Serotonin and gut health - Endotoxin (Lipopolysaccharride)
90% of the serotonin is produced in the gastrointestinal tract and is derived from the conversion of tryptophan amino acids. Serotonin’s other names include
thrombotonin, thrombocytin, enteramine.
[quote author=http://raypeat.com/articles/articles/serotonin-depression-aggression.shtml]“Serotonin’s other names include thrombotonin, thrombocytin, enteramine, and 5-HT, its chemical name (5-hydroxytryptamine). These historical names derive from its role in the intestine and in blood vessels. In 1951, it was discovered that enteramine and thrombotonin were a single substance, and its involvement in circulatory disease, especially hypertension and vascular spasms, was the focus of research. (The increase in the number of “cardiovascular events” recently seen in the study of women using estrogen is what might be expected from something which increases serotonin dominance.) It causes vasoconstriction and vasospasm, and promotes clotting, when it’s released from platelets. Especially when it is released from mast cells, it is considered to be an inflammatory mediator, along with histamine. Edema, bronchoconstriction, immunosuppression, and joint swelling are produced by the release of serotonin from platelets or other cells. As inflammatory mediators, serotonin and histamine are directly involved in asthma, hives, gastrointestinal damage from alcohol, nerve cell damage, edema, and shock.”
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Endotoxin is a structural component/metabolic product of most bacteria and is present in small amounts in the gut. When bacteria metabolise undigested starches and fermentable fibres, they release small amounts of endotoxin. Bacteria which die release large amounts of endotoxin.
A normal (small) amount of endotoxin plays useful physiological roles, but large amounts (10-50 times as much) can cause sepsis and even death. Smaller increases such as 2-3 times as much cause mild immune-disrupting symptoms such as the common cold or fatigue.
Endotoxin promotes the release of serotonin from platelet cells, and is allowed entry into the blood stream in increased quantities during stress (via the tight junctions in the epithelial cells aka leaky gut). High levels of endotoxin disrupts all body systems including - liver, thyroid, kidney, immune, cardiovascular etc. = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795398
Serotonin's main function in the gut is to initiate gut-movement (peristalsis) to expel waste. If there is too much serotonin (caused by too much endotoxin) - there is diarrhoea - and eventually tissue fibrosis.
[quote author=http://www.resonantfm.com/biocast-episode-12-endotoxin-serotonin-and-depression/]http://jem.rupress.org/content/114/6/857.full.pdf
EFFECTS OF BACTERIAL ENDOTOXIN ON RABBIT PLATELETS
So the first link included looks at the effect of endotoxin on rabbit blood samples.
It found that a relatively low dose of endotoxin would cause serotonin to move from the blood platelets into the blood plasma.
https://www.ncbi.nlm.nih.gov/pubmed/11458992
http://sci-hub.cc/10.1007/s007020070003
Lipopolysaccharide administration produces time-dependent and region-specific alterations in tryptophan and tyrosine hydroxylase activities in rat brain
The next study looks at the effect of endotoxin on tyrosine hydroxylase, and tryptophan hydroxylase in regions of rat brain. Tyrosine hydroxylase is the enzyme that converts the amino acid l-tyrosine to L-dopa, L-dopa is an important precursor for the neurotransmitter dopamine. Tryptophan hydroxylase is involved in the synthesis of serotonin from tryptophan. Both of these enzymes are described as the rate limiting factors in the synthesis of these neurotransmitters.
The paper cites references that demonstrated long-term isolation would increase tyrosine hydroxylase while auditory stress would increase the activation of tryptophan hydroxylase in certain parts of the brain. The paper suggests that these models of stress may look similar to the addition of endotoxin as a model of stress. Another substance that used in the experiments was NSD 1015, this is a decarboxylase inhibitor and it was used in order to prevent the destruction of the two enzymes in order that they could be measured.
The study found a significant increase in cortical and midbrain concentrations of serotonin but in the striatum their analysis showed no significant effect on serotonin. There was a significant effect on L-dopa only in the midbrain. The paper states that both enzymes are activated in response to peripheral endotoxin, varying with time and region of the brain.
The paper cites references showing increases in serotonin activity in the rat hippocampus, hypothalamus, frontal cortex ,and brainstem of rodents.
