adulterated the alcohol solution with quinine. Next, we measured Crh and Crhr1 levels in brain tissue using real-time polymerase chain reaction (RT-qPCR) and RNAscope in situ hybridization. We then infused a Crhr1 antagonist into the medial prefrontal cortex (mPFC) prior to quinine-alcohol intake.

RESULTS:

After quinine-alcohol consumption, females exhibited increased mPFC Crhr1 mRNA levels as measured by RT-qPCR. This was confirmed with greater anatomical specificity using RNAscope, with females exhibiting an increased number of Crhr1 + cells in the dorsomedial PFC and the ventromedial PFC. mPFC Crhr1 antagonist treatment reduced quinine-alcohol consumption in females but did not impact consumption in males. Quinine-free alcohol intake was unaffected by Crhr1 antagonist treatment.

CONCLUSIONS:

Our findings suggest that Crhr1 in mPFC plays a role in aversion resistant alcohol intake in females. Future experiments will examine the sources of Crh innervation to the mPFC and their distinct roles in alcohol seeking.

News (Medical) associated with Quinine Hydrochloride Hydrate

16 Nov 2023

·www.sciencedaily.com

New study reveals that bees cannot taste even lethal levels of pesticides

New research has revealed that bumblebees cannot taste pesticides present in nectar, even at lethal concentrations. This means bumblebees are not able to avoid contaminated nectar, putting them at high risk of pesticide exposure and posing a threat to crop pollination. New research from the University of Oxford has revealed that bumblebees cannot taste pesticides present in nectar, even at lethal concentrations. This means bumblebees are not able to avoid contaminated nectar, putting them at high risk of pesticide exposure and posing a threat to crop pollination. Bees are important pollinators of agricultural crops, but this can expose them to pesticides while they collect nectar and pollen -- some of which are very toxic to bees. Bees are known to be adept at tasting and differentiating sugary solutions. Certain toxic compounds, like quinine, taste "bitter" to bees, so the researchers sought to find out whether this sense of taste could help them avoid drinking pesticides. The researchers used two methods to test whether bumblebees (Bombus terrestris) could taste neonicotinoid and sulfoximine pesticides in nectar which mimicked that of oilseed rape (Brassica napus), and if they would avoid drinking pesticides over a very broad range of concentrations. They used electrophysiology to record the responses of neurons in taste sensilla (i.e., 'tastebuds') on bumblebee's mouthparts. This allowed them to track how often neurons 'fired' and therefore the strength of response to the taste. The researchers also tested the bumblebees' feeding behaviour by offering them either sugar solutions or pesticide-laced sugar solutions to feed on. The results demonstrated that the responses of the neurons were the same whether the bees drank sugar solution or sugar-containing pesticides. This indicates that the bumblebees' mouthparts do not have mechanisms to detect and avoid common pesticides in nectar. In the behaviour experiments, the bees consumed the same amount of food, regardless of whether the solution contained pesticides or not. This was even the case when the pesticides were present at concentrations high enough to make the bees very ill. The findings are important because they show that bumblebees cannot avoid pesticide exposure using their sense of taste. Lead author Dr Rachel Parkinson (Department of Biology, University of Oxford), said: 'As bumblebees cannot taste pesticides and don't experience immediate negative consequences from drinking them, they likely would not be able to avoid consuming nectar contaminated with pesticides in the field.' Dr Parkinson added: 'This research is important when considering the use of pesticides on outdoor crops due to the risk posed to bees as they will not avoid drinking these compounds. Potentially, these findings could be applied towards searching for a non-toxic compound that tastes bad to bees and could be used as a "bee deterrent" on pesticide-treated crops that do not require insect pollination.' Although bees did not drink less of the pesticide-laced solutions, the authors demonstrated "bitter" taste avoidance using the compound quinine. Quinine in sugar solution was deterrent to bees at high concentrations. At low concentrations, bees were observed to ingest less of the sugar solution, however the amount of time they spent in contact with the feeding solution was the same. *The pesticides used in the study were the neonicotinoids imidacloprid, thiamethoxam, clothianidin and the sulfoximine pesticide sulfoxaflor.

