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Article: Emetine, Ipecac, Ipecac Alkaloids and Analogues as Potential Antiviral Agents for Coronaviruses.

Bleasel, Martin D / Peterson, Gregory M

2020 Volume 13, Issue 3

Abstract: The COVID-19 coronavirus is currently spreading around the globe with limited treatment options available. This article presents the rationale for potentially using old drugs (emetine, other ipecac alkaloids or analogues) that have been used to treat ... ...

Abstract	The COVID-19 coronavirus is currently spreading around the globe with limited treatment options available. This article presents the rationale for potentially using old drugs (emetine, other ipecac alkaloids or analogues) that have been used to treat amoebiasis in the treatment of COVID-19. Emetine had amongst the lowest reported half-maximal effective concentration (EC
Keywords	covid19
Language	English
Publishing date	2020-03-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph13030051
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Emetine Is Not Ipecac: Considerations for Its Use as Treatment for SARS-CoV2.

Bleasel, Martin D / Peterson, Gregory M

Pharmaceuticals (Basel, Switzerland)

2020 Volume 13, Issue 12

Abstract: Emetine is a potent antiviral that acts on many viruses in the low-nM range, with several studies in animals and humans demonstrating antiviral activity. Historically, emetine was used to treat patients with Spanish influenza, in the last stages of the ... ...

Abstract	Emetine is a potent antiviral that acts on many viruses in the low-nM range, with several studies in animals and humans demonstrating antiviral activity. Historically, emetine was used to treat patients with Spanish influenza, in the last stages of the pandemic in the early 1900s. Some of these patients were "black" with cyanosis. Emetine rapidly reversed the cyanosis and other symptoms of this disease in 12-24 h. However, emetine also has been shown to have anti-inflammatory properties and it appears it is these anti-inflammatory properties that were responsible for the effects seen in patients with Spanish influenza. Emetine, in the past, has also been used in 10s to 100s of millions of people at a dose of ~60 mg daily to treat amoebiasis. Based on viral inhibition data we can calculate a likely SARS-CoV2 antiviral dose of ~1/10th the amoebiasis dose, which should dramatically reduce the risk of any side effects. While there are no anti-inflammatory dose response data available, based on the potential mode of action, the anti-inflammatory actions may also occur at low doses. This paper also examines the toxicity of emetine seen in clinical practice and that seen in the laboratory, and discusses the methods of administration aimed at reducing side effects if higher doses were found to be necessary. While emetine is a "pure drug" as it is extracted from ipecac, some of the differences between emetine and ipecac are also discussed.
Language	English
Publishing date	2020-11-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph13120428
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Emetine, Ipecac, Ipecac Alkaloids and Analogues as Potential Antiviral Agents for Coronaviruses

Bleasel, Martin D / Peterson, Gregory M

Abstract	The COVID-19 coronavirus is currently spreading around the globe with limited treatment options available. This article presents the rationale for potentially using old drugs (emetine, other ipecac alkaloids or analogues) that have been used to treat amoebiasis in the treatment of COVID-19. Emetine had amongst the lowest reported half-maximal effective concentration (EC50) from over 290 agents screened for the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) coronaviruses. While EC50 concentrations of emetine are achievable in the blood, studies show that concentrations of emetine can be almost 300 times higher in the lungs. Furthermore, based on the relative EC50s of emetine towards the coronaviruses compared with Entamoeba histolytica, emetine could be much more effective as an anti-coronavirus agent than it is against amoebiasis. This paper also discusses the known side effects of emetine and related compounds, how those side effects can be managed, and the optimal method of administration for the potential treatment of COVID-19. Given the serious and immediate threat that the COVID-19 coronavirus poses, our long history with emetine and the likely ability of emetine to reach therapeutic concentrations within the lungs, ipecac, emetine, and other analogues should be considered as potential treatment options, especially if in vitro studies confirm viral sensitivity.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: ##BR#"11548
Database	COVID19

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Article ; Online: Emetine, Ipecac, Ipecac Alkaloids and Analogues as Potential Antiviral Agents for Coronaviruses