So the next paper then takes a step back to the gut and looks at the synthesis of serotonin in the colon.
http://www.cell.com/abstract/S0092-8674%2815%2900248-2
http://sci-hub.cc/10.1016/j.cell.2015.02.047
Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis
Tells us that the gastrointestinal tract contains most of the body’s serotonin but that the mechanisms are controlling serotonin synthesis were to this point unclear. The paper mentioned some of serotonins known effects on gastrointestinal diseases immune response and bone development along with cardiac function. Adult germfree mice are known to be quite the paper calls deficient in serum and plasma serotonin controls. These germfree mice have significantly lowered levels of colonic and faecal serotonin. The germfree rodents were found to have lowered levels of the tryptophan hydroxylase one enzyme, which catalyses the conversion from tryptophan to serotonin.
When a crossover of gut bacteria was performed from the germfree mice, that is they transplanted gut bacteria from conventional mice into germfree mice they found that the serum and colon levels of serotonin were increased to those seen in conventional mice. Then in an attempt to reverse the effects on serotonin the mice were giving an antibiotic treatment of four different antibiotics. Significant decreases in serotonin were seen with the antibiotics.
The paper also shows that platelets, also thrombocytes, which are a component of the blood whose function is to stop bleeding, by increasing clotting would uptake serotonin produced in the gut and delivered to sites of clotting around the body. Germfree rodents were seen to have slower clotting time be related to the levels of serotonin in the platelet from the gut. In the previous podcast I looked at endotoxin’s effects on other clotting factors possibly involved in dementia, fibrin and fibrinogen.The paper also noted that metabolites of some bacteria like
butyrate and propionate, often said to have a beneficial effect on the gut function, can increase serotonin expression, at least in a cell culture model.
http://sci-hub.cc/10.1002/jnr.490400316
Endotoxin Administration Stimulates Cerebral Catecholamine Release in Freely Moving Rats as Assessed by Microdialysis
The last paper then on the effect of endotoxin on serotonin is a study on rodents. The rodents received either endotoxin or a saline solution and had probes in various parts of their brain record markers of catecholamines, including a breakdown product of serotonin 5HIAA. It seems from my reading so far that the synthesis of serotonin or the release of serotonin from the platelet might be more important than 5H IAA in determining its potential pathological effects, however increased 5HIAA might be an indicator of increased synthesis. The paper explains that concentrations of serotonin could not be measured reliably in this model so they used 5H IAA as a proxy measurement.
They found elevations of 5H IAA in both of the brain regions that were tested, along with significant increases in norepinephrine and dopamine which peaked around two hours and returned to baseline two hours after that in one area of the brain only, the medial hypothalamus.
They also tested the effects of a non-steroidal anti-inflammatory drug called Indomethacin. This is a Cox two inhibitor, similar to aspirin in that regard and it inhibits the production of prostaglandins. Previous experiments had shown no effect from indomethacin on ACTH and corticosteroid after endotoxin treatment. Another experiment showed that indomethacin prevented the increase in catecholamines. In this experiment the indomethacin pretreatment completely prevented any increase in 5HIAA or other catecholamine or measured metabolites.
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A good article on endotoxin =
Gram Negative Bacteria and Obesity
Some of serotonin's effects:
Activation of glycolysis and suppression of mitochondrial oxidative metabolism (read the Methylene Blue thread to see the implications of this long-term)
Activation of membrane skeleton-bound phosphofructokinase in erythrocytes induced by serotonin.
We show here that serotonin, both in vivo and in vitro, induced a marked activation of phosphofructokinase, the rate-limiting enzyme in glycolysis, in the membrane-skeleton fraction from erythrocytes. Concomitantly, the hormone induced a striking increase in lactate content, reflecting stimulation of glycolysis. The enzyme’s activity in the cytosolic (soluble) fraction remained unchanged.
These results suggest a defense mechanism in the erythrocytes against the damaging effects of serotonin, whose concentration in plasma increases in many diseases and is implicated as playing an important role in circulation disturbances.
Serotonin-induced decrease in brain ATP, stimulation of brain anaerobic glycolysis and elevation of plasma hemoglobin; the protective action of calmodulin antagonists.
1.
