Progesterone Reverses The Side Effects Of Anti-serotonin Drugs Like Ondansetron

haidut

Member
Joined
Mar 18, 2013
Messages
18,022
Location
USA / Europe
Ray has written about the benefits of 5-HT3 antagonists like ondansetron. Tehse drugs have remerkable properties are known to have central as well as peripheral effects. Ondansteron is one of the most potent drugs available for reversing learned helplessness and it does so in doses below 4mg, which is the starting therapeutic dose. Unfortunately, drugs like ondansetron have a number of potentially serious side effects, the most prominent of which is the prolongation of the QT-interval. That side effect can lead to dangerous arrhythmia and even cardiac arrest.

This showed that the combined administration of 400mg oral progesterone for 7 days and a drug (ibutilide) that prolongs the QT-interval essentially reversed that side effect of the drug. The plasma concentrations achievable with 400mg oral progesterone can be achieved with about 600mg pregnenolone, so that approach should work as well for people using ondansetron.
The positive heart effects of progesterone are not surprising given that it is BOTH a positive ionotropic and chronotropic agent as Ray wrote in one of his articles. Estrogen is the exact opposite in this respect, so it is not far fetched to supposed that it would have opposite effects on the heart and thus also prolong the QT-interval. Yet another reason to keep estrogen under control.

http://medicalxpress.com/news/2016-04-progesterone-attenuates-drug-induced-qt-interval.html
"...James E. Tisdale, Pharm.D., from Purdue University in Indianapolis, and colleagues conducted a double-blind crossover study involving 19 healthy females. Participants were randomized to receive progesterone 400 mg or matching placebo once daily for seven days timed to the menses phase of the menstrual cycle, with a 49-day between-phase washout period. Ibutilide was infused over 10 minutes on day seven, after which, QT intervals were recorded; blood samples were collected for 12 hours. To calculate individualized heart rate-corrected QT intervals (QTcI), subjects underwent electrocardiographic monitoring for 12 hours prior to the treatment phases."

"...Oral progesterone administration attenuates drug-induced QTcI lengthening," the authors write."
 

haidut

Member
Thread starter
Joined
Mar 18, 2013
Messages
18,022
Location
USA / Europe
Is QT an issue with tianeptine?

Not that I know of. It seems to be specific to the *setron drugs acting on 5-HT3.
Broken heart: depression in cardiovascular disease
"...Also, cardiac events were more frequent among patients on nortriptyline (18%) compared with paroxetine (2%). Moreover, other antidepressants, such as tianeptine, are also known to be free of deleterious cardiovascular effects and interactions in polymedicated patients due to lack of action on cytochrome P-450; tianeptine can thus be freely administered in depressed patients with concomitant cardiovascular disease."


There is a study specifically absolving cyproheptadine of the *setron sins though.
The conventional antihistamine drug cyproheptadine lacks QT-interval-prolonging action in halothane-anesthetized guinea pigs: comparison with hydro... - PubMed - NCBI
 

Regina

Member
Joined
Aug 17, 2016
Messages
3,748
Location
Chicago
Ray has written about the benefits of 5-HT3 antagonists like ondansetron. Tehse drugs have remerkable properties are known to have central as well as peripheral effects. Ondansteron is one of the most potent drugs available for reversing learned helplessness and it does so in doses below 4mg, which is the starting therapeutic dose. Unfortunately, drugs like ondansetron have a number of potentially serious side effects, the most prominent of which is the prolongation of the QT-interval. That side effect can lead to dangerous arrhythmia and even cardiac arrest.

This showed that the combined administration of 400mg oral progesterone for 7 days and a drug (ibutilide) that prolongs the QT-interval essentially reversed that side effect of the drug. The plasma concentrations achievable with 400mg oral progesterone can be achieved with about 600mg pregnenolone, so that approach should work as well for people using ondansetron.
The positive heart effects of progesterone are not surprising given that it is BOTH a positive ionotropic and chronotropic agent as Ray wrote in one of his articles. Estrogen is the exact opposite in this respect, so it is not far fetched to supposed that it would have opposite effects on the heart and thus also prolong the QT-interval. Yet another reason to keep estrogen under control.

http://medicalxpress.com/news/2016-04-progesterone-attenuates-drug-induced-qt-interval.html
"...James E. Tisdale, Pharm.D., from Purdue University in Indianapolis, and colleagues conducted a double-blind crossover study involving 19 healthy females. Participants were randomized to receive progesterone 400 mg or matching placebo once daily for seven days timed to the menses phase of the menstrual cycle, with a 49-day between-phase washout period. Ibutilide was infused over 10 minutes on day seven, after which, QT intervals were recorded; blood samples were collected for 12 hours. To calculate individualized heart rate-corrected QT intervals (QTcI), subjects underwent electrocardiographic monitoring for 12 hours prior to the treatment phases."