Bleasel, Martin D. / Peterson, Gregory

Pharmaceuticals, 13(3):51

2020

Abstract	The COVID-19 coronavirus is currently spreading around the globe with limited treatment options available. This article presents the rationale for potentially using old drugs (emetine, other ipecac alkaloids or analogues) that have been used to treat amoebiasis in the treatment of COVID-19. Emetine had amongst the lowest reported half-maximal effective concentration (EC50) from over 290 agents screened for the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) coronaviruses. While EC50 concentrations of emetine are achievable in the blood, studies show that concentrations of emetine can be almost 300 times higher in the lungs. Furthermore, based on the relative EC50s of emetine towards the coronaviruses compared with Entamoeba histolytica, emetine could be much more effective as an anti-coronavirus agent than it is against amoebiasis. This paper also discusses the known side effects of emetine and related compounds, how those side effects can be managed, and the optimal method of administration for the potential treatment of COVID-19. Given the serious and immediate threat that the COVID-19 coronavirus poses, our long history with emetine and the likely ability of emetine to reach therapeutic concentrations within the lungs, ipecac, emetine, and other analogues should be considered as potential treatment options, especially if in vitro studies confirm viral sensitivity.
Keywords	COVID-19 ; emetine ; repurposing: antiviral ; ipecac ; MERS ; treatment ; SARS ; Coronavirus ; dehydroemetine ; covid19
Language	English
Publishing country	de
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: Emetine, Ipecac, Ipecac Alkaloids and Analogues as Potential Antiviral Agents for Coronaviruses

Martin D Bleasel / Gregory M Peterson

Pharmaceuticals ; Volume 13 ; Issue 3

2020

Abstract	The COVID-19 coronavirus is currently spreading around the globe with limited treatment options available. This article presents the rationale for potentially using old drugs (emetine, other ipecac alkaloids or analogues) that have been used to treat amoebiasis in the treatment of COVID-19. Emetine had amongst the lowest reported half-maximal effective concentration (EC50) from over 290 agents screened for the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) coronaviruses. While EC50 concentrations of emetine are achievable in the blood, studies show that concentrations of emetine can be almost 300 times higher in the lungs. Furthermore, based on the relative EC50s of emetine towards the coronaviruses compared with Entamoeba histolytica, emetine could be much more effective as an anti-coronavirus agent than it is against amoebiasis. This paper also discusses the known side effects of emetine and related compounds, how those side effects can be managed, and the optimal method of administration for the potential treatment of COVID-19. Given the serious and immediate threat that the COVID-19 coronavirus poses, our long history with emetine and the likely ability of emetine to reach therapeutic concentrations within the lungs, ipecac, emetine, and other analogues should be considered as potential treatment options, especially if in vitro studies confirm viral sensitivity.
Keywords	COVID-19 ; coronavirus ; emetine ; ipecac ; dehydroemetine ; MERS ; SARS ; treatment ; repurposing: antiviral ; covid19
Language	English
Publishing date	2020-03-21
Publisher	Multidisciplinary Digital Publishing Institute
Publishing country	ch
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Emetine, Ipecac, Ipecac Alkaloids and Analogues as Potential Antiviral Agents for Coronaviruses

Martin D. Bleasel / Gregory M. Peterson

Pharmaceuticals, Vol 13, Iss 3, p

2020 Volume 51

Abstract	The COVID-19 coronavirus is currently spreading around the globe with limited treatment options available. This article presents the rationale for potentially using old drugs (emetine, other ipecac alkaloids or analogues) that have been used to treat amoebiasis in the treatment of COVID-19. Emetine had amongst the lowest reported half-maximal effective concentration (EC 50 ) from over 290 agents screened for the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) coronaviruses. While EC 50 concentrations of emetine are achievable in the blood, studies show that concentrations of emetine can be almost 300 times higher in the lungs. Furthermore, based on the relative EC 50 s of emetine towards the coronaviruses compared with Entamoeba histolytica , emetine could be much more effective as an anti-coronavirus agent than it is against amoebiasis. This paper also discusses the known side effects of emetine and related compounds, how those side effects can be managed, and the optimal method of administration for the potential treatment of COVID-19. Given the serious and immediate threat that the COVID-19 coronavirus poses, our long history with emetine and the likely ability of emetine to reach therapeutic concentrations within the lungs, ipecac, emetine, and other analogues should be considered as potential treatment options, especially if in vitro studies confirm viral sensitivity.
Keywords	covid-19 ; coronavirus ; emetine ; ipecac ; dehydroemetine ; mers ; sars ; treatment ; repurposing: antiviral ; Medicine ; R ; Pharmacy and materia medica ; RS1-441 ; covid19
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Emetine Is Not Ipecac