Injection of serotonin (5-hydroxytryptamine) to rats, induced a dramatic fall in brain ATP level, accompanied by an increase in P(i). Concomitant to these changes, the activity of cytosolic phosphofructokinase, the rate-limiting enzyme of glycolysis, was significantly enhanced. Stimulation of anaerobic glycolysis was also reflected by a marked increase in lactate content in brain. 2. Brain glucose 1,6-bisphosphate level was decreased, whereas fructose 2,6-bisphosphate was unaffected by serotonin. 3. All these serotonin-induced changes in brain, which are characteristic for cerebral ischemia, were prevented by treatment with the calmodulin (CaM) antagonists, trifluoperazine or thioridazine. 4. Injection of serotonin also induced a marked elevation of plasma hemoglobin, reflecting lysed erythrocytes, which was also prevented by treatment with the CaM antagonists. 5. The present results suggest that CaM antagonists may be effective drugs in treatment of many pathological conditions and diseases in which plasma serotonin levels are known to increase.
Serotonin stimulates mouse skeletal muscle 6-phosphofructo-1-kinase through tyrosine-phosphorylation of the enzyme altering its intracellular localization.
Serotonin (5-HT) is a hormone implicated in the regulation of many physiological and pathological events. One of its most intriguing properties is the ability to up-regulate mitosis. Moreover, it has been shown that 5-HT stimulate glucose uptake on skeletal muscle, suggesting that 5-HT may regulate glucose metabolism of peripheric tissues.
...
Altogether, our results support evidences that 5-HT augments skeletal muscle glucose consumption through stimulation of glycolysis key regulatory enzyme, PFK, throughout tyrosine phosphorylation and intracellular redistribution of the enzyme.
Serotonin can reduce the production of energy by inhibiting mitochondrial respiratory enzymes (Medvedev, 1990, 1991), and by reduction of oxygen delivery to tissues by vasoconstriction. It also appears to interfere with the use of glucose (de Leiva, et al., 1978, Moore, et al., 2004).
The primary mediator of Fibrosis:
Serotonin paracrine signaling in tissue fibrosis.
The molecule serotonin (5-hydroxytryptamine or 5-HT) is involved in numerous biological processes both inside and outside of the central nervous system. 5-HT signals through 5-HT receptors and it is the diversity of these receptors and their subtypes that give rise to the varied physiological responses.
It is clear that platelet derived serotonin is critical for normal wound healing in multiple organs including, liver, lung heart and skin. 5-HT stimulates both vasoconstriction and vasodilation, influences inflammatory responses and promotes formation of a temporary scar which acts as a scaffold for normal tissue to be restored. However, in situations of chronic injury or damage 5-HT signaling can have deleterious effects and promote aberrant wound healing resulting in tissue fibrosis and impaired organ regeneration. This review highlights the diverse actions of serotonin signaling in the pathogenesis of fibrotic disease and explores how modulating the activity of specific 5-HT receptors, in particular the 5-HT2 subclass could have the potential to limit fibrosis and restore tissue regeneration. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease.
Wikipedia article for Turgeride medication
"..
.Serotonin stimulates the proliferation of pulmonary artery smooth muscle cells, and induces fibrosis in the wall of pulmonary arteries. Together, this causes vascular remodeling and narrowing of the pulmonary arteries. These changes result in increased vascular resistance and PAH. Due to the potential anti-proliferative and anti-fibrotic activity of terguride, this potential medicine could offer the hope of achieving reversal of pulmonary artery vascular remodeling and attenuation of disease progression."
Serotonin is elevated in multiple pathological conditions
Role of serotonin in the pathophysiology of the irritable bowel syndrome
Altered 5-HT signalling may lead to both intestinal and extraintestinal symptoms in IBS. 5-HT directly and indirectly affects intestinal motor and secretory function and abnormalities may lead to either constipation or diarrhea. 5-HT modulates sensation and perception of visceral stimulation at peripheral and central sites. Therapeutic agents targeting altered 5-HT signalling may provide new, effective treatments for patients with IBS.
The Role of 5-HT Dysregulation in Inflammatory Bowel Disease
Serotonin and GI Disorders: An Update on Clinical and Experimental Studies
The regulation of 5-HT- and 5-HT-expressing EC cells is intimately associated with the inflammatory processes that drive many GI disorders. Recent studies on EC cells and 5-HT have generated a number of concepts that provide insight into how the immune and endocrine systems of the gut interface.
