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The Journal of Clinical Endocrinology... Jun 2022The bitter substance quinine modulates the release of a number of gut and gluco-regulatory hormones and upper gut motility. As the density of bitter receptors may be... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
The bitter substance quinine modulates the release of a number of gut and gluco-regulatory hormones and upper gut motility. As the density of bitter receptors may be higher in the duodenum than the stomach, direct delivery to the duodenum may be more potent in stimulating these functions. The gastrointestinal responses to bitter compounds may also be modified by sex.
BACKGROUND
We have characterized the effects of intragastric (IG) versus intraduodenal (ID) administration of quinine hydrochloride (QHCl) on gut and pancreatic hormones and antropyloroduodenal pressures in healthy men and women.
METHODS
14 men (26 ± 2 years, BMI: 22.2 ± 0.5 kg/m2) and 14 women (28 ± 2 years, BMI: 22.5 ± 0.5 kg/m2) received 600 mg QHCl on 2 separate occasions, IG or ID as a 10-mL bolus, in randomized, double-blind fashion. Plasma ghrelin, cholecystokinin, peptide YY, glucagon-like peptide-1 (GLP-1), insulin, glucagon, and glucose concentrations and antropyloroduodenal pressures were measured at baseline and for 120 minutes following QHCl.
RESULTS
Suppression of ghrelin (P = 0.006), stimulation of cholecystokinin (P = 0.030), peptide YY (P = 0.017), GLP-1 (P = 0.034), insulin (P = 0.024), glucagon (P = 0.030), and pyloric pressures (P = 0.050), and lowering of glucose (P = 0.001) were greater after ID-QHCl than IG-QHCl. Insulin stimulation (P = 0.021) and glucose reduction (P = 0.001) were greater in females than males, while no sex-associated effects were found for cholecystokinin, peptide YY, GLP-1, glucagon, or pyloric pressures.
CONCLUSION
ID quinine has greater effects on plasma gut and pancreatic hormones and pyloric pressures than IG quinine in healthy subjects, consistent with the concept that stimulation of small intestinal bitter receptors is critical to these responses. Both insulin stimulation and glucose lowering were sex-dependent.
Topics: Cholecystokinin; Double-Blind Method; Energy Intake; Female; Gastrointestinal Motility; Ghrelin; Glucagon; Glucagon-Like Peptide 1; Glucose; Humans; Insulin; Male; Pancreatic Hormones; Peptide YY; Quinine
PubMed: 35325161
DOI: 10.1210/clinem/dgac182 -
The Cochrane Database of Systematic... Apr 2015Muscle cramps can occur anywhere and for many reasons. Quinine has been used to treat cramps of all causes. However, controversy continues about its efficacy and safety.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Muscle cramps can occur anywhere and for many reasons. Quinine has been used to treat cramps of all causes. However, controversy continues about its efficacy and safety. This review was first published in 2010 and searches were updated in 2014.
OBJECTIVES
To assess the efficacy and safety of quinine-based agents in treating muscle cramps.
SEARCH METHODS
On 27 October 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE and EMBASE. We searched reference lists of articles up to 2014. We also searched for ongoing trials in November 2014.
SELECTION CRITERIA
Randomised controlled trials of people of all ages with muscle cramps in any location and of any cause, treated with quinine or its derivatives.
DATA COLLECTION AND ANALYSIS
Three review authors independently selected trials for inclusion, assessed risk of bias and extracted data. We contacted study authors for additional information. For comparisons including more than one trial, we assessed the quality of the evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE).
MAIN RESULTS
We identified 23 trials with a total of 1586 participants. Fifty-eight per cent of these participants were from five unpublished studies. Quinine was compared to placebo (20 trials, n = 1140), vitamin E (four trials, n = 543), a quinine-vitamin E combination (three trials, n = 510), a quinine-theophylline combination (one trial, n = 77), and xylocaine injections into the gastrocnemius muscle (one trial, n = 24). The most commonly used quinine dosage was 300 mg/day (range 200 to 500 mg). We found no new trials for inclusion when searches were updated in 2014.The risk of bias in the trials varied considerably. All 23 trials claimed to be randomised, but only a minority described randomisation and allocation concealment adequately.Compared to placebo, quinine significantly reduced cramp number over two weeks by 28%, cramp intensity by 10%, and cramp days by 20%. Cramp duration was not significantly affected.A significantly greater number of people suffered minor adverse events on quinine than placebo (risk difference (RD) 3%, 95% confidence interval (CI) 0% to 6%), mainly gastrointestinal symptoms. Overdoses of quinine have been reported elsewhere to cause potentially fatal adverse effects, but in the included trials there was no significant difference in major adverse events compared with placebo (RD 0%, 95% CI -1% to 2%). One participant suffered from thrombocytopenia (0.12% risk) on quinine.A quinine-vitamin E combination, vitamin E alone, and xylocaine injections into gastrocnemius were not significantly different to quinine across all outcomes, including adverse effects. Based on a single trial comparison, quinine alone was significantly less effective than a quinine-theophylline combination but with no significant differences in adverse events.
