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Monoamines, acting as hormones and neurotransmitters, play a critical role in multiple physiological processes ranging from cognitive function and mood to sympathetic nervous system activity, fight-or-flight response and glucose homeostasis. In addition to brain and blood, monoamines are abundant in several tissues, and dysfunction in their synthesis or signaling is associated with various pathological conditions. It was our goal to develop a method to detect these compounds in peripheral murine tissues. In this study, we employed a high-performance liquid chromatography method using electrochemical detection that allows not only detection of catecholamines but also a detailed analysis of nine monoamines and metabolites in murine tissues. Simple tissue extraction procedures were optimized for muscle (gastrocnemius, extensor digitorum longus and soleus), liver, pancreas and white adipose tissue in the range of weight 10-200 mg. The system allowed a limit of detection between 0.625 and 2.5 pg μL-1 for monoamine analytes and their metabolites, including dopamine, 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine, homovanillic acid, norepinephrine, epinephrine, 3-methoxy-4-hydroxyphenylglycol, serotonin and 5-hydroxyindoleacetic acid. Typical concentrations for different monoamines and their metabolization products in these tissues are presented for C57Bl/6 J mice fed a high-fat diet.

Introduction: In the clinical observation of patients suffering from spastic and autonomous dysregulation with hypertonia, intrathecal application of baclofen improved both symptoms. Aim: In this study we investigated the correlation of intrathecal application of baclofen, a specific GABAB ? receptor agonist, and the release of epinephrine, norepinephrine and homovanillin acid from the hypothalamic paraventricular nucleus. The study was part of a collaborative project in which dihydroxyphenylacetic acid (DOPAC), 5 ? hydroxytryptamine (5 ? HT), glutamate and aspartate were quantified while blood pressure was measured. Homovanillic acid (HVA) as a decomposition product of norepinephrine, epinephrine and dopamine was used as a parameter for the release of dopamine. The magnocellular part of the nucleus paraventricularis hypothalami has neuroendocrinological functions and its parvocellular part plays a role in the central control of autonomous functions, e.g. control of blood pressure. Method: We implanted a microdialysis probe in the nucleus paraventricularis hypothalami of 38 Wistar-Rats. In 19 animals 1.5 mg Baclofen was injected in the lateral ventricel and the equivalent quantity of ringer?s solution in the remaining 19 animals as a control group. Norepinephrine, epinephrine and the metabolite HVA were quantified by HPLC. Result: There was no significant difference between the baclofen and control group concerning the release of epinephrine and norepinephrine from the nucleus paraventricularis hypothalami. A significant increase of HVA concentration was observed in the animals treated with baclofen compared to the control group. Outlook: To prove the role of the paraventricularis hypothalamic nucleus in the control of blood pressure and the influence of baclofen on the release of epinephrine, norepinephrine and HVA further studies have to follow.Abstract Introduction: In the clinical observation of patients suffering from spastic and autonomous dysregulation with hypertonia, intrathecal application of baclofen improved both symptoms. Aim: In this study we investigated the correlation of intrathecal application of baclofen, a specific GABAB ? receptor agonist, and the release of epinephrine, norepinephrine and homovanillin acid from the hypothalamic paraventricular nucleus. The study was part of a collaborative project in which dihydroxyphenylacetic acid (DOPAC), 5 ? hydroxytryptamine (5 ? HT), glutamate and aspartate were quantified while blood pressure was measured. Homovanillic acid (HVA) as a decomposition product of norepinephrine, epinephrine and dopamine was used as a parameter for the release of dopamine. The magnocellular part of the nucleus paraventricularis hypothalami has neuroendocrinological functions and its parvocellular part plays a role in the central control of autonomous functions, e.g. control of blood pressure. Method: We implanted a microdialysis probe in the nucleus