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As of October 30, there have been 392 confirmed cases of new crowns nationwide
.
Since this round of the epidemic was triggered by elderly tour groups, most of the elderly patients were involved (40% over 60 years old), and the proportion of severe cases was also higher than previous epidemics
.
As the number of diagnosed elderly patients increases, how to diagnose and treat new coronary pneumonia for high-risk groups and prevent the course of the disease from progressing to serious illness is particularly important
.
Recently, "The Lancet Global Health" (IF: 26.
763) showed that the antidepressant fluvoxamine can reduce the possibility of severe COVID-19 patients.
No relevant large-scale clinical randomized controlled studies have been published before
.
In other words, this antidepressant, which was used clinically as early as the last century, is likely to become a cheap substitute for the new crown-specific immunoglobulin
.
This is undoubtedly good news for areas where vaccines have not yet been popularized and economically underdeveloped
.
How was the sudden emergence of fluvoxamine found? In 1983, fluvoxamine was developed by Kali-Duphar and launched in Switzerland under the name Floxyfral
.
11 years later, it was approved for listing by the FDA in the United States
.
As an SSRI antidepressant, it can be said to be a veteran level, used in severely depressed patients in various countries, and it is also the first SSRI drug for obsessive-compulsive disorder
.
In 2005, the drug's feats were added to the feat-Japan's first drug approved for social anxiety disorder
.
So far, this antidepressant with the trade name "Lan Shi" is known to everyone in the field of psychiatry
.
Source: Fluvoxamine maleate is the only selective serotonin (5-HT) reuptake inhibitor (SSRI) with a single ring structure, and its affinity for serotonin transporter is norepinephrine transporter 100 times
.
By selectively inhibiting the reuptake of 5-HT by the presynaptic membrane of the central nerve, increasing the effective concentration of 5-HT in the synaptic cleft to exert an antidepressant effect
.
In the early stage of the epidemic, everyone knew very little about the new crown virus.
This is a dead horse as a living horse doctor.
Did you just use your antidepressants for the patients? Obviously it is impossible
.
There is no specific medicine for the new crown, and only symptomatic treatment can be done.
According to the NIH's COVID-19 treatment guidelines, the diagnosis and treatment of the new crown virus can be roughly divided into antiviral therapy, anti-coronavirus antibodies, cell therapy, immunomodulatory therapy, and antithrombotic therapy , And supportive treatment
.
Among them, immunomodulators are used to deal with the excessive inflammatory response of the new coronavirus infection.
The first immunomodulatory agent used in critically ill patients is the universal dexamethasone
.
However, using "dimi" to deal with mild or early diagnosed patients is a little bit "killing chickens with a sledgehammer", and the side effects are not small
.
The development of new drugs is not an overnight task.
Doctors turn their attention to other old drugs that can also regulate the immune response and reduce inflammation, such as the familiar colchicine, budesonide, and this antidepressant fluvoxamine
.
Of course, we can reasonably suspect that the daily high-pressure medical care group is already familiar with the pharmacological mechanism of antidepressants.
This sad fact superimposed on an appropriate coincidence has created the sudden emergence of fluvoxamine
.
Source: How did unsplash get the confirmation step by step? As early as the beginning of the spread of the new crown epidemic, The Lancet discovered pneumonia caused by the new coronavirus infection, which is prone to lung damage due to excessive inflammation, which in turn worsens the condition and even death
.
In order to prevent the new coronavirus from attacking the lungs, regulating the immune response is a key step
.
One potential mechanism of immune regulation is σ-1 receptor (S1R) activation
.
Fluvoxamine's high affinity for S1R was confirmed as early as in Japan's basic research (2014).
This prescient research has also become the theoretical basis for fluvoxamine to invest in animal experimental research on the new coronavirus
.
On November 12, 2020, JAMA published an exciting fluvoxamine clinical trial study
.
In this double-blind, placebo-controlled randomized clinical trial, 152 new coronavirus-positive outpatients received fluvoxamine within 15 days, and none of the patients became severely ill; while in the placebo group, 6 (8.
3%) ) The patient's condition deteriorated
.
The researchers finally mentioned that this is a small, single-area study, with insufficient follow-up, and an unclear mechanism.
It needs to be repeated in large trials with more heterogeneous populations
.