Clinical Result

10 Jul 2023

·www.sciencedaily.com

Bees make decisions better and faster than we do, for the things that matter to them

Research reveals how millions of years of evolution has engineered honey bees to make fast decisions and reduce risk. Honey bees have to balance effort, risk and reward, making rapid and accurate assessments of which flowers are mostly likely to offer food for their hive. Research published in the journal eLife today reveals how millions of years of evolution has engineered honey bees to make fast decisions and reduce risk. The study enhances our understanding of insect brains, how our own brains evolved, and how to design better robots. The paper presents a model of decision-making in bees and outlines the paths in their brains that enable fast decision-making. The study was led by Professor Andrew Barron from Macquarie University in Sydney, and Dr HaDi MaBouDi, Neville Dearden and Professor James Marshall from the University of Sheffield. "Decision-making is at the core of cognition," says Professor Barron. "It's the result of an evaluation of possible outcomes, and animal lives are full of decisions. A honey bee has a brain smaller than a sesame seed. And yet she can make decisions faster and more accurately than we can. A robot programmed to do a bee's job would need the back up of a supercomputer. "Today's autonomous robots largely work with the support of remote computing," Professor Barron continues. "Drones are relatively brainless, they have to be in wireless communication with a data centre. This technology path will never allow a drone to truly explore Mars solo -- NASA's amazing rovers on Mars have travelled about 75 kilometres in years of exploration." Bees need to work quickly and efficiently, finding nectar and returning it to the hive, while avoiding predators. They need to make decisions. Which flower will have nectar? While they're flying, they're only prone to aerial attack. When they land to feed, they're vulnerable to spiders and other predators, some of which use camouflage to look like flowers. "We trained 20 bees to recognise five different coloured 'flower disks'. Blue flowers always had sugar syrup," says Dr MaBouDi. "Green flowers always had quinine [tonic water] with a bitter taste for bees. Other colours sometimes had glucose." "Then we introduced each bee to a 'garden' where the 'flowers' just had distilled water. We filmed each bee then watched more than 40 hours of video, tracking the path of the bees and timing how long it took them to make a decision. "If the bees were confident that a flower would have food, then they quickly decided to land on it taking an average of 0.6 seconds)," says Dr MaBouDi. "If they were confident that a flower would not have food, they made a decision just as quickly." If they were unsure, then they took much more time -- on average 1.4 seconds -- and the time reflected the probability that a flower had food. The team then built a computer model from first principles aiming to replicate the bees' decision-making process. They found the structure of their computer model looked very similar to the physical layout of a bee brain. "Our study has demonstrated complex autonomous decision-making with minimal neural circuitry," says Professor Marshall. "Now we know how bees make such smart decisions, we are studying how they are so fast at gathering and sampling information. We think bees are using their flight movements to enhance their visual system to make them better at detecting the best flowers." AI researchers can learn much from insects and other 'simple' animals. Millions of years of evolution has led to incredibly efficient brains with very low power requirements. The future of AI in industry will be inspired by biology, says Professor Marshall, who co-founded Opteran, a company that reverse-engineers insect brain algorithms to enable machines to move autonomously, like nature.

26 Apr 2023

·www.biospace.com

Fosun Pharma Develops Innovative Artemisinin-based Antimalarial Drugs Contributing to the Efforts for A Malaria-free World Through the Belt and Road Initiative