paraventricularis hypothalami of 38 Wistar-Rats. In 19 animals 1.5 mg Baclofen was injected in the lateral ventricel and the equivalent quantity of ringer?s solution in the remaining 19 animals as a control group. Norepinephrine, epinephrine and the metabolite HVA were quantified by HPLC. Result: There was no significant difference between the baclofen and control group concerning the release of epinephrine and norepinephrine from the nucleus paraventricularis hypothalami. A significant increase of HVA concentration was observed in the animals treated with baclofen compared to the control group. Outlook: To prove the role of the paraventricularis hypothalamic nucleus in the control of blood pressure and the influence of baclofen on the release of epinephrine, norepinephrine and HVA further studies have to follow., Einleitung: In der klinischen Beobachtung an Patienten, die sowohl an einer Spastik, als auch an autonomer Dysregulation unter anderem in Form von entgleister Hypertonie, litten, zeigte sich, dass sich bei intrathekaler Baclofengabe sowohl die Spastik, als auch die Blutdrucksituation besserte. Diese Beobachtung gab Anlass zu einem Gemeinschaftsprojekt, in dem die Neurotransmitter bzw. deren Abbauprodukte Adrenalin, Noradrenalin, HVA, Dopac, 5-HT, Glutamat und Aspartat bestimmt wurden. Parallel wurde intraarteriell der Blutdruck gemessen. Ziel: In dieser Arbeit sollte der Zusammenhang zwischen intrathekaler Baclofenapplikation und Freisetzung von Adrenalin, Noradrenalin und Homovanillinsäure untersucht werden. Homovanillinsäure, als Abbauprodukt von Noradrenalin, Adrenalin und Dopamin wurden als Parameter für die Ausschüttung von Dopamin verwendet. Vom Nucleus paraventricularis hypothalami ist bekannt, dass er sowohl neuroendokrinologische Aufgaben übernimmt, als auch eine Rolle in der zentralen Regulation autonomer Funktion, unter anderen der Kontrolle des Blutdrucks spielt. Die erste Aufgabe wird dem magnozellulären Anteil, die zweite Aufgabe dem parvozellulären Anteil des Nucleus paraventricularis hypothalami zu geschrieben. Baclofen ist ein spezifischer GABA ? B ? Rezeptor Agonist. Methode: Zur Untersuchung implantierten wir eine Mikrodialysesonde in den Nucleus para-ventricularis hypothalami. Von den insgesamt 38 Tieren applizierten 1,5 mg Baclofen 19 Tieren der Verum ? und die entsprechende Menge Ringerlösung 19 Tieren der Kontrollgruppe intrathekal. Mit Hilfe der HPLC bestimmten wir gleichzeitig die für diese Studie relevanten Katecholamine Noradrenalin, Adrenalin und den Metaboliten HVA, als auch die Neurotransmitter bzw. deren Abbauprodukte Dopa, Dopamin, Dopac, 5-HT und 5-HIAA, sowie die Aninosäuren Aspartat und Glutamat im Mikrodialysat. Ergebnis: Es zeigte sich kein signifikanter Unterschied zwischen der Verum- und Kontrollgruppe bezüglich der Ausschüttung von Adrenalin und Noradrenalin aus dem Nucleus paraventricularis hypothalami. Für HVA kann eine signifikante Erhöhung der Werte in der Verum - im Vergleich zur Kontrollgruppe nachgewiesen werden und weisen somit auf eine Beeinflussung durch Baclofen hin. Daher kann nach dieser Studie die Ausgangshypothese lediglich für HVA widerlegt werden, für Adrenalin und Noradrenalin kann sie weder bestätigt noch widerlegt werden. Schlussfolgerung: Um eine Antwort über den Einfluss des Nucleus paraventricularis hypothalami in der zentralen Blutdruckregulation und seine Beeinflussung durch Baclofen auf die Ausschüttung u.a. von Adrenalin, Noradrenalin und HVA zu geben ist sind weitere Studien sicher erforderlich.

The diagnostic value of 123I-mIBG-scintigraphy, bone scintigraphy and catecholamine metabolites in the follow up of neuroblastoma stage IV will be evaluated.Nineteen children suffering from neuroblastoma were analysed retrospectively by 123I-mIBG-scintigraphy, bone scintigraphy and measurement of homovanillic acid, vanillic acid, neuronspecific enclose, lactate dehydrogenase, and ferritine. Follow up was 7-132 (median 36) months.The significance of the methods was dependent on the time of diagnostic use. In principal, 123I-mIBG-scintigraphy has the highest diagnostic impact. For initial staging and diagnosis of recurrence a combination of all three methods can be used. On the contrary, follow up during chemotherapy is best documented by 123I-mIBG-scintigraphy, whereas bone scintigraphy is of limited and measurement of catecholamine metabolites of less diagnostic value.

