Si può desiderare di provare un trattamento naturale disfunzione erettile come un diverso per i problemi di costruzione. Al giorno d oggi ci sono diverse terapie sul mercato, ma un trattamento naturale disfunzione erettile è stato confermato qualche ora e ora di nuovo per dare risultati efficienti e permanenti. Cos è la disfunzione sessuale? L incapacità di sviluppare o sostenere una costruzione abbastanza lungo per fare l amore è chiamato disfunzione erettile, ED https://farmacia-senzaricetta.it/ o (maschio) problemi di erezione. Tutti gli uomini possono avere problemi di costruzione di volta in volta e gli scienziati considerano ED essere presenti se si verificano problemi di costruzione almeno il 25% del tempo. Alcuni fatti duri: ED Può essere dovuto a problemi emotivi. Stress, pressione, giltiness, depressione, bassa autostima e ansia prestazioni può essere la causa dei vostri problemi di costruzione. La ricerca ha confermato che il 90 per cento della disfunzione erettile è fisica in origine, non emotiva. L impotenza colpisce la maggior parte degli uomini durante la loro vita e può essere dovuto a troppo colesterolo, problemi cardiaci, diabete, ipertensione, fumo o alcol. Alcuni rimedi possono essere la ragione. Le questioni legate al movimento sono collegate. Se ti occupi dei tuoi problemi di movimento, hai piu possibilita di risolvere questo problema. Qui ci sono 5 consigli facili su come aumentare la circolazione: 1. Mangia i pasti giusti. Questo ti rendera il flusso sanguigno ovvio. Una grande parte di rimanere sani e anche mantenere il flusso sanguigno ovvio è legato al vostro piano di alimentazione quotidiana e quello che si mangia. Una buona cura per la disfunzione erettile è mangiare un piano a basso contenuto di grassi e grande alimentazione di fibre. Mangiare fibre tutti i giorni e questo viene scoperto in prodotti cerealicoli cereali integrali, frutta e verdura. Evitare il più possibile pasti pronti o pasti non sani. 2. Wonder herbal rimedi. Molti rimedi vegetali per ED eseguire bene come possono migliorare il movimento. Hanno molto meno reazioni avverse rispetto ai farmaci convenzionali e si svolgono in modo efficiente per migliorare hardons e la forza, troppo. Erbe naturali come Ginkgo Biloba sono utilizzati come una strategia per ED. Gli specialisti di erboristeria credono anche che le spezie o le erbe come noce moscata, portano al movimento intorno al corpo, tra cui il pene. 3. Vitamine naturali vitali. Gli scienziati sanitari hanno scoperto che una mancanza di supplemento è tipico tra gli uomini con ED in particolare vitamina A. Se si ha una mancanza del nutriente ossido di zinco, Questo è stato confermato per portare alla disfunzione erettile. Queste inadeguatezze derivano dal fatto che molti valori nutrizionali in quello che mangiamo piano non sono sufficienti. Aggiungere al vostro fabbisogno di nutrienti aumenterà la circolazione del sistema e migliorare questa condizione. Gli integratori alimentari sono completamente naturali, quindi non dovrete preoccuparvi dei rischi di reazioni avverse. Inoltre, queste vitamine naturali sono utili per il vostro benessere over-all. Oltre a questi vantaggi benessere, disfunzione erettile vitamine naturali e integratori costano molto meno di farmaci rimedi. 4. Esercitare. Fai una mossa e non un tablet vibrante. Camminare farà di più per migliorare e sostenere hardons di qualsiasi altra compressa chimica nel lungo periodo. Il fitness fisico manterrà bassi livelli di pressione e mantenere grandi stadi di movimento. Andando per un 20-30 minuti di movimento rapido ogni giorno, può affrontare questo problema e può sostenere la vostra libido senza l uso di qualsiasi farmaco. 5. Sottolineare. Questo è il peggior attaccante per problemi di erezione. Scopri diversi metodi per riposare. Alcuni metodi tipici per riposare includono la lettura di un libro, la meditazione, un bagno rilassante o allenamenti di respirazione. Sto solo imparando alcuni semplici allenamenti di respirazione che possono migliorare significativamente il movimento nel reparto pantaloni. Una naturale disfunzione erettile soluzioni di trattamento stanno diventando sempre più popolare con gli uomini. Questi rimedi a base di erbe sono preferiti perché non hanno reazioni avverse e sono confermati essere efficiente come il farmaco. La maggior parte degli uomini combattere parlano dei loro problemi, in particolare la disfunzione erettile come c è poca discussione sui problemi di erezione. La verita e che ED ha un impatto su piu di dieci milioni di uomini solo negli Stati Uniti. Non siete soli e l aiuto è disponibile.

