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5 htp

Jacob P R Jacobsen, Andrew D Krystal, K Ranga R Krishnan, Marc G Caron
Serotonin transporter (SERT) inhibitors treat depression by elevating brain extracellular 5-hydroxytryptamine (5-HTExt). However, only one-third of patients respond adequately. Treatment-resistant depression (TRD) is a major unmet need. Interestingly, elevating 5-HTExt beyond what is achieved by a SERT inhibitor appears to treat TRD. Adjunctive administration of 5-hydroxytryptophan (5-HTP) safely elevates 5-HTExt beyond the SERT inhibitor effect in humans; however, 5-HTP cannot be a clinically viable drug because of its poor pharmacokinetics...
September 28, 2016: Trends in Pharmacological Sciences
Olle Eriksson, Anders Wall, Ulf Olsson, Ina Marteinsdottir, Maria Holstad, Hans Ågren, Per Hartvig, Bengt Långström, Tord Naessén
STUDY OBJECTIVE: To investigate potential quantitative and qualitative differences in brain serotonergic activity between women with Premenstrual Dysphoria (PMD) and asymptomatic controls. BACKGROUND: Serotonin-augmenting drugs alleviate premenstrual mood symptoms in the majority of women with PMD while serotonin-depleting diets worsen PMD symptoms, both indicating intrinsic differences in brain serotonergic activity in women with PMD compared to asymptomatic women...
2016: PloS One
Noble Kumar Talari, Manas Panigrahi, Sailaja Madigubba, Sundaram Challa, Prakash Babu Phanithi
Meningiomas are the neoplasms that arise from the arachnoid cells of the meninges. It was reported that cancer cells escape from immune system through the metabolism of an aromatic essential amino acid tryptophan (TRP) via Kynurenine (KYN) pathway. However, the role of TRP metabolites such as, 5-Hydroxy tryptophan (5-HTP), 5-Hydroxy tryptamine (5-HT), N-acetyl serotonin (NAS), Melatonin (MEL), KYN, N-acetyl tryptamine, 5-Hydroxy indole acetic acid (5-HIAA) and 5-Methoxy indole acetic acid is not yet evaluated in human meningioma...
July 29, 2016: Journal of Neuro-oncology
Samantha R Weaver, Austin P Prichard, Elizabeth L Endres, Stefanie A Newhouse, Tonia L Peters, Peter M Crump, Matthew S Akins, Thomas D Crenshaw, Rupert M Bruckmaier, Laura L Hernandez
Hypocalcemia is a metabolic disorder that affects dairy cows during the transition from pregnancy to lactation. Twelve multiparous Holstein cows and twelve multiparous Jersey cows were intravenously infused daily for approximately 7 days prepartum with either saline or 1.0mg/kg bodyweight of the immediate precursor to serotonin synthesis, 5hydroxy-l-tryptophan (5-HTP). On infusion days, blood was collected before, after, and at 2, 4, and 8h postinfusion. Blood and urine were collected daily before the infusion period, for 14 days postpartum and on day 30 postpartum...
July 2016: Journal of Endocrinology
Suneeta Yadav, Chandra Mohini Chaturvedi
Avian literature reports the modulation of 'photoperiodic gonadal responses' by the temporal phase relation of serotonergic and dopaminergic oscillations in Japanese quail. But, the modulation of 'light colour responses' by the temporal synergism of neural oscillations is not yet known. Hence the present study was designed to investigate the interaction of the light colour (blue, red) and the phase relation of neural oscillations in the reproductive regulation of Japanese quail. Three week old male Japanese quail were divided into two groups and maintained under a long day length condition (16L:8D) and were exposed to a 30 lux intensity of blue LED (light emitting diode) (B LED) and a red LED light (R LED)...