These regrets were further remedied in the TOGETHER trial published recently
.
In the TOGETHER trial, the research team collected patient data from 11 cities in Brazil and screened 9803 potential participants for inclusion in the trial
.
On August 5, 2021, 1497 high-risk patients were assigned to fluvoxamine group (100 mg bid, for 10 consecutive days) or placebo group, and 1826 were randomly assigned to other treatment groups
.
In addition, the researchers also collected detailed data such as 28-day follow-up
.
This is the first large-scale clinical trial of fluvoxamine in patients with new crowns
.
The results showed that 79 patients (11%) in the fluvoxamine group experienced deterioration, while 119 (16%) patients in the placebo group had worsening conditions.
Most patients with worsening conditions required hospitalization (87%)
.
Figure.
The efficacy probability and Bayesian relative risk of hospitalization in the TOGETHER trial are based on the Bayesian beta-binomial model.
There is evidence that fluvoxamine can effectively reduce the "hospitalization" endpoint
.
"Hospitalization" is defined as staying in the hospital or being transferred to a tertiary hospital under the condition of disease progression (Figure A: ITT population; Figure B: Modified ITT population)
.
Compared with the placebo group, the fluvoxamine group had a lower end-point event rate (99.
8% for the ITT population and 99.
7% for the modified TT population)
.
In the analysis of the secondary outcome, there was no significant difference in the data between the fluvoxamine group and the placebo group: · Virus clearance rate on day 7 (p=0.
09) · Hospitalization due to new coronavirus (p=0.
10) · All-cause hospitalization (p=0.
09), length of hospitalization (p=0.
11), days of hospitalization (p=0.
06), mortality (p=0.
24), time of death (p=0.
49), days of mechanical ventilation (p= 0.
90)· Recovery time (p=0.
79)· PROMIS Global Physical Scale (p=0.
55)· Psychological Scale (p=0·32) Fig.
Subgroup analysis of fluvoxamine and placebo in TOGETHER trial Tolerability issues, 84 patients stopped fluvoxamine treatment, 64 patients stopped placebo treatment, there was no significant difference in the number of adverse events in the two groups of patients during treatment, but the absolute number of fluvoxamine group Lower than the placebo group, it may be that fluvoxamine's anti-inflammatory effect reduced the patient's lower respiratory tract infection rate
.
This adverse reaction data is consistent with the results of the previous study that "confirmed patients receiving fluvoxamine treatment require less hospitalization and/or mechanical ventilation"
.
All the above data and evidence clarify the wide availability of fluvoxamine
.
Some researchers boldly predict that this study may directly shake up the revision of the COVID-19 diagnosis and treatment guidelines
.
However, the underlying mechanism of fluvoxamine against new coronary pneumonia is still divided.
The preliminary research results suggest that the main reason is fluvoxamine's anti-inflammatory effect by activating S1R
.
Another mechanism may be the antiplatelet activity of fluvoxamine, which reduces the risk of thrombosis
.
Some researchers believe that this may be related to fluvoxamine's ability to increase the level of serum melatonin
.
But even so, the universality of fluvoxamine is still worth looking forward to
.
Where is fluvoxamine universal? Fluvoxamine, as a cheap existing drug, can reduce the high-risk population's need for advanced care of diseases, save medical resources, and reduce social pressure
.
According to the price of fluvoxamine on a drug sales platform, according to the course of treatment on the TOGETHER trial (100mg bid, 10 consecutive days), a total of 40 tablets need to be taken
.
The cost of buying two boxes without medical insurance reimbursement is 130 yuan .
Most importantly, we are very familiar with it
.
So far, fluvoxamine has been clinically used for 27 years and has been taken by hundreds of millions of patients at least.
Its clinical reactions and side effects are much more familiar than newly developed vaccines and drugs
.
The unique safety and security of this "old medicine" can help doctors get better promotion, perhaps even easier than popularizing vaccination
.
However, as of October 19, 2021, the NIH's COVID-19 diagnosis and treatment guidelines for fluvoxamine are still "not yet fully evidenced to be recommended for the treatment of COVID-19
.
"
After all, these clinical studies also have certain limitations.
For example, the nursing operations during the trial have not been standardized and unified, and the sampling area is only within Brazil
.