It is evident from these studies that mediators from immune cells such as cytokines have an important role in EC cell biology and production of 5-HT in the gut. In addition, 5-HT has a key role in the pathogenesis of experimental colitis and in generation of pro-inflammatory mediators from immune cells. If this is not complex enough, this entire relationship is occurring in the presence of varying diets and mediators secreted by the microbiota, which may directly or indirectly influence the EC cell function.
Recently, Margolis et al.75 has shown that inhibition of 5-HT synthesis using a specific inhibitor of the TpH1 enzyme reduces the severity of trinitrobenzene sulfonic acid-induced colitis in mice. This finding furthers supports our observation that 5-HT is a critical molecule in pathogenesis of colitis and suggest that targeted inhibition of 5-HT synthesis may ultimately help in the development of improved therapeutic strategies in GI inflammatory disorders.
The serotonin system in autism spectrum disorder: From biomarker to animal models.
Elevated whole blood serotonin, or hyperserotonemia, was the first biomarker identified in autism spectrum disorder (ASD) and is present in more than 25% of affected children. The serotonin system is a logical candidate for involvement in ASD due to its pleiotropic role across multiple brain systems both dynamically and across development. Tantalizing clues connect this peripheral biomarker with changes in brain and behavior in ASD, but the contribution of the serotonin system to ASD pathophysiology remains incompletely understood. Studies of whole blood serotonin levels in ASD and in a large founder population indicate greater heritability than for the disorder itself and suggest an association with recurrence risk. Emerging data from both neuroimaging and postmortem samples also indicate changes in the brain serotonin system in ASD. Genetic linkage and association studies of both whole blood serotonin levels and of ASD risk point to the chromosomal region containing the serotonin transporter (SERT) gene in males but not in females. In ASD families with evidence of linkage to this region, multiple rare SERT amino acid variants lead to a convergent increase in serotonin uptake in cell models. A knock-in mouse model of one of these variants, SERT Gly56Ala, recapitulates the hyperserotonemia biomarker and shows increased brain serotonin clearance, increased serotonin receptor sensitivity, and altered social, communication, and repetitive behaviors. Data from other rodent models also suggest an important role for the serotonin system in social behavior, in cognitive flexibility, and in sensory development. Recent work indicates that reciprocal interactions between serotonin and other systems, such as oxytocin, may be particularly important for social behavior. Collectively, these data point to the serotonin system as a prime candidate for treatment development in a subgroup of children defined by a robust, heritable biomarker.
An overlooked connection: serotonergic mediation of estrogen-related physiology and pathology
Most research on pathologies in women's health has centered on changes in E2.
Our review of data from a variety of fields suggests that serotonin is one way that estrogen is exerting its effects on physiology and pathology in women. The primary function of E2 is reproductive, and serotonergic mediation of the estrogen system likely provides reproductive benefits that are not yet understood. Several of the effects we have discussed could produce reproductive benefits: immune suppression during pregnancy could decrease the chance of lost pregnancies, postpartum activation of the immune system could increase antibodies in milk, increased clotting and vasoconstriction in the uterus could prevent bleeding during birth, and increased available calcium during lactation could improve the quality of breast milk.
Notably, the same mechanism that results in these potential benefits in the reproductive system also produces changes in the remainder of the body that have consequences for women's physiology and pathologies. Whether the potential reproductive benefit of these effects is adequate to account for the maintenance of the estrogen/serotonin link remains to be explored. We suggest serotonergic mediation might contribute to explaining E2's effects on some pathologies, including heart attacks, multiple sclerosis, and breast cancer. Altering specific aspects of the serotonergic system, rather than simply increasing E2, could allow clinicians to target treatments in particular tissues or towards particular receptor types, alleviating undesirable side effects of E2 administration. Further studies are needed in order to unmask the precise molecular relationship between estrogen and serotonin and to document the clinical applications of this putative relationship.
for some information on estrogen see:
The Health and Wellness Show - Keeping it Rill about the Pill
Increased levels of free serotonin in plasma of symptomatic asthmatic patients.