SHANGHAI, April 26, 2023 /PRNewswire/ -- On April 25, 2023, World Health Organization (WHO) gave as the theme for World Malaria Day 2023 Time to deliver zero malaria: invest, innovate, implement. Within this theme, WHO will mainly focus on the third "i" – implement – and notably the critical importance of reaching hard to reach populations with the tools and strategies that are available today. This year 2023 also marks the 10th anniversary of the Belt and Road Initiative. Medicine knows no borders. Artemisinin and its derivatives have moved from the countries along the Belt and Road to the forefront of the world's battle against malaria since it was discovered by Chinese scientists, more than 50 years ago. Through continuous innovation and global operation, Fosun Pharma has implemented and extended its efforts to "Helping Africa Fight Malaria" and contributed to the implementation of the "Belt and Road Initiative" building a community with a shared positive future for mankind. By the end of 2022, Artesun (Artesunate for Injection), independently developed and manufactured by Fosun Pharma, had treated over 56 million patients with severe malaria worldwide, becoming a prime example for innovative medicinal products developed in China serving the world. Chinese wisdom and solutions contribute to the global anti-malarial fight and to build a better future through the "Belt and Road Initiative" As one of the oldest and most widely spreading infectious diseases in the world, malaria continues to have a devastating impact on human health around the world. Historically, malaria was also widespread in China. In the 1970s, a profound effort by researchers in China as a potent antimalarial drug, inspired by ancient traditional Chinese medicine books. Subsequent development, clinical trials and deployment of this new class of drugs was essential for, malaria prevention and control in China, accumulating after more than 70 years of unremitting efforts, certification by the WHO of "Malaria-free" in 2021. From 30 million cases of the disease annually to zero, China's tireless effort to achieve this important milestone in the fight against malaria demonstrates the persistence, efforts and dedication of the Chinese people of several generations of Chinese people. However, the global efforts to control and eliminate malaria remain challenging: whereas some countries have importantly reduced their malaria burden or even eliminated malaria; others countries have seen an increase in the number of malaria patients. There were an estimated 619,000 deaths due to malaria in 2021 according to the World Malaria Report 2022 released in December 2022. The WHO African Region carries a disproportionately high share of the global malaria burden. In 2021, the Region was home to 95% of malaria cases (234 million) and 96% of malaria deaths (593,000). Children under five years old accounted for about 80% of all malaria deaths in the Region. To truly win the fight against malaria, malaria must be eradicated globally! Over the past decade of the Belt and Road Initiative, China's products for malaria prevention and control, as well as China's approach to malaria elimination, have been closely observed and are widely recognized by the WHO and the international malaria community. China's experience continues to contribute to malaria control and elimination in developing countries. The story of China's participation in global malaria elimination extends the purpose of the Silk Road and it aims to create a better future through the "Belt and Road Initiative". From the discovery of artemisinin by Tu Youyou to the wide application of artesunate for injection, an innovative drug developed in China, Chinese wisdom, and approaches contribute to the global fight against malaria. Fosun Pharma continues its independent R&D of innovative antimalarial drugs used for malaria prevention, treatment of uncomplicated malaria and life-saving treatment of severe malaria patients In 1987, Guilin Pharma, a Fosun Pharma subsidiary, was authorized the China No. X-01 Class I New Drug Certificate by the Ministry of Health of the PRC for its independently researched and developed artesunate, and the No. X-02 New Drug Certificate for artesunate for injection. Since then, artesunate has been widely used for the treatment of malaria globally, saving countless lives of malaria patients. In 2000, it was listed as one of the essential antimalarial drugs by the World Health Organization. In early 2011, the World Health Organization revised the Guidelines for the Treatment of Malaria by changing the first-line drug for treating severe malaria from quinine to injectable artesunate. By the end of 2022, Fosun Pharma had supplied more than 280 million doses of Artesun (artesunate for injection) to the world, treating more than 56 million severe malaria patients worldwide. Fosun Pharma continues its independent R&D of innovative antimalarial drugs used for malaria prevention, malaria treatment and life-saving treatment of severe malaria patients. Ranging from malaria treatment to prevention, Fosun Pharma continues to provide solutions, in particular also for children, helping to effectively reduce the malaria burden and death toll of malaria in children under five years old in Africa. In August 2018, Fosun Pharma's SPAQ-CO® Disp (co-packed sulfadoxine-pyrimethamine dispersible tablets and amodiaquine dispersible tablets), for the prevention of malaria in children, was pre-qualified by WHO (WHO-PQ). By the end of 2022, around 210 million children in Africa have benefited from the "Seasonal Malaria Chemoprevention Program", for which SPAQ-CO® Disp is used as the core drug and which has effectively reduced the morbidity of malaria in children under five years old in Africa. Continuously improve global operation capability and fulfill corporate social responsibility Since 2006, Fosun Pharma has actively participated in the Chinese government's Assistance to Africa in Fighting Malaria and has also participated in various public welfare activities and international malaria research projects aiming to help improve malaria control capacity in Africa. Fosun Pharma has been a core supplier of antimalarial drugs to the Global Fund, UNICEF, WHO, and national drug procurement centers in Africa. In recent years, Fosun Pharma has continuously improved its global operating capacity. By the end of 2022, a revenue of RMB 13.938 billion was earned in regions outside Chinese Mainland and other countries, accounting for 31.7% of its total revenue 2022. After more than 15 years of operations in Africa, Fosun Pharma has established a sales and marketing network in 39 countries and regions in Africa, ensuring the continued availability of medicines and healthcare products in Africa, including antimalarial drugs. Moreover, Fosun Pharma has set up five regional distribution centers in emerging markets such as Africa, with a first-line commercialization team of approximately 800 people. Among them, the Côte d'Ivoire distribution center in West Africa was officially opened in 2021 and is currently the largest local drug distribution center in the francophone region of West Africa. In November 2022, Fosun Pharma's Côte d'Ivoire campus project was officially launched, marking an important step for Fosun Pharma in the realization of local drug manufacturing and supply in Africa. In the future, the antimalarials and antibiotics produced by Fosun Pharma's Côte d'Ivoire factory will be distributed through its holding subsidiary Tridem Pharma to help Côte d'Ivoire and other regions in West Africa realize the local supply of essential drugs, thus reducing the risk of drug shortage, important for instance in case of public health crises requiring an emergency response. Wen Deyong, CEO of Fosun Pharma, said, "As a global innovation-driven pharmaceutical and healthcare industry group, Fosun Pharma always regards innovation as the most important social responsibility for a pharmaceutical enterprise. Up to now, Fosun Pharma has 30 antimalarial drugs prequalified by WHO, ranking first in the world. Meanwhile, Fosun Pharma's global operational networks will further improve the availability and affordability of antimalarial medicines so as to contribute to the achievement of the goal to end malaria by 2030." About Fosun Pharma Founded in 1994, Shanghai Fosun Pharmaceutical (Group) Co., Ltd.* ("Fosun Pharma"; stock code: 600196. SH, 02196. HK) is a global innovation-driven pharmaceutical and healthcare industry group. Fosun Pharma directly operates businesses including pharmaceuticals, medical devices, medical diagnosis, and healthcare services. As a shareholder of Sinopharm Co., Ltd., Fosun Pharma expands its areas in the pharmaceutical distribution and retail business. Fosun Pharma is patient-centered and clinical needs-oriented. The company continuously enriches its innovative product pipeline through independent research and development, cooperative development, license-in, and in-depth incubation. Fosun Pharma improves the research and clinical development capabilities of FIC (First-in-class) and BIC (Best-in-class) new drugs as well as accelerates the R&D and launch of innovative technologies and products. Guided by the 4IN strategy (Innovation, Internationalization, Intelligentization, and Integration), Fosun Pharma will uphold the development model of "Innovation Transformation, Integrated Operation and Steady Growth", with the mission of creating shareholder values through strengthening its independent R&D and external cooperation and enriching its product pipelines, as well as promoting the global networks and enhancing operational efficiency. Fosun Pharma will actively promote the digital and physical business layout in the pharmaceutical and healthcare industry and is committed to becoming a first-class enterprise in the global medical and health market. For more information, please visit our official website: View original content to download multimedia: SOURCE Fosun Pharma Company Codes: HongKong:2196, Shanghai:600196