Martin D. Bleasel / Gregory M. Peterson

Pharmaceuticals, Vol 13, Iss 428, p

Considerations for Its Use as Treatment for SARS-CoV2

2020 Volume 428

Abstract	Emetine is a potent antiviral that acts on many viruses in the low-nM range, with several studies in animals and humans demonstrating antiviral activity. Historically, emetine was used to treat patients with Spanish influenza, in the last stages of the pandemic in the early 1900s. Some of these patients were “black” with cyanosis. Emetine rapidly reversed the cyanosis and other symptoms of this disease in 12–24 h. However, emetine also has been shown to have anti-inflammatory properties and it appears it is these anti-inflammatory properties that were responsible for the effects seen in patients with Spanish influenza. Emetine, in the past, has also been used in 10s to 100s of millions of people at a dose of ~60 mg daily to treat amoebiasis. Based on viral inhibition data we can calculate a likely SARS-CoV2 antiviral dose of ~1/10th the amoebiasis dose, which should dramatically reduce the risk of any side effects. While there are no anti-inflammatory dose response data available, based on the potential mode of action, the anti-inflammatory actions may also occur at low doses. This paper also examines the toxicity of emetine seen in clinical practice and that seen in the laboratory, and discusses the methods of administration aimed at reducing side effects if higher doses were found to be necessary. While emetine is a “pure drug” as it is extracted from ipecac, some of the differences between emetine and ipecac are also discussed.
Keywords	COVID-19 ; coronavirus ; emetine ; ipecac ; dehydroemetine ; treatment ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
Subject code	610
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Asperuloside Enhances Taste Perception and Prevents Weight Gain in High-Fat Fed Mice.

Ishaq, Muhammad / Tran, Duyen / Wu, Yijia / Nowak, Krzysztof / Deans, Bianca J / Xin, Joycelin Tan Zhu / Loh, Hui Lin / Ng, Wen Ying / Yee, Chin Wen / Southam, Benjamin / Vicenzi, Silvia / Randall, Cameron / Yang, Cheng / Tan, Ee / Pasupuleti, Manideepika / Grewal, Avneet Kaur / Ahmad, Tauseef / Shastri, Madhur / Vicario, Carmelo /

Ronci, Maurizio / Zuccarini, Mariachiara / Bleasel, Martin / Scowen, Paul / Raffaeli, William / D'Andrea, Gianvicenzo / Chellappan, Dinesh Kumar / Jacobson, Glenn / Bissember, Alex C / Smith, Jason A / Eri, Raj / Canales, Juan / Iglesias, Miguel / Guven, Nuri / Caruso, Vanni

Frontiers in endocrinology

2021 Volume 12, Page(s) 615446

Abstract: Asperuloside is an iridoid glycoside found in many medicinal plants that has produced promising anti-obesity results in animal models. In previous studies, three months of asperuloside administration reduced food intake, body weight, and adipose masses ... ...

