If Serotonin Excess Causes Fibrosis, Why Do Drugs Inhibiting Serotonin Cause Fibrosis

[ecstatichamster]

If serotonin excess causes fibrosis, why do drugs inhibiting serotonin cause fibrosis...drugs such as cabergoline or bromocriptine can cause fibrosis, but if they inhibit serotonin which causes fibrosis, how does that work?

 

[Pointless]

A pro-dopamine drug that does not raise serotonin is the exception. Most dopaminergics are serotonergic, also.

http://www.ncbi.nlm.nih.gov/pubmed/925686

 

[haidut]

If serotonin excess causes fibrosis, why do drugs inhibiting serotonin cause fibrosis...drugs such as cabergoline or bromocriptine can cause fibrosis, but if they inhibit serotonin which causes fibrosis, how does that work?

All LSD-derivatives with the exception of lisuride activate the 5-HT2B "receptor" as well as 5-HT1, 5-HT3, and even 5-HT6. Drugs like bromocriptine, cabergoline, methysergide, etc are really best thought of as mixed dopamine-serotonin agonists with predominantly dopaminergic tone in lower doses and higher risk of fibrosis from higher doses. It's the 5-HT2B receptor activation that is responsible for both fibrosis and hallucinogenic effects of LSD and its derivatives. Terguride and lisuride are strong antagonists on 5-HT2B and this is why they are being patented for heart failure and cirrhosis. Cyproheptadine is also a strong antagonist on 5-HT2B, as is ritanserin which I am about to release as a research chemical product.

 

[Koveras]

All LSD-derivatives with the exception of lisuride activate the 5-HT2B "receptor" as well as 5-HT1, 5-HT3, and even 5-HT6. Drugs like bromocriptine, cabergoline, methysergide, etc are really best thought of as mixed dopamine-serotonin agonists with predominantly dopaminergic tone in lower doses and higher risk of fibrosis from higher doses. It's the 5-HT2B receptor activation that is responsible for both fibrosis and hallucinogenic effects of LSD and its derivatives. Terguride and lisuride are strong antagonists on 5-HT2B and this is why they are being patented for heart failure and cirrhosis. Cyproheptadine is also a strong antagonist on 5-HT2B, as is ritanserin which I am about to release as a research chemical product.

Isn't it the 5-HT2A that is responsible for the hallucinogenic effects, of which Lisuride is technically an agonist (but without the traditional effects)?

LSD but not lisuride disrupts prepulse inhibition in rats by activating the 5-HT(2A) receptor. - PubMed - NCBI

 

[haidut]

Isn't it the 5-HT2A that is responsible for the hallucinogenic effects, of which Lisuride is technically an agonist (but without the traditional effects)?

LSD but not lisuride disrupts prepulse inhibition in rats by activating the 5-HT(2A) receptor. - PubMed - NCBI

I don't think it is fully known, but it seems to be the 5-HT2 receptor. This stud on lisuride claims it is both 5-HT2A and 5-HT2C that is involved.
Re-evaluation of lisuride pharmacology: 5-hydroxytryptamine1A receptor-mediated behavioral effects overlap its other properties in rats. - PubMed - NCBI

However, bromocriptine, which is an agonist on both of these receptor subtypes is not hallucinogenic.

 

[paymanz]

because bromo is also serotonin 2b receptoragonist. cypro can counter effect that but again cypro is antagonist to dopamine too ,so i dont know if you take both the net effect is good or not.

pramipexole is interesting , there is no report of fibrosis from it-its not a agonist to serotonine 2b at all.i asked ray if he thinks its safer option to bromo , he said i dont consider prami a safe drug.he didnt clarify more unfortunetly.

 

[Koveras]

because bromo is also serotonin 2b receptoragonist. cypro can counter effect that but again cypro is antagonist to dopamine too ,so i dont know if you take both the net effect is good or not.

pramipexole is interesting , there is no report of fibrosis from it-its not a agonist to serotonine 2b at all.i asked ray if he thinks its safer option to bromo , he said i dont consider prami a safe drug.he didnt clarify more unfortunetly.

Pramipexole is primarily a Dopamine D3 receptor agonist. Most metabolic benefits have been shown thus far from D2 and D1 receptor agonism. There also seem to be more reports of 'sleep attacks'/somnolence from prami as well as issues with behavioural changes. Has not been on the market as long and less extensively studied overall.

 

[paymanz]

Pramipexole is primarily a Dopamine D3 receptor agonist. Most metabolic benefits have been shown thus far from D2 and D1 receptor agonism. There also seem to be more reports of 'sleep attacks'/somnolence from prami as well as issues with behavioural changes. Has not been on the market as long and less extensively studied overall.

good points .yes 1 and 5 ,prami doesnt nothing to them.i used prami for a while,biggest effect was on libido,very strong effect.it is good for mood too..

sleep attacks are manageable,simply taking it at night,and helps you sleep.its important to start prami at very low doses.i started at 50-100 mcg and it didnt give me some nasty symptoms others report about it.

i was gonna buy some prami today,but im not sure now.

i got some cabergoline in my hand,which can go for weeks.