"...Oral progesterone administration attenuates drug-induced QTcI lengthening," the authors write."
Hello Haidut,

Would this be a concern with Ritanserin? Thanks!
 

haidut

Member
Thread starter
Joined
Mar 18, 2013
Messages
18,022
Location
USA / Europe

DaveFoster

Member
Joined
Jul 23, 2015
Messages
4,926
Location
Spokane, Washington
Apparently mirtazapine is not exempt from cardiovascular side effects:

Antidepressants and the risk of sudden cardiac death and ventricular arrhythmia. - PubMed - NCBI

PURPOSE:
To examine the association between exposure to antidepressants and emergency department or inpatient admission for sudden cardiac death and ventricular arrhythmia (SD/VA), and to examine the impact of dose and cytochrome P-450 inhibition.

METHODS:
A cohort study was conducted using 1999-2003 Medicaid claims data from beneficiaries of five large states, supplemented with Medicare claims for dually eligible individuals. Exposures were prescription claims for antidepressants of interest or a reference antidepressant. Outcomes were incident first-listed emergency department or principal inpatient diagnoses indicative of SD/VA originating in the outpatient setting, an outcome previously found to have a positive predictive value of 85%.

RESULTS:
In 1.3 million person-years of antidepressant exposure, we identified 4222 SD/VA outcomes for a rate of 3.3/1000 person-years (95%CI, 3.2-3.4). Compared with paroxetine (a referent with a putatively favorable cardiovascular risk profile), adjusted hazard ratios (HRs) were 0.80 (0.67-0.95) for bupropion, 1.24 (0.93-1.65) for doxepin, 0.79 (0.55-1.15) for lithium, and 1.26 (1.11-1.42) for mirtazapine. HRs for amitriptyline, citalopram, fluoxetine, nefazodone, nortriptyline, sertraline, trazodone, and venlafaxine were near unity. For antidepressants having nonnull risks (bupropion and mirtazapine), we observed no relationship with antidepressant dose and some relationships with concomitant cytochrome P-450 inhibition.

CONCLUSIONS:
Of antidepressants studied, only mirtazapine had a statistically significantly greater SD/VA risk versus paroxetine. However, baseline differences between these users suggest that this finding may be attributable to residual confounding. Eleven other antidepressants had SD/VA risks no greater than that of paroxetine, thereby providing reassurance regarding the comparative cardiovascular safety of antidepressants.

@haidut

Do you think co-administered cyproheptadine can help prevent these effects in the same way that it prevents fibrosis from ergot derivatives? I might recall that you mentioned it protects against ondansetron as well, but I may be incorrect.
 

ddjd

Member
Joined
Jul 13, 2014
Messages
3,775
Ray has written about the benefits of 5-HT3 antagonists like ondansetron. Tehse drugs have remerkable properties are known to have central as well as peripheral effects. Ondansteron is one of the most potent drugs available for reversing learned helplessness and it does so in doses below 4mg, which is the starting therapeutic dose. Unfortunately, drugs like ondansetron have a number of potentially serious side effects, the most prominent of which is the prolongation of the QT-interval. That side effect can lead to dangerous arrhythmia and even cardiac arrest.

This showed that the combined administration of 400mg oral progesterone for 7 days and a drug (ibutilide) that prolongs the QT-interval essentially reversed that side effect of the drug. The plasma concentrations achievable with 400mg oral progesterone can be achieved with about 600mg pregnenolone, so that approach should work as well for people using ondansetron.
The positive heart effects of progesterone are not surprising given that it is BOTH a positive ionotropic and chronotropic agent as Ray wrote in one of his articles. Estrogen is the exact opposite in this respect, so it is not far fetched to supposed that it would have opposite effects on the heart and thus also prolong the QT-interval. Yet another reason to keep estrogen under control.

haidut would this QT heart issue be of concern with regards to 5aDHP, as you mentioned it antagonises the 5ht3 receptor
 

haidut

Member
Thread starter
Joined
Mar 18, 2013
Messages
18,022
Location
USA / Europe
haidut would this QT heart issue be of concern with regards to 5aDHP, as you mentioned it antagonises the 5ht3 receptor

Not that I know of. AFAIK, the QT issue is specific to the *setron drugs and other specific 5-HT3 antagonists like tropanserin do not have this issue.
 
