Urinary Excretion Of Serotonin Research Articles

Nutūl as an effective and time tested regimenal modality in Unani system of medicine: An Overview

Ilāj bit tadbīr is one of the treatment plans in the Unani system of medicine which includes the modification in asbāb-i-sitta zarooriya (six essential factors) through certain interventions. Nutūl or irrigation is a classical and effective method in regimenal therapy which refers to pouring or dripping of liquid slowly and steadily over the body part from a pre-fixed height. The benefits achieved are an amalgamation of neurological effect, psychological effect and pharmacological actions of the procedure and the drugs used. For this purpose, usually water, oil or medicated decoction is poured from a height over specific sites of body in certain diseases. Therapeutically, nutūl is effective in various ways such as dispersing the causative morbid matter from the part, normalizing the mal-temperament, relieving pain, increasing the circulation, etc. It is specifically useful as an adjuvant treatment in the management of central nervous system disorders like headache, insomnia, migraine, amnesia, melancholia, vertigo, epilepsy and also in certain other disorders like cystitis, mastitis, arthralgia, etc. These therapeutic effects are expected due to the kafiyat (quality) of liquid and the constituents of the formulation used in the procedure. Nutūl has an analgesic effect also, hence, recommended in several Musculoskeletal problems such as waja-ul-mafasil (osteoarthritis), waja-uz-zahr (low backache), waja-ul-azlat (myalgia), irq-un-nasa (sciatica), etc. The exact mechanism of action of Nutūl therapy is still not known but few preliminary reports suggested that it has an anxiolytic effect through decreasing the plasma noradrenaline and urinary serotonin excretion, decrease in rate of breathing, reduction in diastolic blood pressure and heart rate with lowered sympathetic tone.
 Keywords: Taḥlīl; Kafiyat; Mizāj; Tadbīr; Joshānda

Both Stimulatory and Inhibitory Effects of Dietary 5-Hydroxytryptophan and Tyrosine are Found on Urinary Excretion of Serotonin and Dopamine in a Large Human Population [Retraction

[This retracts the article DOI: 10.2147/NDT.S5040.].

Both Stimulatory and Inhibitory Effects of Dietary 5-Hydroxytryptophan and Tyrosine are Found on Urinary Excretion of Serotonin and Dopamine in a Large Human Population [Expression of Concern

Both Stimulatory and Inhibitory Effects of Dietary 5-Hydroxytryptophan and Tyrosine are Found on Urinary Excretion of Serotonin and Dopamine in a Large Human Population [Expression of Concern

Neurobiological and clinical variables associated with alcohol abuse in bulimia nervosa.

The study was aimed at analysing the reciprocal relationships of several clinical and neurobiological items in order to predict alcohol misuse in patients with bulimia nervosa (BN). Seventy BN patients and 70 healthy controls were assessed for depression, impulsivity, borderline personality traits and self-defeating behaviours using specific scales; serum cortisol and 24-hour urinary excretion of serotonin and 5-hydroxiindolacetic acid were also assessed. The study confirmed the implications of these clinical factors for alcohol misuse in BN patients, but the results suggested that depressive symptoms and hypercortisolism could lie behind these relationships.

Time-dependent effects of L-tryptophan administration on urinary excretion of L-tryptophan metabolites.

We have previously reported that dietary supplementation with up to 5.0 g/d of L-tryptophan (L-Trp) for 21 d has no adverse effects, judging from the levels of general blood variables, in healthy women. We performed a randomized, double-blind, placebo-controlled, crossover intervention study in 17 apparently healthy Japanese women. The subjects were randomly assigned to receive a placebo (0 g/d) or 1.0, 2.0, 3.0, 4.0, or 5.0 g/d of L-Trp for 21 d each with a 5-wk washout period between trials. We examined the 24-h urine profiles on days -1 (1 d before starting L-Trp), 7, 14, and 21 to determine whether administration of L-Trp at doses of up to 5.0 g/d affects time-dependent urinary excretion of L-Trp or its metabolites in healthy women. The urinary excretion of L-Trp, kynurenic acid, 3-hydroxykynurenine, xanthurenic acid, 3-hydroxyanthranilic acid, quinolinic acid, N(1)-methylnicotinamide, N(1)-methyl-2-pyridone-5-carboxamide, and N(1)-methyl-4-pyridone-3-carboxamide increased in an L-Trp dose-dependent manner on day 7. The amount of urinary excretion of these compounds was unchanged on days 14 and 21. The urinary excretion of serotonin, 5-hydroxyindole-3-acetic acid, 2-oxoadipic acid, and nicotinamide was unaffected by L-Trp at any of the doses tested. L-Trp doses had weak effects on the urinary excretion of kynurenine and anthranilic acid. Based on these findings, we conclude that there are no time-dependent effects of L-Trp administration in urinary excretion of L-Trp metabolites. Additionally, L-Trp and its metabolites do not accumulate in the body.