AUTHORS' CONCLUSIONS
There is low quality evidence that quinine (200 mg to 500 mg daily) significantly reduces cramp number and cramp days and moderate quality evidence that quinine reduces cramp intensity. There is moderate quality evidence that with use up to 60 days, the incidence of serious adverse events is not significantly greater than for placebo in the identified trials, but because serious adverse events can be rarely fatal, in some countries prescription of quinine is severely restricted.Evidence from single trials suggests that theophylline combined with quinine improves cramps more than quinine alone, and the effects of xylocaine injections into gastrocnemius are not significantly different to quinine across all outcomes. Low or moderate quality evidence shows no significant difference between quinine and vitamin E or quinine and quinine-vitamin E mixture. Further research into these alternatives, as well other pharmacological and non-pharmacological treatments, is thus warranted.There is no evidence to judge optimal dosage or duration of quinine treatment. Further studies using different dosages and measurement of serum quinine levels will allow a therapeutic range to be defined for muscle cramp. Because serious adverse events are not common, large population studies are required to more accurately inform incidence. Longer lengths of follow-up in future trials will help determine the duration of action following cessation of quinine as well as long-term adverse events. The search for new therapies, pharmacological and nonpharmacological, should continue and further trials should compare vitamin E, quinine-vitamin E combination, and quinine-theophylline mixture with quinine.
Topics: Drug Therapy, Combination; Humans; Lidocaine; Muscle Cramp; Muscle Relaxants, Central; Quinine; Randomized Controlled Trials as Topic; Theophylline; Vitamin E; Vitamins
PubMed: 25842375
DOI: 10.1002/14651858.CD005044.pub3 -
Asian Pacific Journal of Cancer... Dec 2022Angiogenesis is the process of vascularization from preexisting blood vessels. It is essential for many physiological and pathological processes. Quinine is an...
BACKGROUND
Angiogenesis is the process of vascularization from preexisting blood vessels. It is essential for many physiological and pathological processes. Quinine is an anti-malarial agent belongs to the quinoline alkaloid that can inhibit angiogenesis. Vitamin C is also an important antioxidant and has been shown to reduce angiogenesis in tumor.
OBJECTIVE
The study was aimed at investigating the effect of quinine alone and in combination with vitamin C on angiogenesis process.
MATERIALS AND METHODS
12 to 14 weeks old male albino rats were used for the study. Quinine was prepared by dissolving in DMSO and was serially diluted. The rat aorta ring assay was employed to investigate the antiangiogenic effect of quinine ex vivo. An in vivo chorioallantoic membrane (CAM) assay was used to measure the blood vessels inhibition zone by quinine. The zone of inhibition was calculated as the mean inhibition area of a blood vessel in mm±SD.The obtained data were statistically analyzed.
RESULTS
The results revealed that quinine has a significant dose-dependent inhibition effect on the growth of blood vessels by 98% ± 0.07 in concentration 100µg/ml when compared to the negative control. moreover, the inhibition of blood vessels growth as a measure of the antiangiogenic activity of quinine in combination with vitamin C shows a synergistic effect when the concentration that inhibit 50% of blood vessels growth (IC50) which equals to 5.05 µg/ml resulted in 85% of growth inhibition when combined with IC50 of vitamin C which equals to 22..87µg/ml.
CONCLUSION
The findings suggest that the activity of quinine with vitamin C synergism can greatly lower blood vessels growth in rat aorta rings and CAM assays. Quininehas an inhibitory effect on tumor and can be utilized as an antiangiogenic agent alone or in combination with vitamin C.
Topics: Animals; Male; Angiogenesis Inhibitors; Ascorbic Acid; Chorioallantoic Membrane; Neoplasms; Neovascularization, Pathologic; Quinine; Vitamins; Rats
PubMed: 36580001
DOI: 10.31557/APJCP.2022.23.12.4185 -
CMAJ : Canadian Medical Association... Jul 2015
Topics: Female; Humans; Internet; Male; Muscle Relaxants, Central; Quinine; Seasons; Sleep-Wake Transition Disorders
PubMed: 26170462
DOI: 10.1503/cmaj.1150040 -
CMAJ : Canadian Medical Association... Jul 2015
Topics: Female; Humans; Internet; Male; Muscle Relaxants, Central; Quinine; Seasons; Sleep-Wake Transition Disorders
PubMed: 26170461
DOI: 10.1503/cmaj.1150039 -
The American Journal of Tropical... Aug 2016Quinine, a bitter-tasting, short-acting alkaloid drug extracted from cinchona bark, was the first drug used widely for malaria chemoprophylaxis from the 19th century.... (Review)
Review
Quinine, a bitter-tasting, short-acting alkaloid drug extracted from cinchona bark, was the first drug used widely for malaria chemoprophylaxis from the 19th century. Compliance was difficult to enforce even in organized groups such as the military, and its prophylaxis potential was often questioned. Severe adverse events such as blackwater fever occurred rarely, but its relationship to quinine remains uncertain. Quinine prophylaxis was often counterproductive from a public health viewpoint as it left large numbers of persons with suppressed infections producing gametocytes infective for mosquitoes. Quinine was supplied by the first global pharmaceutical cartel which discouraged competition resulting in a near monopoly of cinchona plantations on the island of Java which were closed to Allied use when the Japanese Imperial Army captured Indonesia in 1942. The problems with quinine as a chemoprophylactic drug illustrate the difficulties with medications used for prevention and the acute need for improved compounds.