Microsoft word - asian2004-4_303-306, zhang zp_.doc

Asian Journal of Drug Metabolism and Pharmacokinetics
Copyright by Hong Kong Medical Publisher
ISSN 1608-2281 2004; 4(4): 303-306

Biochemical mechanism of comparison studies of clozapine and
quetiapine by metabonomic method in rats

Zong-Peng Zhang, Ya Su, Nan Yue, Yi-Gui Zhao
Tianjin State Key Laboratory of Pharmacokinetics and Pharmacodynamics, Tianjin Institute of Pharmaceutical Research, Tianjin, 300193, China Abstract
Aim Using metabonomic method to study the biochemical mechanism of antipsycholic agents through
determining the metabolism of dopaminergic neurotransmitters in brain tissues after administration of
clozapine and quetiapine in rats. Methods The determination of serotonin (5-HT), noeradrenaline (NA),
5-hydroxyindoleacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid
(HVA) in diencephalons and striata by HPLC with electrochemical detector following oral administration
of clozapine and quetiapine in rats. Results At doses of clozapine 40 mg·kg-1 and quetiapine 20 and 40
mg·kg-1, they were able to raise the concentrations of DOPAC and HVA in diencephalons and striata.
Conclusion The study result suggested that clozapine and quetiapine stimulated dopamine metabolism. It
could be relative with the antipsychotic pharmacological activity.