 

[paymanz]

and one bad thing about dopamine agonists and hypoprolactinemia is that it decreasse tyrosine hydroxylase activity.

 

[haidut]

and one bad thing about dopamine agonists and hypoprolactinemia is that it decreasse tyrosine hydroxylase activity.

Yes, but tryptophan hydroxylase is also inhibited. Thus, dopamine and dopamine agonists lower serotonin synthesis much like pCPA does. Also, if you eat good protein that has more than 1g phenylalanine per serving tyrosine hydroxylase should come back up. Phenylalanine and some other amino acids (glycine, valine, etc but not tyrosine) upregulate its activity.

 

[paymanz]

Yes, but tryptophan hydroxylase is also inhibited. Thus, dopamine and dopamine agonists lower serotonin synthesis much like pCPA does. Also, if you eat good protein that has more than 1g phenylalanine per serving tyrosine hydroxylase should come back up. Phenylalanine and some other amino acids (glycine, valine, etc but not tyrosine) upregulate its activity.

interesting,many people use tyrosine for dopamine,and report good effects!

 

[NathanK]

good points .yes 1 and 5 ,prami doesnt nothing to them.i used prami for a while,biggest effect was on libido,very strong effect.it is good for mood too..

sleep attacks are manageable,simply taking it at night,and helps you sleep.its important to start prami at very low doses.i started at 50-100 mcg and it didnt give me some nasty symptoms others report about it.

i was gonna buy some prami today,but im not sure now.

i got some cabergoline in my hand,which can go for weeks.

Have you ever tried ropinirol? Ive noticed that nobody has mentioned it on the forum. It is an non ergot DA like pramipexole, but it's highest affinity is for D2 receptors.

Cabergoline and other ergoline DA give me caution since it would be a challenge to monitor the sides without a doctor. Cabergoline and pergolide (banned in USA) were shown to increase the risk of leaky heart valves by 700%.
MMS: Error

 

[paymanz]

Have you ever tried ropinirol? Ive noticed that nobody has mentioned it on the forum. It is an non ergot DA like pramipexole, but it's highest affinity is for D2 receptors.

Cabergoline and other ergoline DA give me caution since it would be a challenge to monitor the sides without a doctor. Cabergoline and pergolide (banned in USA) were shown to increase the risk of leaky heart valves by 700%.
MMS: Error

No i havent.you used it?

I think best is to use them short term as ray recommends.it could be good if we known at what dosage he advises such!

 

[NathanK]

No i havent.you used it?

I think best is to use them short term as ray recommends.it could be good if we known at what dosage he advises such!

No i havent. I had never heard of it until my doctor prescribed it the other day for my periodic limb movement disorder. After researching it, im intrigued and will probably give it a shot in the coming weeks.

The one thing im concerned about with all of these dopamine agonists is any dopamine desensitivity that could make it hard to stop or worse long term.

 

[Area-1255]

Muira Puama has dopamine D1-agonist activity. In theory you could stack it with a standard dopamine agonist medication.
That way you get balanced D1/D2 agonism.

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Phytother Res. 2009 Apr;23(4):519-24. doi: 10.1002/ptr.2664.
Antidepressant profile of Ptychopetalum olacoides Bentham (Marapuama) in mice.
Piato AL1, Rizon LP, Martins BS, Nunes DS, Elisabetsky E.
Author information

Abstract
Depression has become of universal major importance, and it is therefore vital to expand the armamentarium for treating the condition. Lack of motivation and lassitude are major symptoms treated with the use of Marapuama (Ptychopetalum olacoides, PO) remedies by communities in the Brazilian Amazon. Considering the prominence of such symptoms in depression, the present study was designed to verify the effects of a standardized PO ethanol extract (POEE) on the forced swimming (FST) and tail suspension tests (TST). POEE i.p. (15-100 mg/kg) and oral (300 mg/kg) resulted in a significant and dose-related anti-immobility effect. We further examined the involvement of dopamine, noradrenaline and serotonin in these antidepressant-like effects. POEE effects were prevented when catecholamine synthesis was inhibited by -alpha-methyl-rho-tyrosine (AMPT) (100 mg/kg, i.p.), while inhibition of serotonin synthesis with rho-chlorophenylalanine methyl ester hydrochloride (PCPA) (100 mg/kg, i.p.) was devoid of effect. The blockade of beta-adrenergic (propranolol 2 mg/kg, i.p.) and D(1) dopamine (SCH 23390 0.5 mg/kg, i.p.) receptors prevented POEE anti-immobility effects; by contrast, blockade of D(2) dopamine (sulpiride 2 and 50 mg/kg, i.p.) receptors was ineffective. Consistent with traditional use, the results indicate that POEE possesses antidepressant-like effects, possibly mediated by beta-adrenergic and D(1) dopamine receptors.

(c) 2008 John Wiley & Sons, Ltd.

PMID:

19067380

DOI:

10.1002/ptr.2664