OBJECTIVETo develop an analytical method and quality control for determination of zolmitriptan and related substances.

METHODSZolmitriptan and related substances were separated and determined on a shimadzu CLC-C(8) column (150 mm x 6 mm, 10 microm) with a mobile phase of acetonitrile-10 mmol/L phosphate buffer (25:75 pH 7.5) and a flow-rate of 1 ml/min; the UV-VIS detector was operated at 229 nm.

RESULTThe limit of detection for the related substances was 0.5 ng on the zolmitriptan basis (S/N >3). Linear calibration curve was gene rated from 4 - 40 microg/ml with a correlation coefficient of 0.9999. The recovery rate of zolmitriptan was 99.1% with a standard deviation of 0.2%. The results of HPLC method were consistent with those of nonaqueous titration method.

CONCLUSIONHPLC method is a rapid sensitive and accurate method for the determination of zolmitriptan and its related substances.

The erectile dysfunction (ED) and premature ejaculation (PE) are common medical conditions of male sexual dysfunction that affects the sexual lives of millions of men. While many drugs are now available for treating ED and PE, oral pharmacotherapy represents the first-line option for most patients. Phosphodiesterase type-5 (PDE5) inhibitors are currently the most widely prescribed oral agent and have a very satisfactory efficacy-safety profile in all ED patients' categories. Continuous treatments using PDE5 inhibitors and new agents including fast acting PDE5 inhibitors or other intracellular modulators are now under investigation. ED patients who do not respond to oral pharmacotherapy or who cannot use it are good candidates for intracavernosal injection therapy of which efficacy is high but the attrition rate remains significant. Since the pathophysiology of PE is still unclear and there is no approved treatment, it remains to be underdiagnosed and under-treated. The first-line pharmacotherapy for most PE patients is selective serotonin reuptake inhibitors (SSRI) because central 5-hydroxy tryptamine has been implicated as a key mediator of ejaculatory control. Topical anesthetics have also shown varying degrees of efficacy and tolerability. New agents being considered for the on-demand treatment of PE include tramadol and dapoxetine. Therapies for ED or PE will continue to develop as the understanding of those conditions expands. The purpose of this review is to describe the major recent novel advances in the field of medical therapy for the treatment of ED and PE.
Anesthetics ; Benzylamines ; Erectile Dysfunction ; Humans ; Male ; Naphthalenes ; Phosphodiesterase 5 Inhibitors ; Premature Ejaculation ; Serotonin Uptake Inhibitors ; Tramadol ; Tryptamines

Taking medication early on for aborting migraines has proved to be more effective, but trials using triptans during the aura phase have not shown significant effectiveness. Isometheptene compounds are popularly used as an anti-migraine OTC drug. We report a 27-year-old male patient with migraine with aura whose headache attacks were consistently inhibited by an isometheptene compound administered at the early aura phase, while he received no benefits from adequate treatment during the headache phase.
Adult ; Epilepsy* ; Headache ; Humans ; Male ; Migraine Disorders* ; Migraine with Aura ; Tryptamines

Aims: Tryptamine is an amine compound derived from tryptophan by decarboxylation process. This compound can be found in fermented food and beverages, and in human gut and skin as well. This study aims to investigate the effect of tryptamine, on Gram-negative bacteria, namely Escherichia coli, Serratia marcescens and Pseudomonas aeruginosa. Methodology and results: In this study, we used E. coli, S. marcescens and P. aeruginosa due to their relatively observable quorum sensing-regulated phenotype, such as motility, prodigiosin and pyocyanin sequentially. Our results showed that tryptamine started to inhibit the growth and prodigiosin production of S. marcescens at concentration 250 μg/mL, while it inhibits the growth and pyocyanin production of P. aeruginosa at concentration 250 μg/mL and 500 μg/mL, respectively. Tryptamine inhibits both the growth and motility of E. coli at concentration 100 μg/mL. Conclusion, significance and impact of study These results suggest that tryptamine is able to inhibit the growth of E. coli, S. marcescens and P. aeruginosa at relatively high concentration, thus decreases the quorum sensing-regulated phenotypes. It implies that the growth and quorum sensing of Gram-negative bacteria most likely will not be affected by the low concentration of tryptamine that present in the gut.
Tryptamines ; Gram-Negative Bacteria ; Serratia marcescens ; Pseudomonas aeruginosa ; Escherichia coli

Objective This study determined the efficacy of calcitonin gene-related peptide (CGRP) antagonists in the treatment of acute migraine.
Human ; Calcitonin Gene-related Peptide ; Migraine Disorders ; Tryptamines ; Pain

Melatonin has been reported to protect neurons from a variety of neurotoxicity. However, the underlying mechanism by which melatonin exerts its neuroprotective property has not yet been clearly understood. We previously demonstrated that melatonin protected kainic acid-induced neuronal cell death in mouse hippocampus, accompanied by sustained activation of Akt, a critical mediator of neuronal survival. To further elucidate the neuroprotective action of melatonin, we examined in the present study the causal mechanism how Akt signaling pathway is regulated by melatonin in a rat primary astrocyte culture model. Melatonin resulted in increased astrocytic Akt phosphorylation, which was significantly decreased with wortmannin, a specific inhibitor of PI3K, suggesting that activation of Akt by melatonin is mediated through the PI3K-Akt signaling pathway. Furthermore, increased Akt activation was also significantly decreased with luzindole, a non-selective melatonin receptor antagonist. As downstream signaling pathway of Akt activation, increased levels of CREB phoshorylation and GDNF expression were observed, which were also attenuated with wortmannin and luzindole. These results strongly suggest that melatonin exerts its neuroprotective property in astrocytes through the activation of plasma membrane receptors and then PI3K-Akt signaling pathway.
Androstadienes ; Animals ; Astrocytes ; Cell Death ; Cell Membrane ; Glial Cell Line-Derived Neurotrophic Factor ; Hippocampus ; Melatonin ; Mice ; Neurons ; Phosphorylation ; Rats ; Receptors, Melatonin ; Tryptamines