Key words
Biochemical mechanism; clozapine; quetiapine; metabonomics；antipsychotics; neurotransmitter Introduction
marketed name by AstraZeneca)，which is a novel dibenzothiazepine antipsychotic developed by Clozapine is the first of a new generation of Zeneca ， is an atypical antipsychotic with many antipsychotic drugs which constitutes a major similarities to clozapine. Both placebo-controlled and advance in the treatment of schizophrenia. Numerous comparative studies in patients with schizophrenia theories have been proposed to explain the have demonstrated that quetiapine has long-term advantages of clozapine over typical neuroleptics. efficacy in both positive and negative domains, as Most of these focus on its effects on dopaminergic well as beneficial effects on affective and cognitive and serotonergic neurotransmission. This article symptoms. Comparative clinical studies confirm that reviews the effects of clozapine and related quetiapine is at least as effective as the standard antipsychotics, chlorpromazine and haloperidol and response rates with quetiapine are similar to those 4, and serotonin (5-HT) 5-HT2A, 5-HT2C, 5-HT3, 5-HT6, and 5-HT7 receptors, as well as its ability to reported with other atypical antipychotics.[3,4] mo d u la te DA and 5 -HT r e lea s e. [ 1] S ev er a l Quetiapine is well tolerated and clinically effective in post-mortem studies have identified increases of the treatment of schizophrenia. The initial hope of 5-HT1A receptor density in frontal cortical areas in investigators was that quetiapine would have schizophrenic patients, and one has found increases antipsychotic potential and that it might share some in the cerebellar vermis. Clozapine has moderate of the properties of clozapine without its toxicity to affinity at the 5-HT1A receptor, and this may be of therapeutic importance.[2] Quetiapine (Seroquel, In this present study, using metabonomic method studied the biochemical mechanism of Correspondence to Prof Zong-Peng Zhang, 308 An-Shan West antipsycholic agents through determining the Road, Research Centre for New Drug Evaluation, Tianjin Institute metabolism of dopaminergic neurotransmitters in of Pharmaceutical Research, Tianjin, 300193, China Tel: +-86 brain tissues after administration of clozapine and quetiapine in rats for comparison of the dopamine 5-HT), and the metabolites, noeradrenaline (NA), 3,4-dihydroxyphenylacetic acid (DOPAC), and Materials and methods
homovanillic acid (HVA) in biosamples by Waters Test animals Wister male rats with body
weight 280-350 g were produced by The animal The condition for determination of 5-HT,
department of Tianjin Institute of Pharmaceutical 5-HIAA, DOPAC and HVA The determination of
Research, Tianjin, China. The rank of experiment 5-HT, 5-HIAA, DOPAC, and HVA in biosamples was establishment was 2 levels. All animals were housed performed by Waters 6000 HPLC with BASLC-4B electrochemical detector. The analytical columns was C18, 5 µm, 150 mm x 4.6 mm I.D. The columns were Test drugs Clozapine was produced by
maintained at 30°C using a temperature controller. Dong-Teng Pharmaceuticas company. Batch Number: The mobile phase consisted of a mixture of 1000 mL 962004. Quetiapine was produced by the Chemical buffer (50 mmol·L-1 sodium citrate, 25 mmol·L-1 Department of Tianjin Institute of Pharmaceutical monobasic sodium phosphate, 10 mmol·L-1 diethylamine hydrochloride, 2.2 mmol·L-1 sodium Reagents Dopamine (DA) ， noeradrenaline
octylsulfonate and 0.03 mmol·L-1 disodium EDTA, (Norepinephrine, NA), dihydroxyphenylacetic acid pH 3.2, adjusted with 85% phosphoric acid), 30 mL (DOPAC)，and homovanillic acid (HVA)，were acetonitrile, 15 mL dimethyl-acetamide, and was filtered through a 0.20 µm filter. The flow rate was Appearance Waters 6000 HPLC with
0.8 mL·min-1. Detection was at a glassy carbon Test method Thirty Wister rats were divided
maintained at a potential of +700 mV vs. Ag/AgCl. into three groups at random (10 eachgroup) and were Using peak high of standard calculates the treated by single oral dose of experimental control concentrations of neurotransmitters and their reagent, clozapine (40mg·kg-1) and seroquel metabolites. (40mg·kg-1) respectively. All rats were decollated one Data Analysis
hour after drug administration, diencephalons and Concentrations of all analytes are expressed as striata were separated out on ice, weighed, and the mean ± SD in the dialysates. For statistical prepared for homogenates at 15000 r·min-1 for 20 analysis, the within group concentration of the seconds after adding 2mL 0.2mmol·L-1 HClO4 cold analytes collected before administration of melatonin solution. The homogenates were then centrifuged at were compared with those collected after 10000 r·min-1 for 10 minutes in high-speed administration using Student’s t-test. For all statistical analyses, a p value of 0.05 or less was considered According to references[6,7] and the established method in our laboratory to determine concentrations of Dopamine(DA), 5-hydroxytryptamine (serotonin, Table 1 Effects of Clozapine and Quetiapine on metabolism of dopamine and noeradrenaline in brain of rats Concentration （μg/g brain tissue）mean±SD 10 1.33±0.37 4.32±0.71 0.93±0.33 1.61±0.39 1.82±0.43** 5.12±1.53 1.61±0.43** 1.52±0.42 2.10±0.51** 5.06±1.26 1.50±0.22** 1.52±0.27 concentrations of DOPAC and HVA in diencephalons and striata. The results were listed in Table 1. It At doses of clozapine 40mg·kg-1 and quetiapine showed that in the two groups, clozapine 40mg·kg-1 20 and 40mg·kg-1, they were able to raise the and quetiapine 40mg·kg-1 the concentrations of DOPAC and HVA were markedly high than these of receptors.[6] Results of this study show that clozapine in control group (P<0.01), and the concentrations of and quetiapine can improve the metabolism of DA in DA and NA were no different between clozapine or diencephalons and striata, and this biochemical quetiapine group and control group. The study result mechanism may be related to their pharmacological suggested that clozapine and quetiapine stimulated According to the data in Table 1, analyzing the demonstrated enormous potential in furthering the effect of the two on drugs metabolic pathway (Fig 1) understanding of, for example, disease processes, suggests that DA is formed middle metabolite toxicological mechanisms, and biomarker discovery. DOPAC (dihyrdoxy phenyl acetic acid) by MAO The biochemical mode-of-action for herbicides and (monoamine oxidase), and last formed HVA by other bioactive compounds can be rapidly and COMT (catechel-O-methyl transferase). The similar simultaneously classified by automated pattern effect of two drugs on DA metabolic pathway is recognition of the metabonome. Metabonomics can considered that they possess increasing dopaminergic be applied at any stage in drug discovery and development processes, when used in one or more of the following settings: predictive biomarkers for drug-related effects in animal models; understanding DA ────→ DOPAC───→ HVA
of the biochemical mechanisms of action to target-organ or to target-organ pathologies in animal to man; developing biomarkers for toxicities in non-clinical development; and predictive biomarkers Discussion
for drug-related effects in man during Phase II and Phase III clinical trails.[9-13 Metabonomics can be In the central nervous system, dopaminergic directly understood as the physiological and neurotransmission is mediated through two main biochemical situation by its “metabonome profile” as types of postsynaptic receptors termed D1 and D2. a whole. In this pare, we applied metabonomic The D1 receptor is linked to stimulation of adenylate method to discover the biochemical mechanism of cyclase; D2 receptor either inhibit adenylate cyclase antipsycholic agents through determining the change or are linked to phospholipase C, postassium channels or calcium mobilization. The clinical potency of antipsychotic agents correlateds best with the affinity for D2 receptor. Compared with other References
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