To promote the clinical application of this affordable drug, more data from large-scale clinical randomized controlled trials is needed
.
The road is still long
.
Figure.
From Reference 1 Reis G, Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial [J]The Lancet Global Health .
2021,10 DOI: https://doi.
org/10.
1016/S2214-109X(21)00448-42 Lenze EJ, Mattar C, Zorumski CF, et al.
Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19 : A Randomized Clinical Trial [J].
JAMA, 2020.
3 Rosen DA, Seki SM, Fernández-Castañeda A, et al.
Modulation of the sigma-1 receptor–IRE1 pathway is beneficial in preclinical models of inflammation and sepsis[J].
Science Translational Medicine, 2019, 11(478).
4 Homolak J, Kodvanj I.
Widely available lysosome targeting agents should be considered as a potential therapy for COVID-19[J].
International Journal of Antimicrobial Agents, 2020: 106044.
5 Mehta P, McAuley DF, Brown M, et al.
COVID-19: consider cytokine storm syndromes and immunosuppression.
Lancet.
2020;395(10229):1033-1034.
6.
Prasad A, Prasad M .
Single virus targeting multiple organs.
Front Med (Lausanne).
2020;7:370.
7 Ishima T, Fujita Y, Hashimoto K.
Interaction of new antidepressants with sigma-1 receptor chaperones and their potentiation of neurite outgrowth in PC12 cells.
Eur J Pharmacol .
2014;727:167-173.
Written by R.
Editor | Jennie Click below "read the full text" to download the Metz Medical APPFujita Y, Hashimoto K.
Interaction of new antidepressants with sigma-1 receptor chaperones and their potentiation of neurite outgrowth in PC12 cells.
Eur J Pharmacol.
2014;727:167-173.
Written by | R.
Editor | Jennie click below to read the full text ”Download Metz Medical APPFujita Y, Hashimoto K.
Interaction of new antidepressants with sigma-1 receptor chaperones and their potentiation of neurite outgrowth in PC12 cells.
Eur J Pharmacol.
2014;727:167-173.
Written by R.
Editor | Jennie Click below to read the full text ”Download Metz Medical APP
.
Since this round of the epidemic was triggered by elderly tour groups, most of the elderly patients were involved (40% over 60 years old), and the proportion of severe cases was also higher than previous epidemics
.
As the number of diagnosed elderly patients increases, how to diagnose and treat new coronary pneumonia for high-risk groups and prevent the course of the disease from progressing to serious illness is particularly important
.
Recently, "The Lancet Global Health" (IF: 26.
763) showed that the antidepressant fluvoxamine can reduce the possibility of severe COVID-19 patients.
No relevant large-scale clinical randomized controlled studies have been published before
.
In other words, this antidepressant, which was used clinically as early as the last century, is likely to become a cheap substitute for the new crown-specific immunoglobulin
.
This is undoubtedly good news for areas where vaccines have not yet been popularized and economically underdeveloped
.
How was the sudden emergence of fluvoxamine found? In 1983, fluvoxamine was developed by Kali-Duphar and launched in Switzerland under the name Floxyfral
.
11 years later, it was approved for listing by the FDA in the United States
.
As an SSRI antidepressant, it can be said to be a veteran level, used in severely depressed patients in various countries, and it is also the first SSRI drug for obsessive-compulsive disorder
.
In 2005, the drug's feats were added to the feat-Japan's first drug approved for social anxiety disorder
.
So far, this antidepressant with the trade name "Lan Shi" is known to everyone in the field of psychiatry
.
Source: Fluvoxamine maleate is the only selective serotonin (5-HT) reuptake inhibitor (SSRI) with a single ring structure, and its affinity for serotonin transporter is norepinephrine transporter 100 times
.
By selectively inhibiting the reuptake of 5-HT by the presynaptic membrane of the central nerve, increasing the effective concentration of 5-HT in the synaptic cleft to exert an antidepressant effect
.
In the early stage of the epidemic, everyone knew very little about the new crown virus.
This is a dead horse as a living horse doctor.
Did you just use your antidepressants for the patients? Obviously it is impossible
.
There is no specific medicine for the new crown, and only symptomatic treatment can be done.