Evaluation of a novel ELISA for serotonin: urinary serotonin as a potential biomarker for depression

Depression is a common disorder with physical and psychological manifestations often associated with low serotonin. Since noninvasive diagnostic tools for depression are sparse, we evaluated the clinical utility of a novel ELISA for the measurement of serotonin in urine from depressed subjects and from subjects under antidepressant therapy. We developed a competitive ELISA for direct measurement of serotonin in derivatized urine samples. Assay performance was evaluated and applied to clinical samples. The analytical range of the assay was from 6.7 to 425 μg serotonin/g creatinine (Cr). The limit of quantification was 4.7 μg/g Cr. The average recovery for spiked urine samples was 104.4%. Average intra-assay variation was 4.4%, and inter-assay variation was <20%. The serotonin analysis was very specific. No significant interferences were observed for 44 structurally and nonstructurally related urinary substances. Very good correlation was observed between urinary serotonin levels measured by ELISA and liquid chromatography tandem mass spectrometry (LC-MS/MS; ELISA = 1.16 × LC-MS/MS - 53.8; r = 0.965; mean % bias = 11%; n = 18). Serotonin was stable in acidified urine for 30 days at room temperature and at -20 °C. The established reference range for serotonin was 54-366 μg/g Cr (n = 64). Serotonin levels detected in depressed patients (87.53 ± 4.89 μg/g Cr; n = 60) were significantly lower (p < 0.001) than in nondepressed subjects (153.38 ± 7.99 μg/g Cr). Urinary excretion of serotonin in depressed individuals significantly increased after antidepressant treatment by 5-hydroxy-tryptophane and/or selective serotonin re-uptake inhibitor (p < 0.01). The present ELISA provides a convenient and robust method for monitoring urinary serotonin. It is suitable to monitor serotonin imbalances and may be particularly helpful in evaluating antidepressant therapies.

Both stimulatory and inhibitory effects of dietary 5-hydroxytryptophan and tyrosine are found on urinary excretion of serotonin and dopamine in a large human population

Amino acid precursors of dopamine and serotonin have been administered for decades to treat a variety of clinical conditions including depression, anxiety, insomnia, obesity, and a host of other illnesses. Dietary administration of these amino acids is designed to increase dopamine and serotonin levels within the body, particularly the brain. Convincing evidence exists that these precursors normally elevate dopamine and serotonin levels within critical brain tissues and other organs. However, their effects on urinary excretion of neurotransmitters are described in few studies and the results appear equivocal. The purpose of this study was to define, as precisely as possible, the influence of both 5-hydroxytryptophan (5-HTP) and tyrosine on urinary excretion of serotonin and dopamine in a large human population consuming both 5-HTP and tyrosine. Curiously, only 5-HTP exhibited a marginal stimulatory influence on urinary serotonin excretion when 5-HTP doses were compared to urinary serotonin excretion; however, a robust relationship was observed when alterations in 5-HTP dose were compared to alterations in urinary serotonin excretion in individual patients. The data indicate three statistically discernible components to 5-HTP responses, including inverse, direct, and no relationships between urinary serotonin excretion and 5-HTP doses. The response to tyrosine was more consistent but primarily yielded an unexpected reduction in urinary dopamine excretion. These data indicate that the urinary excretion pattern of neurotransmitters after consumption of their precursors is far more complex than previously appreciated. These data on urinary neurotransmitter excretion might be relevant to understanding the effects of the precursors in other organs.