September 2016: Journal of Photochemistry and Photobiology. B, Biology
Olof Eriksson, Ramkumar Selvaraju, Torsten Eich, Mariam Willny, Torkel B Brismar, Lina Carlbom, Håkan Ahlström, Gunnar Tufvesson, Torbjörn Lundgren, Olle Korsgren
No imaging methodology currently exists to monitor viable islet mass after clinical intraportal islet transplantation. We investigated the potential of the endocrine positron emission tomography (PET) marker [(11)C]5-hydroxytryptophan ([(11)C]5-HTP) for this purpose. In a preclinical proof-of-concept study, the ex vivo and in vivo [(11)C]5-HTP signal was compared with the number of islets transplanted in rats. In a clinical study, human subjects with an intraportal islet graft (n = 8) underwent two [(11)C]5-HTP PET and MRI examinations 8 months apart...
September 2016: Diabetes
Honghai Zhang, Haiting Zhao, Xiaoxuan Yang, Qingsheng Xue, Joseph F Cotten, Hua-Jun Feng
OBJECTIVE: The DBA/1 mouse is a relevant animal model of sudden unexpected death in epilepsy (SUDEP), as it exhibits seizure-induced respiratory arrest (S-IRA) evoked by acoustic stimulation, followed by cardiac arrhythmia and death. Defects in serotonergic neurotransmission may contribute to S-IRA. The tryptophan hydroxylase-2 (TPH2) enzyme converts L-tryptophan to 5-hydroxytryptophan (5-HTP), a precursor for central nervous system (CNS) serotonin (5-HT) synthesis; and DBA/1 mice have a polymorphism that decreases TPH2 activity...
August 2016: Epilepsia
Somanshu Banerjee, Kazuyoshi Tsutsui, Chandra Mohini Chaturvedi
Reproductive performance of many avian species, including Japanese quail, is reported to be modulated by specific temporal phase relation of serotonergic and dopaminergic oscillations. Accordingly, it has been shown that the serotonin precursor 5-HTP and the dopamine precursor l-DOPA given 8 h apart induce gonadal suppression and given 12 h apart lead to gonadal stimulation, while other temporal relationships were found to be ineffective. In the present study, we investigated the effects of 8- and 12-h phase relation of neural oscillations on testicular responses including expression of GnRH-I, GnIH, pro-apoptotic proteins (p53 and Bax), inactive and active executioner caspase-3, and the uncleaved DNA repair enzyme PARP-1...
May 15, 2016: Journal of Experimental Biology
Tomas Furmark, Ina Marteinsdottir, Andreas Frick, Kerstin Heurling, Maria Tillfors, Lieuwe Appel, Gunnar Antoni, Per Hartvig, Håkan Fischer, Bengt Långström, Elias Eriksson, Mats Fredrikson
It is disputed whether anxiety disorders, like social anxiety disorder, are characterized by serotonin over- or underactivity. Here, we evaluated whether our recent finding of elevated neural serotonin synthesis rate in patients with social anxiety disorder could be reproduced in a separate cohort, and whether allelic variation in the tryptophan hydroxylase-2 (TPH2) G-703T polymorphism relates to differences in serotonin synthesis assessed with positron emission tomography. Eighteen social anxiety disorder patients and six healthy controls were scanned during 60 minutes in a resting state using positron emission tomography and 5-hydroxy-L-[β -(11)C]tryptophan, [(11)C]5-HTP, a substrate of the second enzymatic step in serotonin synthesis...
October 2016: Journal of Psychopharmacology
Mark Flint, John T Than
The enhanced ability to direct sexual reproduction may lead to improved restoration outcomes for Acropora cervicornis. Gravid fragments of A. cervicornis were maintained in a laboratory for two sequential trials in the seven days prior to natural spawning in the Florida Keys. Ten replicates of five chemicals known to affect spawning in various invertebrate taxa were tested. Hydrogen peroxide at 2 mM (70%) and L-5-hydroxytryptophan (5-HTP) at 5 (40%) and 20 µM (30%) induced spawning within 15.4 h, 38.8 h and 26...