According to the NIH's COVID-19 treatment guidelines, the diagnosis and treatment of the new crown virus can be roughly divided into antiviral therapy, anti-coronavirus antibodies, cell therapy, immunomodulatory therapy, and antithrombotic therapy , And supportive treatment
.
Among them, immunomodulators are used to deal with the excessive inflammatory response of the new coronavirus infection.
The first immunomodulatory agent used in critically ill patients is the universal dexamethasone
.
However, using "dimi" to deal with mild or early diagnosed patients is a little bit "killing chickens with a sledgehammer", and the side effects are not small
.
The development of new drugs is not an overnight task.
Doctors turn their attention to other old drugs that can also regulate the immune response and reduce inflammation, such as the familiar colchicine, budesonide, and this antidepressant fluvoxamine
.
Of course, we can reasonably suspect that the daily high-pressure medical care group is already familiar with the pharmacological mechanism of antidepressants.
This sad fact superimposed on an appropriate coincidence has created the sudden emergence of fluvoxamine
.
Source: How did unsplash get the confirmation step by step? As early as the beginning of the spread of the new crown epidemic, The Lancet discovered pneumonia caused by the new coronavirus infection, which is prone to lung damage due to excessive inflammation, which in turn worsens the condition and even death
.
In order to prevent the new coronavirus from attacking the lungs, regulating the immune response is a key step
.
One potential mechanism of immune regulation is σ-1 receptor (S1R) activation
.
Fluvoxamine's high affinity for S1R was confirmed as early as in Japan's basic research (2014).
This prescient research has also become the theoretical basis for fluvoxamine to invest in animal experimental research on the new coronavirus
.
On November 12, 2020, JAMA published an exciting fluvoxamine clinical trial study
.
In this double-blind, placebo-controlled randomized clinical trial, 152 new coronavirus-positive outpatients received fluvoxamine within 15 days, and none of the patients became severely ill; while in the placebo group, 6 (8.
3%) ) The patient's condition deteriorated
.
The researchers finally mentioned that this is a small, single-area study, with insufficient follow-up, and an unclear mechanism.
It needs to be repeated in large trials with more heterogeneous populations
.
These regrets were further remedied in the TOGETHER trial published recently
.
In the TOGETHER trial, the research team collected patient data from 11 cities in Brazil and screened 9803 potential participants for inclusion in the trial
.
On August 5, 2021, 1497 high-risk patients were assigned to fluvoxamine group (100 mg bid, for 10 consecutive days) or placebo group, and 1826 were randomly assigned to other treatment groups
.
In addition, the researchers also collected detailed data such as 28-day follow-up
.
This is the first large-scale clinical trial of fluvoxamine in patients with new crowns
.
The results showed that 79 patients (11%) in the fluvoxamine group experienced deterioration, while 119 (16%) patients in the placebo group had worsening conditions.
Most patients with worsening conditions required hospitalization (87%)
.
Figure.
The efficacy probability and Bayesian relative risk of hospitalization in the TOGETHER trial are based on the Bayesian beta-binomial model.
There is evidence that fluvoxamine can effectively reduce the "hospitalization" endpoint
.
"Hospitalization" is defined as staying in the hospital or being transferred to a tertiary hospital under the condition of disease progression (Figure A: ITT population; Figure B: Modified ITT population)
.
Compared with the placebo group, the fluvoxamine group had a lower end-point event rate (99.
8% for the ITT population and 99.
7% for the modified TT population)
.
In the analysis of the secondary outcome, there was no significant difference in the data between the fluvoxamine group and the placebo group: · Virus clearance rate on day 7 (p=0.
09) · Hospitalization due to new coronavirus (p=0.
10) · All-cause hospitalization (p=0.
09), length of hospitalization (p=0.
11), days of hospitalization (p=0.
06), mortality (p=0.
24), time of death (p=0.
49), days of mechanical ventilation (p= 0.
90)· Recovery time (p=0.
79)· PROMIS Global Physical Scale (p=0.
55)· Psychological Scale (p=0·32) Fig.
Subgroup analysis of fluvoxamine and placebo in TOGETHER trial Tolerability issues, 84 patients stopped fluvoxamine treatment, 64 patients stopped placebo treatment, there was no significant difference in the number of adverse events in the two groups of patients during treatment, but the absolute number of fluvoxamine group Lower than the placebo group, it may be that fluvoxamine's anti-inflammatory effect reduced the patient's lower respiratory tract infection rate
.