Psychoneuroimmunologic Effects of Ayurvedic Oil-Dripping Treatment

This study assessed the psychoneuroimmunologic changes achieved by Shirodhara, an Ayurvedic treatment, characterized by dripping oil on the forehead, in a randomized, controlled protocol involving a novel approach using a robotic system. In the first experiment for the determination of the most appropriate conditions of Shirodhara, 16 healthy females (33 +/- 9 years old) underwent a 30-minute treatment. In the second study, another 16 healthy females (39 +/- 9 years old) were assigned to either the Shirodhara treatment or control supine position for 30 minutes, with monitoring of physiologic, biochemical, immunologic, and psychometric parameters including anxiety and altered states of consciousness (ASC). The subjects receiving Shirodhara treatment showed lowered levels of state anxiety and higher levels of ASC than those in the control position. Plasma noradrenaline and urinary serotonin excretion decreased significantly more after Shirodhara treatment than in the control. Plasma levels of thyrotropin-releasing hormone, dopamine, and natural killer (NK) cell activity were different between control and Shirodhara treatment. The correlation between anxiolysis and the depth of ASC was significant in the Shirodhara treatment group (r = 0.52, p < 0.05, N = 16), while in the control no correlation was obtained (r = 0.13, p = 0.64, N = 16). The increase in foot skin temperature after Shirodhara showed a significant correlation with anxiolysis and the depth of Trance of ASC (r = 0.58, p < 0.01, r = 0.43, p < 0.01, respectively). NK cell activity after Shirodhara treatment showed a significant correlation with anxiolysis and the depth of Trance of ASC (r = 0.33, p < 0.05, r = 0.56, p < 0.01, respectively). These results indicate that Shirodhara has anxiolytic and ASC-inducing effects, and it promotes a decrease of noradrenaline and exhibits a sympatholytic effect, resulting in the activation of peripheral foot skin circulation and immunopotentiation.

Intrarenal serotonin, dopamine, and phosphate handling in remnant kidneys

Serotonin (5-HT) and dopamine (DA) are intrarenal autocrine/paracrine substances that regulate phosphate reabsorption. The present studies explored intrarenal serotonin and DA metabolism and the implications for phosphate homeostasis in rats with remnant kidneys, a model for renal failure. The intrarenal productions of serotonin and DA were determined from measurements of renal interstitial fluid (microdialysate) and urine in rats with remnant or intact kidneys. In clearance studies, the effects of infusion of methiothepin, a serotonin receptor antagonist, or gludopa, a renal selective DA precursor, on phosphate and sodium excretion were determined in rats with a remnant or intact kidneys. Renal interstitial serotonin (5-HT, 3.4 +/- 0.9 pg/min) was fourfold higher than DA (0.6 +/- 0.1 pg/min) in remnant kidneys. Conversely, urinary excretion of serotonin was fourfold less than DA in rats with a remnant kidney (5-HT 0.4 +/- 0.02 vs. DA 1.5 +/- 0.1 ng/min). Infusion of methiothepin or gludopa significantly increased the fractional excretion of phosphate (FE(Pi)) in rats with a remnant kidney from 54 +/- 3 to 67 +/- 7% (P < 0.05) and from 36 +/- 10% to 51 +/- 13% (P < 0.05), respectively. We conclude that serotonin preferentially accumulates in the renal interstitium, whereas DA exits primarily via the tubular lumen. Phosphate excretion is increased by both the acute infusion of the serotonin receptor antagonist and the infusion of gludopa, suggesting that both serotonin and DA modulate phosphate excretion in rats with remnant kidneys.