2016: PeerJ
Ki-Bae Hong, Yooheon Park, Hyung Joo Suh
The aim of this study was to investigate the sleep-promoting effect of combined γ-aminobutyric acid (GABA) and 5-hydroxytryptophan (5-HTP) on sleep quality and quantity in vertebrate models. Pentobarbital-induced sleep test and electroencephalogram (EEG) analysis were applied to investigate sleep latency, duration, total sleeping time and sleep quality of two amino acids and GABA/5-HTP mixture. In addition, real-time PCR and HPLC analysis were applied to analyze the signaling pathway. The GABA/5-HTP mixture significantly regulated the sleep latency, duration (p<0...
September 1, 2016: Behavioural Brain Research
Elżbieta Szacoń, Marzena Rządkowska, Agnieszka A Kaczor, Ewa Kędzierska, Jolanta Orzelska-Górka, Sylwia Fidecka, Dariusz Matosiuk
Novel 1-(1,4-alkylaryldisubstituted-4,5-dihydro-1H-imidazo)-3-substituted urea derivatives have been synthesized and evaluated for their central nervous system activity. Compounds 3a-m were prepared in the reaction between the respective 1-alkyl-4-aryl-4,5-dihydro-1H-imidazol-2-amines 1a-c and appropriate isocyanates 2 in dichloromethane. The compounds were subjected to in silico ADMET studies in order to select best candidates for in vivo experiments. The effects of the compounds on the spontaneous locomotor activity and amphetamine-evoked hyperactivity were estimated...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Kimio Sugaya, Saori Nishijima, Katsumi Kadekawa, Katsuhiro Ashitomi, Tomoyuki Ueda, Hideyuki Yamamoto, Tsuyoshi Hattori
AIMS: We examined the mechanism of action of naftopidil, an α1D/A blocker, on spinal descending serotonergic neurotransmission for the micturition reflex. METHODS: We examined (1) urinary 5-hydroxyindole acetic acid (5-HIAA) after intraperitoneal administration of saline, para-chlorophenylalanine (PCPA; a serotonin synthetic enzyme inhibitor), and/or 5-hydroxytryptophan (5-HTP; a serotonin precursor); (2) isovolumetric cystometry after intraperitoneal administration of saline, PCPA, and/or 5-HTP and intravenous injection of naftopidil; and (3) isovolumetric cystometry before and after intrathecal administration of serotonin (5-HT) receptor antagonists and intravenous injection of naftopidil...
April 29, 2016: Neurourology and Urodynamics
Anna Bielenica, Ewa Kędzierska, Michał Koliński, Sebastian Kmiecik, Andrzej Koliński, Ferdinando Fiorino, Beatrice Severino, Elisa Magli, Angela Corvino, Ilaria Rossi, Paola Massarelli, Anna E Kozioł, Aleksandra Sawczenko, Marta Struga
A series of 10 thiourea derivatives have been synthesized by the reaction of aromatic amine with a substituted aryl (compounds 1-3, 6-8) and alkylphenyl (4, 5, 9, 10) isothiocyanates. Their in vitro and in vivo pharmacological properties were studied. Among the evaluated compounds, two displayed very high affinity for the 5-HT2A receptor (1-0.043 nM and 5-0.6 nM), being selective over the 5-HT2C receptor. Derivatives 3, 5, 9, 10 by 70-89% diminished L-5-HTP-induced head twitch episodes. Compounds 1 and 5 as the 5-HT2A receptor antagonists produced a dose-dependent decrease in the number of DOI-elicited HTR...
June 30, 2016: European Journal of Medicinal Chemistry
Edmond Balidemaj, Henny Petra Kok, Gerben Schooneveldt, Astrid L H M W van Lier, Rob F Remis, Lukas J A Stalpers, Henrike Westerveld, Aart J Nederveen, Cornelis A T van den Berg, Johannes Crezee
Introduction The reliability of hyperthermia treatment planning (HTP) is strongly dependent on the accuracy of the electric properties of each tissue. The values currently used are mostly based on ex vivo measurements. In this study, in vivo conductivity of human muscle, bladder content and cervical tumours, acquired with magnetic resonance-based electric properties tomography (MR-EPT), are exploited to investigate the effect on HTP for cervical cancer patients. Methods Temperature-based optimisation of five different patients was performed using literature-based conductivity values yielding certain antenna settings, which are then used to compute the temperature distribution of the patient models with EPT-based conductivity values...