Similar threads
Thread starter Title Forum Replies Date
haidut Transdermal Progesterone Reverses Osteoporosis Scientific Studies 4
A Progesterone for recovering addict Supplements 9
C Should I supplement thyroid or progesterone first? Or both at the same time? Ask For Help or Advice 23
koshko Progesterone low blood pressure 80/40. Help! Ask For Help or Advice 2
J Why is finasteride more effective than progesterone? Hair & Nails 2
K Progesterone Best Practices? Thyroid and Hormones 5
belcanto Estrogen, iron, degenerative aging, and progesterone - and Lactoferrin! Articles & Newsletters Discussion 20
P Thyroid and Progesterone make me look (and feel) a bit stoned Ask For Help or Advice 0
T Progesterone preventing Prostate Cancer Cancer 1
C Help with DUTCH results- low estrogen, low progesterone but normal cortisol? Blood Work, Labs 4
jpgio How much topical progesterone (progest-e) to start with for a man? Progesterone 14
M Enzyme question progesterone allopreg 3α-Hydroxysteroid dehydrogenase Male Issues 0
L Is healthnatura’s progesterone inferior to Ray Peat’s ProgestE? Progesterone 6
J Progesterone dosage for boosting cortisol/T3 utilization Progesterone 8
J Is progesterone safe? Supplements, Pharmaceutical Drugs 2
Elie Does the estrogen and progesterone the monthly cycle make sense? Thyroid and Hormones 3
Soren Pregnenolone vs Progesterone for Back Pain, Endotoxin, Parkinsons Disease Ask For Help or Advice 6
G Extracting smaller doses from 100mg Progesterone capsules Pharmaceutical Drugs 0
P Progesterone feminizing effects? Progesterone 30
S Pregnenolone vs Progesterone for under developed cognitive function Ask For Help or Advice 65
ddjd Taking Progesterone whilst breast feeding newborn?? Ask For Help or Advice 5
L Ray Peat Interview June 2021 - DR, RP, GD - #61: Bodybuilding and Steroids | Progesterone for Men? | Basic Bioenergetic Therapies with Ray Peat Interviews 2
Mauritio Long term DHEA supplementation doubles androgens and progesterone in males Scientific Studies 26
Mito Progesterone and Allopregnanolone Neuroprotective Effects Progesterone 1
P Progesterone Suppresses GAD enzyme MRNA (If progesterone excites you, it may be glutamate) Progesterone 2
haidut Stress causes/exacerbates allergies, pregnenolone/progesterone therapeutic Scientific Studies 2
N Progesterone soaking my panties help! Supplements, Pharmaceutical Drugs 97
L Postpartum Progesterone issues Ask For Help or Advice 1
P Topical Progesterone to heal scar tissue? Progesterone 22
F How to lower Progesterone? and how long till supplemented Pregnenolone leaves my system? Ask For Help or Advice 7
P NOW Progesterone Cream - Any good? Progesterone 16
H How long will it take for progesterone to reverse hirsutism Progesterone 4
S Anyone got a trusted topical progesterone cream they use?? Progesterone 7
U Progesterone use in pregnancy causes homosexuality? Female Issues 3
P Best OTC Progesterone to buy? Progesterone 6
jzone56 Progesterone first observations Progesterone 4
A Progesterone increases libido? Progesterone 13
L Progesterone dosage for dog Animals 11
maillol Progesterone, Progesterone Receptors and Prolactin Scientific Studies 3
P Pregnenolone/Progesterone help? Ask For Help or Advice 1
Mito Progesterone suppresses the progression of colonic carcinoma Cancer 4
haidut Stress (cortisol) causes pre-term birth by blocking progesterone Scientific Studies 4
haidut DHT / Progesterone / aspirin treat, cortisol ineffective, PUFA promotes prostate cancer Scientific Studies 2
B 3 Meathead Chemists talk Progesterone Progesterone 31
Drareg Progesterone could reduce the severity of their COVID-19 Articles & Scientific Studies 15
B Progesterone injections for covid 19 Progesterone 0
bogbody Biolabs Pro Progesterone Cream Supplements, Pharmaceutical Drugs 19
P Progesterone receptors and serotonin levels in colon epithelial cells from females with slow transit constipation (P4 lowers SERT) Progesterone 3
A Finasteride vs Progesterone Hair & Nails 16
Sam321 Progesterone: starting dose for resolving insomnia Ask For Help or Advice 18

Similar threads

Top