Drug Approval

100 Deals associated with Quinine Hydrochloride Hydrate

External Link

KEGG	Wiki	ATC	Drug Bank
D02261	-	P01BC01	DB00468

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Malaria	JP	Mylan Pharmaceuticals ULC	01 Dec 1953

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ISRCTN99046537 (Pubmed \| PLoS One)	Not Applicable	Malaria	220	Quinine	suebpxrvso(qqhzkhdqpj) = tended to be lower in the DHAPQ (1%, 1/72) than in the quinine (7%, 8/110) or AL (6%, 2/35) group, though it was not statistically significant yjylnwtlki (wonntjgkxs )	-	01 Jan 2013
				Artemether-lumefantrine (AL)
NCT00495508 (Pubmed \| Lancet Infect Dis)	Phase 4	Malaria, Falciparum	304	Artemether-lumefantrine	erookxelxn(sputvufpgy) = kbtkitmkfq mrkxixagjm (rscbelsfmd )	Positive	01 Nov 2010
				Quinine hydrochloride	erookxelxn(sputvufpgy) = eaxouflwdc mrkxixagjm (rscbelsfmd )
SFN2001	Not Applicable	-	-	Quinine	jwwfwmrhdq(jgatbiahmn) = ggsizfgwul hqkolnzdgb (udlbkjfwam )	-	14 Nov 2001
				Quaternary derivative of quinine	jwwfwmrhdq(jgatbiahmn) = alfghcvyqh hqkolnzdgb (udlbkjfwam )

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