Abstract	Asperuloside is an iridoid glycoside found in many medicinal plants that has produced promising anti-obesity results in animal models. In previous studies, three months of asperuloside administration reduced food intake, body weight, and adipose masses in rats consuming a high fat diet (HFD). However, the mechanisms by which asperuloside exerts its anti-obesity properties were not clarified. Here, we investigated homeostatic and nutrient-sensing mechanisms regulating food intake in mice consuming HFD. We confirmed the anti-obesity properties of asperuloside and, importantly, we identified some mechanisms that could be responsible for its therapeutic effect. Asperuloside reduced body weight and food intake in mice consuming HFD by 10.5 and 12.8% respectively, with no effect on mice eating a standard chow diet. Fasting glucose and plasma insulin were also significantly reduced. Mechanistically, asperuloside significantly reduced hypothalamic mRNA ghrelin, leptin, and pro-opiomelanocortin in mice consuming HFD. The expression of fat lingual receptors (CD36, FFAR1-4), CB1R and sweet lingual receptors (TAS1R2-3) was increased almost 2-fold by the administration of asperuloside. Our findings suggest that asperuloside might exert its therapeutic effects by altering nutrient-sensing receptors in the oral cavity as well as hypothalamic receptors involved in food intake when mice are exposed to obesogenic diets. This signaling pathway is known to influence the subtle hypothalamic equilibrium between energy homeostasis and reward-induced overeating responses. The present pre-clinical study demonstrated that targeting the gustatory system through asperuloside administration could represent a promising and effective new anti-obesity strategy.
MeSH term(s)	Animals ; Anti-Obesity Agents/pharmacology ; Blood Glucose ; Body Weight/drug effects ; Cyclopentane Monoterpenes/pharmacology ; Diet, High-Fat ; Energy Intake/drug effects ; Ghrelin/metabolism ; Glucosides/pharmacology ; Hypothalamus/drug effects ; Hypothalamus/metabolism ; Insulin/blood ; Leptin/metabolism ; Male ; Mice ; Pro-Opiomelanocortin/metabolism ; Pyrans/pharmacology ; Taste Perception/drug effects ; Weight Gain/drug effects
Chemical Substances	Anti-Obesity Agents ; Blood Glucose ; Cyclopentane Monoterpenes ; Ghrelin ; Glucosides ; Insulin ; Leptin ; Pyrans ; Pro-Opiomelanocortin (66796-54-1) ; asperuloside (V3CFI02X39)
Language	English
Publishing date	2021-04-13
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2021.615446
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Ipratropium treatment of acute airways disease.

Peterson, Gregory M / Boyles, Peter J / Bleasel, Martin D / Vial, Janet H

The Annals of pharmacotherapy

2003 Volume 37, Issue 3, Page(s) 339–344

Abstract: Objective: To examine the use of ipratropium bromide in adults with acute exacerbation of either asthma or chronic obstructive pulmonary disease (COPD) during admission and at discharge from 3 teaching hospitals.: Methods: An extensive range of ... ...

Abstract	Objective: To examine the use of ipratropium bromide in adults with acute exacerbation of either asthma or chronic obstructive pulmonary disease (COPD) during admission and at discharge from 3 teaching hospitals. Methods: An extensive range of clinical and demographic data was retrospectively extracted from the medical records of consecutive patients aged >/=12 years admitted to the medical wards of the hospitals during 1999-2001 with acute exacerbations of asthma or COPD, either as a primary diagnosis or as a major comorbidity. Results: Data were gathered for 302 patients (97 with asthma, 205 with COPD). Almost 90% of all patients received ipratropium bromide during their hospital admission. The indication for using ipratropium bromide during hospitalization was considered appropriate in 84% of the asthma patients and 68% of the COPD patients. Over 20% of the patients with asthma had been using ipratropium bromide prior to the hospital admission, and almost one-third of the patients with asthma were discharged with ipratropium bromide, even though its role in chronic asthma is limited. More than 90% of the patients received nebulized drug therapy during their hospital stay, with 41% being prescribed nebulized therapy at discharge. This was often considered inappropriate, given that >50% of all patients had been using inhaler devices and nebulizers concurrently while hospitalized. Conclusions: In the majority of cases, ipratropium bromide had been used during hospitalization in accordance with guidelines for the management of acute exacerbations of asthma or COPD. However, there was also evidence of potentially inappropriate prolonged use of the agent in the community setting, particularly for asthma. Also of concern was the relatively high use of nebulized drug therapy when delivery via other means was appropriate.
MeSH term(s)	Administration, Inhalation ; Adolescent ; Adrenergic beta-2 Receptor Agonists ; Adult ; Aged ; Asthma/diagnosis ; Asthma/drug therapy ; Bronchodilator Agents/administration & dosage ; Bronchodilator Agents/therapeutic use ; Drug Utilization Review ; Female ; Hospitalization ; Humans ; Ipratropium/administration & dosage ; Ipratropium/therapeutic use ; Male ; Medication Errors ; Middle Aged ; Nebulizers and Vaporizers ; Patient Discharge ; Practice Patterns, Physicians' ; Pulmonary Disease, Chronic Obstructive/diagnosis ; Pulmonary Disease, Chronic Obstructive/drug therapy ; Retrospective Studies
Chemical Substances	Adrenergic beta-2 Receptor Agonists ; Bronchodilator Agents ; Ipratropium (GR88G0I6UL)
Language	English
Publishing date	2003-03
Publishing country	United States
Document type	Journal Article ; Multicenter Study
ZDB-ID	1101370-9
ISSN	1542-6270 ; 1060-0280
ISSN (online)	1542-6270
ISSN	1060-0280
DOI	10.1345/aph.1C263
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Multifaceted educational program increases prescribing of preventive medication for corticosteroid induced osteoporosis.