Cluster headache is a rare, very severe disorder that is clinically well characterized with a relatively poorly understood pathophysiology. Alterations of the hypothalamic-pituitary axis due to chronobiological changes, such as typical temporal pattern of both cluster periods and attacks, point to a central etiopathogenesis. Multiple local and systemic autonomic symptoms are compatible with an altered balance of the sympathetic and parasympathetic nervous system. In this connection, too, a central etiology is postulated. To evaluate the activation of the sympathetic nervous system, in 12 cluster headache patients we investigated the plasma catecholamines norepinephrine and epinephrine four times a day (7.00, 12.00, 17.00, 23.00) in the cluster period. In the cerebrospinal fluid we determined the transmitters norepinephrine, epinephrine, dopamine and the metabolites homovanillic acid (HVA), vanillymandelic acid (VMA) and 5-hydroxyindoleacetic acid (5-HIAA). Values of plasma norepinephrine in the morning (p0.01), in the evening (p0.01) and the daily mean value (223.8 = 58.3 nmol/ml) were significantly decreased in the cluster headache group in comparison to the control group (328.8 = 53.0 nmol/ml, p0.01). The plasma epinephrine showed no significant changes. In the CSF of cluster headache patients norepinephrine (p0.05), HVA (p0.01), and 5-HIAA (p0.01) were significantly decreased. Plasma norepinephrine was correlated with CSF values of HVA and 5-HIAA. The longer the duration of the disease, the lower the values of HVA and 5-HIAA in the CSF of cluster headache patients. Moreover, plasma norepinephrine showed a significant correlation with the duration, the intensity and the frequency of the attacks. The results of this study implicate decreased activity of the sympathetic nervous system with alteration of circadian rhythmicity during the cluster period. The decreased CSF transmitter values may support the hypothesis of a central etiopathogenesis of cluster headache. Moreover, plasma norepinephrine seems to be involved in triggering and continuing the attacks. The anatomical region in which this interface of sympathetic and neurogenic inflammatory processes might be located is the trigemino-vascular system.

The proof for the general evolution of metastatic neuroblastoma from localized disease by a low-speed process is lacking. The epidemiological approach would require the decrease of neuroblastoma related mortality by reduction of the number of metastatic cases per population unit as a result of a screening program. During 1983 through 1990 the neuroblastoma incidence in the FRG was 0.85-1.09 cases per 100,000 children less than 15 years of age. The mortality rate ranged between 0.25 and 0.49 deaths per 100,000 children. The project "Niedersachsen/Nordrhein-Westfalen" started April 1st, 1992 and is investigating urinary catecholamine metabolite excretion in infants at the age of 10-12 months and for a second time in toddlers at 17-19 months. The target population includes 24.7 million inhabitants with 267,000 births per year. The urine sampled on filter paper is analyzed using thin layer chromatography. Positive and questionable positive results are confirmed by HPLC and GC-MS. The aim of the study is to demonstrate the feasibility of the chosen approach. Furthermore first epidemiological data will be obtained. Until a population-based study on neuroblastoma mortality in screened versus controlled populations has proven the usefulness of the screening it cannot be recommended as a general service to the public.

The excretion of the catecholamine-metabolites 3-methoxy-4-hydroxymandelic acid and 3-methoxy-4-hydroxy-phenylacetic acid shows circadian variation. In applying the cosinoranalysis, we tested the normal process of the variation over 3 d and found partly significant circadian rhythms of the excretions with the maxima occurring in the second part of the day to the evening hours and the minima occurring at night. By prescribing the course of the day (fixed time of food intake as well as of sleeping) effects of synchronisation could be found from d 1 to 3. The possible importance of these circadian oscillations for an early or differential diagnosis and the question of the reduction and optimization of the time necessary for collecting urine are discussed.

Tienocarbine (1,9-dimethyl-7,8,9,10-tetrahydrothieno[3,2-e] pyrido[4,3-b] indole lactate) in oral doses of 10 mg X kg-1 lowers dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striata of rats without influencing contents of biogenic amines; this points to a reduced dopamine (DA) turnover. This effect is still present after 28 days of daily application. At the same time the serotonin (5-HT) turnover is not influenced. Tienocarbine displaces 3H-DA and 3H-spiperone from their specific binding sites in the nucleus caudatus of calf brain. Structural variation results in preponderance of either dopamineagonistic (turnover lowered) or antagonistic (turnover increased) properties of the molecules. The whole class of compounds therefore can be considered as mixed dopamine agonists-antagonists.