BACKGROUND AND PURPOSE: Frovatriptan is a selective 5-HT1B/1D agonist with a long duration of action and a low incidence of side effects. Although several placebo-controlled trials have documented the clinical efficacy and safety of frovatriptan in adults with migraine, this drug has not previously been studied in Asian including Korean patients. METHODS: In this double-blind multicenter trial, 229 patients with migraine were randomized to receive frovatriptan 2.5 mg or placebo upon the occurrence of a moderate-to-severe migraine. The primary outcome was the 2-hour headache response rate. RESULTS: Frovatriptan significantly increased the 2-hour headache response rate compared with placebo (52.9% vs. 34.0%, p=0.004). The headache response rates at 4, 6, and 12 hours were significantly higher in the frovatriptan group than in the placebo group, as was the pain-free rate at 2 hours (19.0% vs. 5.7%, p=0.004), 4 hours (40.7% vs. 23.0%, p=0.006), and 6 hours (56.1% vs. 34.0%, p=0.002). The median time to a headache response was significantly shorter in the frovatriptan group than in the placebo group (2.00 hours vs. 3.50 hours, p<0.001). The use of rescue medications was more common in the placebo group (p=0.005). Chest tightness associated with triptan was infrequent (2.5%), mild, and transient. CONCLUSIONS: These results demonstrate that 2.5-mg frovatriptan is effective and well tolerated in Korean migraineurs for acute treatment of migraine attacks.
Adult ; Asian Continental Ancestry Group ; Carbazoles ; Headache ; Humans ; Incidence ; Migraine Disorders ; Oxalates ; Thorax ; Tryptamines

Although vestibular migraine is considered to be the most common cause of non-positional recurrent vertigo, well designed clinical trials for the treatment of vestibular migraine are not yet available. Management includes dietary and lifestyle modifications and medications. Since treatment for vestibular migraine generally follows the recommended treatment of migraine, most drugs are also used for the prevention of migraine. In this review, preventive treatment with beta blockers, calcium channel blockers, antiepileptic drugs, antidepressants, acetazolamide and triptans are described. Nonpharmacological management such as diet, sleep and avoidance of triggers are also recommended for vestibular migraine.
Acetazolamide ; Anticonvulsants ; Antidepressive Agents ; Calcium Channel Blockers ; Diet ; Life Style ; Migraine Disorders ; Tryptamines ; Vertigo

Objective To detect the uncontrolled new psychoactive tryptamines involved in drug-related cases with high resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Methods White and brown powder obtained in actual cases were extracted and analyzed by gas chromatography-quadrupole time-of-flight mass spectrometry （GC-QTOF-MS）, ultra-high performance liquid chromatography-linear ion trap quadrupole-orbitrap mass spectrometry （UPLC-LTQ-Orbitrap MS） and ¹H-nuclear magnetic resonance spectroscopy （1H-NMR）. Results After detection by GC-QTOF-MS, the components of white powder showed main characteristic fragment ion peaks at m/z 218.141 0 （molecular ion peak）, 72.080 6 （base peak）, etc. After detection by UPLC-LTQ-Orbitrap MS, its protonated molecular ion was m/z 219.149 4. The main ions in the secondary mass spectrum under the collision-induced dissociation （CID） mode were m/z 160.076 3 and 72.080 8. After detection by GC-QTOF-MS, the components of brown powder showed main characteristic fragment ion peaks at m/z 246.135 7 （molecular ion peak）, 58.065 1 （base peak）, etc. After detection by UPLC-LTQ-Orbitrap MS, its protonated molecular ion was m/z 247.145 0. The main ions in the secondary mass spectrum under CID mode were m/z 202.087 1, 160.076 3 and 134.060 5. NIST 17 library retrieval and ¹H-NMR confirmed that the white powder and brown powder contained new psychoactive tryptamines 4-OH-MET and 4-AcO-DMT, respectively. Conclusion GC-QTOF-MS, UPLC-LTQ-Orbitrap MS and ¹H-NMR can be used together to identify unknown new psychoactive substances.
Chromatography, High Pressure Liquid ; Gas Chromatography-Mass Spectrometry ; Magnetic Resonance Spectroscopy ; Mass Spectrometry ; Tryptamines

Objective To establish a method combining QuEChERS and ultra-high liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） for rapid screening and testing of three types of new psychoactive tryptamines in human blood： 5-MeO-DALT, 5-MeO-MiPT and 5-MeO-DiPT. Methods The effects of the type of extractant, the type and dosage of salting-out agent, and the dosage of adsorbent on the test results of the three tryptamines were investigated. Blood samples were processed by QuEChERS method and then determined by UPLC-MS/MS. Results The linear relationships of 5-MeO-DALT, 5-MeO-MiPT and 5-MeO-DiPT in human blood were good in the range of 0.5-100, 0.5-100 and 0.2-100 ng/mL, respectively, with their coefficients higher than 0.99. The limits of detection （LODs） were 0.1-0.2 ng/mg. The recoveries ranged from 84.86% to 94.57%. Intra-day and inter-day precisions were good. Conclusion The method is simple, rapid, easy to operate and has a high recovery. It is suitable for the qualitative and quantitative study of tryptamines in blood and can provide the reference for public security organs to deal with related cases.
Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Humans ; Limit of Detection ; Tandem Mass Spectrometry ; Tryptamines