Topics: Africa; Antimalarials; Asia; Australia; Blackwater Fever; Chemoprevention; Cinchona; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Malaria, Falciparum; Plasmodium falciparum; Quinine
PubMed: 27185766
DOI: 10.4269/ajtmh.16-0138 -
The Journal of the Royal College of... Mar 2023Quinine has been used in Western medicine since the 16th century, and far longer in South America. It has gained an undeserved reputation as an effective treatment for...
Quinine has been used in Western medicine since the 16th century, and far longer in South America. It has gained an undeserved reputation as an effective treatment for leg cramps and continues to be widely used in the United Kingdom and elsewhere despite warnings from the Medicines and Healthcare products Regulatory Agency (MHRA) and the US Food and Drug Administration (FDA). The effects in overdose are outlined and a personal perspective of scientific investigation of treatments at one time advocated provided.
Topics: United States; Humans; Quinine; Muscle Cramp; United Kingdom
PubMed: 36703282
DOI: 10.1177/14782715231152681 -
Organic Letters Mar 2021The enzymatic basis for quinine biosynthesis was investigated. Transcriptomic data from the producing plant led to the discovery of three enzymes involved in the early...
The enzymatic basis for quinine biosynthesis was investigated. Transcriptomic data from the producing plant led to the discovery of three enzymes involved in the early and late steps of the pathway. A medium-chain alcohol dehydrogenase (CpDCS) and an esterase (CpDCE) yielded the biosynthetic intermediate dihydrocorynantheal from strictosidine aglycone . Additionally, the discovery of an -methyltransferase specific for 6'-hydroxycinchoninone suggested the final step order to be cinchoninone hydroxylation, methylation, and keto-reduction.
Topics: Hydroxylation; Methyltransferases; Molecular Structure; Quinine; Vinca Alkaloids
PubMed: 33625237
DOI: 10.1021/acs.orglett.1c00206 -
Revista Espanola de Quimioterapia :... Sep 2016Malaria is one of the most widespread infectious diseases around the world with 214 million cases and 438,000 deaths in 2015. In the early twentieth century it was... (Review)
Review
Malaria is one of the most widespread infectious diseases around the world with 214 million cases and 438,000 deaths in 2015. In the early twentieth century it was described for the first time the resistance to quinine and, since then, drug resistance to antimalarial drugs has spread up to represent a global challenge in the fight and control of malaria. Understanding the mechanisms, geography and monitoring tools that we can act against resistance to antimalarial drugs is critical to prevent its expansion.
Topics: Antimalarials; Drug Resistance; Humans; Malaria; Plasmodium; Quinine
PubMed: 27608319
DOI: No ID Found -
Alcohol (Fayetteville, N.Y.) May 2014Continued seeking and drinking of alcohol despite adverse legal, health, economic, and societal consequences is a central hallmark of human alcohol use disorders. This... (Review)
Review
Continued seeking and drinking of alcohol despite adverse legal, health, economic, and societal consequences is a central hallmark of human alcohol use disorders. This compulsive drive for alcohol, defined by resistance to adverse and deleterious consequences, represents a major challenge when attempting to treat alcoholism clinically. Thus, there has long been interest in developing pre-clinical rodent models for the compulsive drug use that characterizes drug addiction. Here, we review recent studies that have attempted to model compulsive aspects of alcohol and cocaine intake in rodents, and consider technical and conceptual issues that need to be addressed when trying to recapitulate compulsive aspects of human addiction. Aversion-resistant alcohol intake has been examined by pairing intake or seeking with the bitter tastant quinine or with footshock, and exciting recent work has used these models to identify neuroadaptations in the amygdala, cortex, and striatal regions that promote compulsive intake. Thus, rodent models do seem to reflect important aspects of compulsive drives that sustain human addiction, and will likely provide critical insights into the molecular and circuit underpinnings of aversion-resistant intake as well as novel therapeutic interventions for compulsive aspects of addiction.
Topics: Alcohol Drinking; Amygdala; Animals; Compulsive Behavior; Corpus Striatum; Female; Male; Mice; Models, Animal; Quinine; Rats; Taste
PubMed: 24731992
DOI: 10.1016/j.alcohol.2014.03.001