RESULTS:
The clinical severity rating and levels of free serotonin, norepinephrine, epinephrine, dopamine, and cortisol were significantly higher in symptomatic asthmatic patients than those in asymptomatic patients (P < .001, in all cases). FEV1 was significantly lower in symptomatic patients than in asymptomatic patients. In symptomatic patients, the level of free serotonin correlated positively with the clinical severity rating (r = .564, P < .01) and negatively with FEV1 (r = -.959, P < .001). In addition, the clinical severity rating showed a negative correlation with FEV1 (r = -.359, P < .01). No significant correlations were found in asymptomatic patients.
CONCLUSION:
Our finding that free serotonin was the only neuroendocrine factor closely associated with clinical severity and pulmonary function suggests that this factor plays an important role in the pathophysiology of acute asthma.
Serotonin modulates the cytokine network in the lung: involvement of prostaglandin E2
Serotonin, well known for its role in depression, has been shown to modulate immune responses.
Interestingly, the plasma level of serotonin is increased in symptomatic asthmatic patients and the use of anti-depressants, known to reduce serotonin levels, provokes a decrease in asthma symptoms and an increase in pulmonary function. Thus, we tested the hypothesis that serotonin affects alveolar macrophage (AM) cytokine production, altering the cytokine network in the lung and contributing to asthma pathogenesis. AMs were treated with different concentrations of serotonin (10-11−10-9 M) or 5-HT1 and 5-HT2 receptor agonists for 2 h prior stimulation. T helper 1 (Th1) and Th2 cytokines, prostaglandin-E2 (PGE2) and nitric oxide (NO) were measured in cell-free supernatants.
Serotonin significantly inhibited the production of tumour necrosis factor (TNF) and interleukin (IL)-12, whereas IL-10, NO and PGE2 production were increased. These immunomodulatory effects of serotonin were mimicked by 5-HT2 receptor agonist but were not abrogated by 5-HT2 receptor antagonist, suggesting the implication of other 5-HT receptors.
Inhibitors of cyclooxygenase and antibody to PGE2 abrogated the inhibitory and stimulatory effect of serotonin on TNF and IL-10 production, respectively, whereas NO synthase inhibitor eliminated serotonin-stimulated IL-10 increase. Furthermore, PGE2 significantly increased AM IL-10 and NO production. These results suggest that serotonin alters the cytokine network in the lung through the production of PGE2. The reduction of Th1-type cytokine by serotonin may contribute to asthma pathogenesis.
Elevated serotonin and reduced dopamine in subregionally divided Huntington's disease striatum.
We measured the rostrocaudal distribution of serotonin, dopamine, and their metabolites in Huntington's disease striatum (caudate and putamen). Mean levels of serotonin or 5-hydroxyindoleacetic acid were elevated in most striatal subdivisions, whereas concentrations of dopamine or its metabolite homovanillic acid were slightly to markedly reduced. Dopamine and serotonin were at control levels in the nucleus accumbens and substantia nigra. Whereas the above-normal serotonin can most likely be accounted for by striatal atrophy, the reduced dopamine suggests either a marked down-regulation of nigrostriatal dopamine neurons or an actual reduction in the arborization of the striatal dopamine neurons.
As experimental animal data suggest, the relative excess of striatal serotonin or one of its metabolites may facilitate the neurodegenerative process in Huntington's disease striatum.
Clopidogrel Treatment in Scleroderma Patients Shown to Induce Digital Ulcers - Scleroderma News
"...Recent research has suggested that patients with scleroderma might have abnormal activation of their blood platelets, caused by the damage to blood vessels that characterize the disease. Several platelet-linked molecules are increased in the blood of patients, and an earlier study showed that the release of serotonin, caused by platelet activation, might induce skin fibrosis in experimental animals. The data have led researchers to hypothesize that fibrosis is the result of a chain of events, starting with dysfunctional endothelial cells — forming the lining of blood vessels — over platelet activation, serotonin release and activation of fibrosis producing fibroblasts."
Pregnant rats treated with a serotonin precursor have reduced fetal weight and lower plasma volume and kallikrein levels.