Naunton, Mark / Peterson, Gregory M / Jones, Graeme / Griffin, Gillian M / Bleasel, Martin D

The Journal of rheumatology

2004 Volume 31, Issue 3, Page(s) 550–556

Abstract: ... of patients), calcium (5% to 19%), and vitamin D (3% to 11%) all increased significantly. Prescription data ...

Abstract	Objective: Despite evidence that oral corticosteroids increase fracture risk and the existence of guidelines for the prevention of corticosteroid induced osteoporosis, few patients prescribed longterm corticosteroids receive osteoporosis prevention. We performed a controlled trial of a comprehensive educational program aimed at increasing the use of osteoporosis preventive therapy in patients prescribed longterm oral corticosteroids. Methods: The intervention was conducted in Southern Tasmania, Australia, using Northern Tasmania as a control area. All general practitioners and community pharmacies were sent educational material and locally produced guidelines on the prevention of corticosteroid induced osteoporosis. This was followed by academic detailing visits and reminders. Pharmacists were provided with supplies of an educational refrigerator magnet, intended for patients. Outcomes were measured using evaluation feedback from the general practitioners and pharmacists, and drug utilization data provided by (1). a series of patients presenting to hospital and taking oral corticosteroids for at least 3 consecutive months; and (2). dispensing of osteoporosis preventive therapy under the Australian Pharmaceutical Benefits Scheme. Results: The prevalence of osteoporosis preventive therapy increased from 31% of admitted hospital patients taking longterm oral corticosteroids to 57% postintervention (p < 0.0001). The use of bisphosphonates (6% to 24% of patients), calcium (5% to 19%), and vitamin D (3% to 11%) all increased significantly. Prescription data also indicated a significant (p < 0.01) increase in the use of osteoporosis preventive therapy in the intervention region. Conclusion: A multifaceted education program, incorporating academic detailing of general practitioners and community pharmacists, increased the use of osteoporosis prevention strategies in longterm oral corticosteroid users.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Calcium/administration & dosage ; Chemoprevention/methods ; Diphosphonates/administration & dosage ; Education, Continuing/methods ; Female ; Glucocorticoids/adverse effects ; Health Education/methods ; Humans ; Information Dissemination/methods ; Male ; Middle Aged ; Osteoporosis/chemically induced ; Osteoporosis/prevention & control ; Practice Guidelines as Topic ; Practice Patterns, Physicians' ; Prednisolone/adverse effects ; Tasmania ; Vitamin D/administration & dosage
Chemical Substances	Diphosphonates ; Glucocorticoids ; Vitamin D (1406-16-2) ; Prednisolone (9PHQ9Y1OLM) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2004-03
Publishing country	Canada
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	194928-7
ISSN	1499-2752 ; 0315-162X
ISSN (online)	1499-2752
ISSN	0315-162X
Database	MEDical Literature Analysis and Retrieval System OnLINE

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