This adverse reaction data is consistent with the results of the previous study that "confirmed patients receiving fluvoxamine treatment require less hospitalization and/or mechanical ventilation"
.
All the above data and evidence clarify the wide availability of fluvoxamine
.
Some researchers boldly predict that this study may directly shake up the revision of the COVID-19 diagnosis and treatment guidelines
.
However, the underlying mechanism of fluvoxamine against new coronary pneumonia is still divided.
The preliminary research results suggest that the main reason is fluvoxamine's anti-inflammatory effect by activating S1R
.
Another mechanism may be the antiplatelet activity of fluvoxamine, which reduces the risk of thrombosis
.
Some researchers believe that this may be related to fluvoxamine's ability to increase the level of serum melatonin
.
But even so, the universality of fluvoxamine is still worth looking forward to
.
Where is fluvoxamine universal? Fluvoxamine, as a cheap existing drug, can reduce the high-risk population's need for advanced care of diseases, save medical resources, and reduce social pressure
.
According to the price of fluvoxamine on a drug sales platform, according to the course of treatment on the TOGETHER trial (100mg bid, 10 consecutive days), a total of 40 tablets need to be taken
.
The cost of buying two boxes without medical insurance reimbursement is 130 yuan .
Most importantly, we are very familiar with it
.
So far, fluvoxamine has been clinically used for 27 years and has been taken by hundreds of millions of patients at least.
Its clinical reactions and side effects are much more familiar than newly developed vaccines and drugs
.
The unique safety and security of this "old medicine" can help doctors get better promotion, perhaps even easier than popularizing vaccination
.
However, as of October 19, 2021, the NIH's COVID-19 diagnosis and treatment guidelines for fluvoxamine are still "not yet fully evidenced to be recommended for the treatment of COVID-19
.
"
After all, these clinical studies also have certain limitations.
For example, the nursing operations during the trial have not been standardized and unified, and the sampling area is only within Brazil
.
To promote the clinical application of this affordable drug, more data from large-scale clinical randomized controlled trials is needed
.
The road is still long
.
Figure.
From Reference 1 Reis G, Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial [J]The Lancet Global Health .
2021,10 DOI: https://doi.
org/10.
1016/S2214-109X(21)00448-42 Lenze EJ, Mattar C, Zorumski CF, et al.
Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19 : A Randomized Clinical Trial [J].
JAMA, 2020.
3 Rosen DA, Seki SM, Fernández-Castañeda A, et al.
Modulation of the sigma-1 receptor–IRE1 pathway is beneficial in preclinical models of inflammation and sepsis[J].
Science Translational Medicine, 2019, 11(478).
4 Homolak J, Kodvanj I.
Widely available lysosome targeting agents should be considered as a potential therapy for COVID-19[J].
International Journal of Antimicrobial Agents, 2020: 106044.
5 Mehta P, McAuley DF, Brown M, et al.
COVID-19: consider cytokine storm syndromes and immunosuppression.
Lancet.
2020;395(10229):1033-1034.
6.
Prasad A, Prasad M .
Single virus targeting multiple organs.
Front Med (Lausanne).
2020;7:370.
7 Ishima T, Fujita Y, Hashimoto K.
Interaction of new antidepressants with sigma-1 receptor chaperones and their potentiation of neurite outgrowth in PC12 cells.
Eur J Pharmacol .
2014;727:167-173.
Written by R.
Editor | Jennie Click below "read the full text" to download the Metz Medical APPFujita Y, Hashimoto K.
Interaction of new antidepressants with sigma-1 receptor chaperones and their potentiation of neurite outgrowth in PC12 cells.
Eur J Pharmacol.
2014;727:167-173.
Written by | R.
Editor | Jennie click below to read the full text ”Download Metz Medical APPFujita Y, Hashimoto K.
Interaction of new antidepressants with sigma-1 receptor chaperones and their potentiation of neurite outgrowth in PC12 cells.
Eur J Pharmacol.
2014;727:167-173.
Written by R.
Editor | Jennie Click below to read the full text ”Download Metz Medical APP