Pregnant women with preeclampsia have increased serotonin levels, suggesting a possible role of this amine in abnormal pregnancy. With the hypothesis that an increase in serotonin would reduce volume expansion and cause fetal growth restriction, we evaluated the maternal and fetal effects of the administration of the serotonin precursor 5-hidroxytryptophan (5-HTP) to Sprague-Dawley rats. At pregnancy day 13 (n=19) or in random cycle nonpregnant rats (n=10), animals were assigned to a single injection of 5-HTP (100 mg/kg IP) or to a control group. Animals were studied at day 21, after overnight urinary collection. Additional pregnant rats received ketanserin (1 mg/kg), a 5-HT(2) receptor antagonist, 1 hour before 5-HTP injection. In pregnant rats, 5-HTP lowered plasma volume (control: 22+/-1.1; 5-HTP: 17+/-0.7 mL; P<0.001) and creatinine clearance, whereas serum creatinine and urinary protein excretion were increased; no changes were observed in nonpregnant rats. Systolic blood pressure did not change significantly. Urinary kallikrein activity and plasma aldosterone levels decreased only in pregnant animals. Fetal (control: 5.5+/-0.1; 5-HTP: 4.2+/-0.2 g; P<0.001) and placental weights were reduced.
In nonpregnant and pregnant animals, 5-HTP caused profound renal morphological alterations and decreased kallikrein immunostaining. Preadministration of ketanserin abolished all of the changes associated with the use of 5-HTP. These data indicate that the administration of a serotonin precursor to pregnant rats limits plasma volume expansion and fetal growth via 5-HT(2) receptors, suggesting a possible role for serotonin in abnormal pregnancy. We postulate that an increased vascular resistance, both at the placental and renal levels, mediates these effects.
Anti serotonin drugs treat various serotonin-mediated pathology
Effects of antidepressant mirtazapine on fibromyalgia symptoms.
PURPOSE:
Fibromyalgia syndrome (FS) is a form of non-articular rheumatism. The main criteria are the widespread musculoskeletal pain and tender points at multiple characteristic sites which are associated with several vegetative and functional symptoms. Depression is the most frequent psychiatric concomitant of FS. Etiology is unknown, connection between disturbances of serotonin metabolism and pathogenesis is postulated. Pharmacological therapy with analgetic and nonsteroidal antiinflammatory drugs is not very effective. Positive effects were reported in some patients treated with antidepressant drugs, especially serotonergic agents.
MATERIAL AND METHODS:
In the study a novel antidepressant drug mirtazapine was used characterized by selective blockade of 5-HT2 and 5-HT3 receptors. In an open trial participated 29 patients with FS, who met 1990 ACR criteria for fibromyalgia. All were treated with mirtazapine for 6 weeks. Intensity of pain, sleep disturbances, fatigue and other symptoms were measured using visuale analogue scale, severity of depression was evaluated with HDRS and BDI.
RESULTS:
An open trial completed 26 patients, the majority of them experienced a clinical improvement at the end of the study as a consequence of > or = 40% reduced intensity of fibromyalgia symptoms as well as reduced severity of depression. The significant correlation between reduction in depression after 6 weeks of mirtazapine treatment with the reduction on all four main symptoms of FS suggests a common pathophysiology of depression and symptoms of fibromyalgia. The data thus far obtained indicate the blockade of 5-HT2 and 5-HT3 receptors with mirtazapine as an effective and promising method in FS.
CONCLUSIONS:
Further double-blind placebo-controlled study are required to confirm our results.
LX-1031, a Tryptophan 5-hydroxylase Inhibitor, and Its Potential in Chronic Diarrhea Associated with Increased Serotonin
Background
LX-1031 is an oral, small-molecule tryptophan 5-hydroxylase (TPH) inhibitor that reduces serotonin (5-HT) synthesis peripherally. It has potential for illnesses characterized by excess 5-HT, such as diarrhea-predominant irritable bowel syndrome (IBS-D) and carcinoid diarrhea. In vitro, inhibition of TPH1 occurred in 10−8 – 10−7 M range. In vivo in rodents, LX-1031 has no effect on brain 5-HT while dose-dependently reducing 5-HT, particularly in the small bowel.
Conclusion
LX-1031 appears promising for chronic diarrhea associated with increased 5-HT expression including IBS-D. Optimal doses, efficacy and safety in IBS clinical trials need to be fully elucidated; low systemic exposure, selectivity for TPH1 over TPH2, and lack of effect on brain 5-HT in several species suggest that LX-1031 is unlikely to cause affective disorders.