The synthesis of the title compounds is described. The compounds are characterized by having no cataleptogenic effect and no antagonistic effect against amphetamine stereotypies in experimental animals. The pharmacological results of the rota-rod, spontaneous motility, aggression-test, hexobarbital-potentiation and antagonism to physostigmine are reported.

The circadian rhythm of the excretion of the catecholamines and some main metabolites is investigated in five normal subjects and two patients with a high excretion. In the normal subjects there are remarkable differences in the amplitudes of the variables. At high catecholamine excretions these differences seem to disappear.

A specific and practicable method is described for the quantitative determination of urinary phenol- and indole-carboxylic acids. High specificity is achieved by a preliminary separation of the free acids (extracted from the urine sample) with the aid of organophilic gel chromatography on Sephadex LH 20, followed by gas chromatographic analysis of the silyl derivatives of the acids. The organophilic gel chromatography of the free acids shows a high recovery rate in the micro- and submicrogram range. The difficulties encountered in other techniques in the derivatisation and gas chromatographic separation of the individual components are avoided by using the preliminary separation, and by using N-methyl-N-trimethylsilyl-trifluoroacetamide for the derivatisation. Use of this preparation technique with a direct read-out gas chromatograph with automatic sample introduction, gives high accuracy and precision, and a facility for the determination of a wide range of aromatic acids in urine.

The peripheral administration of oxotremorine caused a significant increase in dihydroxyphenylacetic acid (DOPAC) in the striatum of rats, dopamine (DA) level was unaffected. Injection of oxotremorine into the substantia nigra failed to change the content of dopamine and its acid metabolites homovanillic acid (HVA) and DOPAC in striatum. Injection of oxotremorine or carbachol into the substantia nigra or into the caudate nucleus did not significantly influence the DA-turnover. The partly inconsistent results are discussed in connection with literature data in regard to the existence of excitatory as well as inhibitory cholinergic systems, which are located differently and are involved in the regulation of DA-turnover.

In acute and chronic experiments investigations were made concerning the effect of clozapine, haloperidol, sulpiride and carpipramine on MHPG, HVA and 5-HIAA in rat brain and on motor activity of the animals. The activity of the rats treated with clozapine and haloperidol was reduced on the first day. After 10 days of treatment this effected of clozapine was significantly diminished. The MHPG level increased slightly on the first day of treatment with all four drugs. This elevation was maintained after chronic treatment with carpipramine and sulpiride, whereas clozapine and haloperidol decreased the MHPG content. 5-HIAA values did not show significant changes in acute experiments, whereas in chronic ones there was an increase. Haloperidol and clozapine induced a strong increase of HVA which decreased after 11 days in those animals treated with haloperidol. In comparison to haloperidol, after clozapine application the percentage of HVA-increase was higher in the limbic system than in the nigrostriatum.

The influence of hydrocortisone on the behaviour of the concentration of dopamine (DA), noradrenaline (NA), and homovanillic acid (HVA) were estimated in liver homogenates in the course of the experimental endotoxic shock. The concentration of DA and NA decrease in untreated animals in the 2nd and 4th hour in order to increase significantly in the 6th hour. The concentration of the HVA also increased in the 6th hour after a transitory significant decrease. - The values in the treated animals were in case of DA increased in the 2nd and 4th hour and decreased significantly in the 6th hour. In case of NA they decreased in the 2nd and 4th and increased significantly in the 6th hour and the values for HVA increased significantly in the whole time. The favourable effect of the hydrocortisone in the treated group can be traced back to the increased DA concentration, the decreased NA concentration and the better utilization of the DA by the tissue. This increased HVA could be evidence for them.

A method for the determination of catechol-methyltransferase activity is described, based on the measurement of fluorometric intensity of 7-hydroxy-6-methoxycoumarin (scopoletin), enzymatically produced by dihydroxycoumarin in the presence of the methyl donor S-adenosylmethionine.

The increase in the concentration of homovanillic acid (HVA) in the haloperidol for 6 days compared to a single administration of the drug. The induction of tolerance is probably due to a functional modification of the striatal dopamine (DA)-receptors after repeated administration of the neuroleptic. Atropine given in combination with haloperidol enhances the induction of tolerance. Clozapine (20 mg/kg orally) had no such effect.