August 2016: International Journal of Hyperthermia
Chakri Gavva, Ravindra Sarode, Deepak Agrawal, James Burner
OBJECTIVES: Acute hypertriglyceridemia induced pancreatitis (HTP) presents with a more severe clinical course compared to other etiologies of pancreatitis. Therapeutic plasma exchange (TPE) is a potential treatment option for lowering plasma triglycerides and possibly decreasing morbidity and mortality. However, clinical data regarding its effectiveness are limited. METHODS: We retrospectively examined the clinical data and outcomes of 13 consecutive episodes of HTP in which TPE was employed to reduce plasma triglycerides during a 15-month period...
February 2016: Transfusion and Apheresis Science
Jacob Pr Jacobsen, Meghan L Rudder, Wendy Roberts, Elizabeth L Royer, Taylor J Robinson, Adrianna Oh, Ivan Spasojevic, Benjamin D Sachs, Marc G Caron
Drugs, notably SSRIs, that elevate brain extracellular 5-HT (5-HTExt) are antidepressants. Unfortunately, most patients fail to remit. Multipronged clinical evidence suggests that elevating 5-HTExt beyond the SSRI effect enhances antidepressant efficacy, but previous such drug strategies had prohibitive limitations. In humans, adjunct treatment with the 5-HT precursor 5-hydroxytryptophan (5-HTP) elevates 5-HTExt beyond the SSRI effect. Small pilot trials suggest that adjunct 5-HTP can confer antidepressant response in treatment-resistant depression (TRD)...
August 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Ki-Bae Hong, Yooheon Park, Hyung Joo Suh
AIMS: This study was to investigate the sleep promoting effects of combined γ-aminobutyric acid (GABA) and 5-hydroxytryptophan (5-HTP), by examining neuronal processes governing mRNA level alterations, as well as assessing neuromodulator concentrations, in a fruit fly model. MAIN METHODS: Behavioral assays were applied to investigate subjective nighttime activity, sleep episodes, and total duration of subjective nighttime sleep of two amino acids and GABA/5-HTP mixture with caffeine treated flies...
April 1, 2016: Life Sciences
Sophie J van Asselt, Adrienne H Brouwers, Hendrik M van Dullemen, Eric J van der Jagt, Alfons H Bongaerts, Klaas P Koopmans, Ido P Kema, Bernard A Zonnenberg, Henri J Timmers, Wouter W de Herder, Wim J Sluiter, Elisabeth G de Vries, Thera P Links
BACKGROUND: Patients with von Hippel-Lindau (VHL) disease are prone to develop pancreatic neuroendocrine tumors (pNETs). However, the best imaging technique for early detection of pNETs in VHL is currently unknown. In a head-to-head comparison, we evaluated endoscopic ultrasound (EUS) and (11)C-5-hydroxytryptophan positron emission tomography ((11)C-5-HTP PET) compared with conventional screening techniques for early detection of pancreatic solid lesions in VHL patients. METHODS: We conducted a cross-sectional, prospective study in 22 patients at a tertiary care university medical center...
May 2016: European Journal of Endocrinology
Kara Kaplan, Ashley E Echert, Ben Massat, Madeleine M Puissant, Oleg Palygin, Aron M Geurts, Matthew R Hodges
Genetic deletion of brain serotonin (5-HT) neurons in mice leads to ventilatory deficits and increased neonatal mortality during development. However, it is unclear if the loss of the 5-HT neurons or the loss of the neurochemical 5-HT led to the observed physiologic deficits. Herein, we generated a mutant rat model with constitutive central nervous system (CNS) 5-HT depletion by mutation of the tryptophan hydroxylase 2 (Tph2) gene in dark agouti (DA(Tph2-/-)) rats. DA(Tph2-/-) rats lacked TPH immunoreactivity and brain 5-HT but retain dopa decarboxylase-expressing raphe neurons...
May 1, 2016: Journal of Applied Physiology
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