Cyproheptadine: An anti-serotonin + anti-histamine compound
Taken from
one post by haidut on the Raypeatforum:
1. Cyproheptadine may have strong anti-cancer properties:
http://www.ncbi.nlm.nih.gov/pubmed/23076705
http://www.ncbi.nlm.nih.gov/pubmed/18502826
2. Cyproheptadine may treat autism:
http://www.ncbi.nlm.nih.gov/pubmed/15068403
http://www.ncbi.nlm.nih.gov/pubmed/12231270
3. Cyproheptadine may treat schizophrenia. This raises serious questions if schizophrenia is "caused by excessive dopamine" as the current mainstream dogma holds since cyproheptadine would in theory increase dopamine and its effects:
http://www.ncbi.nlm.nih.gov/pubmed/11728834
http://www.ncbi.nlm.nih.gov/pubmed/10319907
4. Cyproheptadine may treat depression and other similar mental issues:
http://www.ncbi.nlm.nih.gov/pubmed/7667171
http://www.ncbi.nlm.nih.gov/pubmed/23442031
http://www.ncbi.nlm.nih.gov/pubmed/9304415
5. Cyproheptadine may be heart-protective (Ray said that anti-serotonin drugs like ondansetron protect the heart):
http://www.ncbi.nlm.nih.gov/pubmed/19346455
http://www.ncbi.nlm.nih.gov/pubmed/7976381
6. Cyproheptadine may protect the brain from the damage caused by BOTH ischemic and hemorrhagic stroke:
http://www.ncbi.nlm.nih.gov/pubmed/7976376
http://www.ncbi.nlm.nih.gov/pubmed/1757225
http://www.ncbi.nlm.nih.gov/pubmed/3982650
7. Cyproheptadine may protect the brain in a very generalized way by increasing cholesterol and phospholipids:
http://www.ncbi.nlm.nih.gov/pubmed/8225552
8. Cyproheptadine may protect from endotoxin:
http://www.ncbi.nlm.nih.gov/pubmed/11940385
http://www.ncbi.nlm.nih.gov/pubmed/1598825
http://www.ncbi.nlm.nih.gov/pubmed/8368073
9. Cyproheptadine may stimulate the immune system:
http://www.ncbi.nlm.nih.gov/pubmed/3567337
10. Cyproheptadine may have anti-endorphin action similar to naltrexone:
http://www.ncbi.nlm.nih.gov/pubmed/2995088
11. Cyproheptadine may suppress prolactin, growth hormone, aldosterone, ACTH, TSH, and cortisol:
http://www.ncbi.nlm.nih.gov/pubmed/2994332
http://www.ncbi.nlm.nih.gov/pubmed/6109449
http://www.ncbi.nlm.nih.gov/pubmed/7017408
http://www.ncbi.nlm.nih.gov/pubmed/115197
http://www.ncbi.nlm.nih.gov/pubmed/4600047
http://www.ncbi.nlm.nih.gov/pubmed/177441
http://www.ncbi.nlm.nih.gov/pubmed/177112
http://www.ncbi.nlm.nih.gov/pubmed/1201741
http://www.ncbi.nlm.nih.gov/pubmed/180050
http://www.ncbi.nlm.nih.gov/pubmed/401824
12. Cyproheptadine may suppress prostaglandin synthesis and effects (similar to aspirin):
http://www.ncbi.nlm.nih.gov/pubmed/412631
http://www.ncbi.nlm.nih.gov/pubmed/508004
13. Cyproheptadine may be helpful in the treatment of "alcoholism":
http://www.ncbi.nlm.nih.gov/pubmed/3797491
http://www.ncbi.nlm.nih.gov/pubmed/14157085
14. Cyproheptadine may be helpful in the treatment of "psoriasis":
http://www.ncbi.nlm.nih.gov/pubmed/6735444
15. Cyproheptadine may be helpful in the treatment of decompression sickness:
http://www.ncbi.nlm.nih.gov/pubmed/7233624
16. Cyproheptadine may be helpful in restoring fertility in old age:
http://www.ncbi.nlm.nih.gov/pubmed/1204806
17. Cyproheptadine may be helpful in treating myopathy (muscle weakness):
http://www.ncbi.nlm.nih.gov/pubmed/4274414