Relationship of Urinary Serotonin Excretion to Cigarette Smoking and Respiratory Symptoms: The Normative Aging Study

The relationship of 2-h urinary excretion of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) to cigarette smoking and respiratory symptoms was examined among 631 male participants in the Normative Aging Study (age range, 44 to 85 years). The amount of serotonin excreted in urine was inversely related to age (p less than 0.001). Mean 2-h excretion of serotonin varied from 8.01 micrograms for men 40 to 49 years of age to 5.84 micrograms for those 70 years of age or over. No clear relationship was evident between the amount of 5-HIAA excreted in urine and age. After adjustment for age, current smokers were found to excrete more serotonin (p less than 0.001) and 5-HIAA (p = 0.001) than never smokers. Former smokers did not differ significantly from never smokers in these respects. After adjustment for age and smoking status in a multivariate model, chronic cough was a significant predictor of serotonin excretion (p = 0.005); chronic cough was less predictive of 5-HIAA excretion (p = 0.07). Other respiratory symptoms were unrelated to urinary excretion of serotonin and 5-HIAA. The mechanisms underlying the observed relationships of urinary serotonin and 5-HIAA excretion to smoking and to chronic cough and their potential relevance to chronic bronchitis remain to be determined.

Reduced urinary serotonin excretion after intake of high doses of hypoxanthine.

Two healthy volunteers were treated with hypoxanthine 3 x 1 g and allopurinol 3 x 100 mg daily for 1 week. During this treatment serum oxypurine concentration and urinary oxypurine excretion increased as expected. No side effects were observed except for some mild daytime drowsiness and lethargy. Measurements of urinary serotonin (5-HT) excretion showed decreases to as much as 60% below initial values. Decreased urinary 5-HT excretion was also found in a patient with incomplete Lesch-Nyhan syndrome during treatment with high doses of hypoxanthine. His neurological symptoms improved slightly. The results suggest that high doses of hypoxanthine exert a nonspecific sedative effect on both patients with Lesch-Nyhan syndrome and healthy controls. The cause is probably a reduced synthesis or release of 5-HT.

High-performance liquid-chromatographic analysis for serotonin and tryptamine excreted in urine after oral loading with L-tryptophan.

We describe a method used for determining serotonin and tryptamine in urine after oral loading with their precursor amino acid. Several factors affecting prepurification and chromatographic separation of both indoleamines were optimized, including sample extraction and mobile-phase composition. Under optimal conditions, serotonin and tryptamine are extracted from urine samples together with an internal standard, and then they are separated by reversed-phase chromatography followed by native fluorescence detection. The analytical procedure is simple enough to apply to routine analysis and performable at low cost. Sensitivity and selectivity of the method are satisfactory enough to determine urinary serotonin and tryptamine. By pursuing urinary excretion of serotonin and tryptamine after oral loading with L-tryptophan (30 mg per kilogram body weight), our method proves that urinary excretion of both indoleamines increases immediately after loading and reaches a maximum in about 45 min.

Effect of nasal allergen challenge on serotonin, substance P and vasoactive intestinal peptide in plasma and nasal secretions

We have studied the changes in concentration of serotonin, substance P, and vasoactive intestinal peptide (VIP) in plasma following a nasal allergen provocation in 14 grass pollen-allergic subjects; in five the urinary excretion of serotonin and 5-hydroxy-indolyl-acetic acid (5-HIAA) was also measured. In addition, the concentration of serotonin and substance P was measured in nasal secretions following nasal challenge with allergen and methacholine. The results showed an allergen-induced increase in free plasma serotonin (P less than 0.01) and no change in platelet serotonin, urinary serotonin and urinary 5-HIAA. The plasma substance P level tended to fall (P greater than 0.1), while plasma VIP increased significantly (P less than 0.02). In nasal secretions, there were measurable levels of serotonin in all samples and of substance P in all but one. There was no difference between the concentrations of serotonin and substance P in secretions collected after allergen challenge and after methacholine challenge. For both substances, the secretion median value was comparable to that of plasma. Symptom reduction by topical and systemic pretreatment with a serotonin- and VIP-antagonist before nasal allergen provocation is necessary to define the role of these two agents in allergic rhinitis.

Urinary serotonin in the diagnosis of carcinoid tumors.

To determine whether measurement of serotonin in urine would give useful complementary information to the usual measurement of 5-hydroxyindoleacetic acid (5-HIAA) in urine and platelet serotonin in platelets, I measured these analytes in 75 consecutive patients with carcinoid tumors, and found that 75% had above-normal urinary 5-HIAA excretion, 64% had above-normal serotonin excretion, and 64% had above-normal platelet serotonin concentration. Six patients had increased urinary serotonin, but 5-HIAA excretion and platelet serotonin concentration were normal. Only two of a further 50 patients with solid noncarcinoid tumors--and none of 55 patients with flushing or diarrhea, who did not prove to have a carcinoid tumor--had increased urinary serotonin. Ingestion of four bananas (a food rich in serotonin) increased urinary 5-HIAA but not urinary serotonin excretion of seven normal subjects. Evidently, measurement of urinary serotonin excretion is helpful in the evaluation of patients with suspected carcinoid tumors.

Formation of serotonin by rat kidneys in vivo.

Renal formation of serotonin by decarboxylation of its amino acid precursor L-5-hydroxytryptophan (L-5-HTP) has been demonstrated with renal tissue homogenates and isolated perfused rat kidneys. Our objective in the present study was to determine whether the conversion of L-5-HTP to serotonin was associated with functional changes by kidneys in vivo. Renal clearance studies were conducted in anesthetized, volume-expanded male Sprague-Dawley rats receiving either saline (n = 9) or L-5-HTP (15 and 75 micrograms/min iv, n = 9). No change in mean arterial pressure was measured during infusions of L-5-HTP at either dose, whereas glomerular filtration rate (GFR), as measured by the clearance of inulin, and effective renal plasma flow (CPAH) decreased by 34 +/- 5% (mean +/- SE, P less than 0.001) and 26 +/- 7% (P greater than 0.07), respectively. Urine flow and sodium excretion decreased by 41 +/- 9% (P less than 0.01). Serotonin and 5-HTP were determined in urine and plasma using HPLC. High levels of 5-HTP were present in plasma, but not urine. Urinary serotonin increased in the rats receiving L-5-HTP without concomitant increases in plasma serotonin. More than 20% of the infused L-5-HTP was recovered in the urine as serotonin. The decarboxylase inhibitor carbidopa (20 micrograms/min) markedly reduced urinary serotonin excretion in the rats which received L-5-HTP and reversed the changes in GFR, CPAH, urine flow, and sodium excretion. Infusions of the amino acid precursor of L-5-HTP, L-tryptophan (n = 7), did not alter kidney function or increase plasma or urinary 5-HTP or serotonin levels. These results are consistent with the intrarenal formation of serotonin by renal decarboxylase with attendant alterations in renal hemodynamics and salt and water excretion.

Serotonin metabolism and depression in oral contraceptive users

Serotonin and nicotinic acid ribonucleotide metabolic pathways of tryptophan metabolism were studied before and after tryptophan load test in thirty women using oral contraceptive steroids for a period of 2 to 5 years. Ten of them were suffering from depression. Another ten healthy women participated in this study as a control group. Twenty-four-hour urinary excretion of serotonin, 5-hydroxy indole acetic acid and total 5-hydroxyindoles were estimated as indices of serotonin pathway metabolites, while xanthrenate excretion was determined as an index of tryptophan oxygenase pathway. Plasma cortisol, urinary 17-oxosteroids and 17-hydroxycorticosteroids were determined to assess adrenal cortical function. Urinary creatinine output was assayed to check the adequacy of 24-hr urine collection. The changes induced by oral contraceptive steroids on tryptophan and corticosteroid metabolism were correlated with the associated depression. Changes in serotonin metabolism were demonstrated in the depression group before and after tryptophan load test, while in the non-depression group, these changes were only demonstrated after tryptophan load test. Results indicated that alterations in tryptophan metabolism are usually well compensated in the non-depression group but may accentuate or precipitate the development of depression in susceptible women.

Preventive treatment of migraine with mini-doses of danitracene.

SYNOPSISDanitracene is an oral antamine preparation; with three effects: anti‐serotoninic, anti‐histaminic and anti‐depressive. Its lack of unpleasant side effects permits its long use for the preventive treatment of migraine. Its chemical structure‐ring, C‐beta, C‐alpha, amine‐allows specific blockade of receptors for serotonin and histamine geared to the same configuration. Danitracene preventive treatment with 1‐3 x 0.5‐1 mgday for a period of 1‐3‐6 months can almost completely eliminate migraine attacks. Fifty out of 75 patients profited from treatment of 1‐3 x 0.5 mgday showing a drop from 5‐30 attacks per month to 0‐1 attacks per month. During this period 50 cases with high urinary excretion of serotonin, 5‐HIAA or histamine were normalized and relieved of their migraine attacks. Starting with very low doses at night overcomes the sedative anti‐serotonin effect, improves results and avoids dropouts. Two side‐effects typical for anti‐serotonin drugs were observed: sedation or dizziness and hyperorexia. The hypnotic effect tended to disappear after protracted treatment with one 0.5 mg doseday only. The hyperoraexia, however could only be overcome by reduced dosage. Randomization, “double‐blind” and cross‐over design were used in the trial.

Serotonin, 5-hiaa, total estrogen and pregnanediol excretion in urine during therapeutic saline abortion.

In 24 patients, who underwent therapeutic abortion for various reasons between the 17th and 26th week of pregnancy, urinary excretion of serotonin, 5-HIAA, total estrogens, and pregnanediol were measured before, during and after the intra-amniotic injection of hypertonic saline. 20% hypertonic saline solution (160-500 ml) was given by transabdominal injection over a period of 5 min. The four hormones or metabolites were measured during six periods: I; 12-24 hrs, and II: 0-12 hrs before saline administration, III: 0-12 hrs after saline administration, IV: 0-12 hrs during aborion, V: 0-12 hrs and VI: 12-24 hrs after abortion. The results point to the active participation of serotonin in the process of fetal expulsion, as serotonin was increased by over 100% (from 20-22 to 43-47 mu-g/12 hrs) during periods III-IV, and its metabolite 5-HIAA, too, increased by nearly 60% (from 2.4-2.5 to 3.3-3.9 mg/12 hrs). They decreased during the post-abortive periods V-VI. On the other hand, total estrogens decreased only slowly, but continuously, during all 6 periods (4.9, 4.3, 3.4, 3.1, 1.8 and 1.4 mg/12 hrs). Pregnanediol, beginning with 12 mg/12 hrs showed a slight increase during periods III-IV (14.5 and 15.6 mg/12 hrs) and a decrease during periods V-VI (8.0 and 5.8 mg/12 hrs). These findings are interpreted as indicating the disruption of feto-placental function affecting estrogens during periods III-VI. They might demonstrate an accelerated hydrogenation of progesterone into pregnanediol during periods III-IV, followed by a sharp decreased in progesterone/pregnanediol production during periods V-VI.

Imipramine-mediated effects on levodopa metabolism in man

The effect of imipramine (IMP) on levodopa ( l-dopa) metabolism was studied in four normal subjects. IMP pretreatment for 3 consecutive days prior to the administration of 500 mg l-dopa moderately decreased the urinary excretion of dopa. Similarly, IMP pretreatment decreased the urinary excretion of dopamine, norepinephrine and their major acid metabolites. In contrast, IMP pretreatment decreased the urinary excretion of serotonin but increased the excretion of its major acid metabolite, 5-hydroxyindoleacetic acid. The findings suggest that IMP-mediated decreased excretion of dopa and its metabolites studied is partially related to retarded gastrointestinal absorption of l-dopa and that IMP may alter the metabolic pathway of serotonin during l-dopa administration in man.

Urinary excretion of serotonin (5-hydroxytryptamine) and related indoles in normal subjects

A new procedure for determining urinary serotonin in normal subjects was presented. In 23 normals, mean serotonin excretion was 5.28 ± 1.95 μg/h. An improved 5-HIAA test was given. It can be used as a screening method in suspected metastatic carcinoid syndrome patients or for obtaining rapid 5-HIAA results in metabolically normal subjects not taking interfering drugs. A longer and more specific 5-HIAA method was described wherein 5-HIAA and 5-HTP were separated from each other and from serotonin and all three measured independently. Normal subjects failed to show significant increases in urinary serotonin excretion following ingestion of bananas, although their 5-HIAA output levels may approach levels characteristic for metastatic carcinoid patients. 5-HTP determination may be a useful adjunct to urinary serotonin and 5-HIAA in the diagnosis of metastatic carcinoid syndrome, but is subject to severe interference by phenacetin-containing drugs.