The distribution of the metabolites of noradrenaline, 1‐(3,4‐dihydroxyphenyl)ethane‐1,2‐diol (DOPEG) and 1‐(4‐hydroxy‐3‐methoxyphenyl)ethane‐1,2‐diol (MOPEG), in the brain of the mouse has been investigated. The rate of disappearance of the metabolites after inhibition of the enzyme monoamine oxidase has been used to estimate their turnover rates in the mouse hypothalamus. It was concluded that the turnover of DOPEG was much faster than that of MOPEG. When mice were treated with reserpine dissolved in 5% ascorbic acid solution there was an increase in the hypothalamic concentration of both MOPEG and DOPEG. However, similar increases in the concentrations of the two metabolites were seen when the animals were treated with 5% ascorbic acid solution alone. The administration of tropolone, an inhibitor of the enzyme catechol‐ O ‐methyl transferase, resulted in an increase in the concentration of DOPEG. Mice, exposed to a temperature of −15° C showed increased hypothalamic concentrations of both DOPEG and MOPEG. The rates of formation in the mouse striatum of 3,4‐dihydroxyphenylacetic acid (DOPAC) and 4‐hydroxy‐3‐methoxyphenylacetic acid (HVA), acidic metabolites of dopamine, were compared with the turnover rate of dopamine, estimated from the rate at which this catecholamine disappears after treatment with α‐methyl‐ p ‐tyrosine. It was concluded that the estimate of dopamine turnover obtained by this method is likely to be too large because of the compensatory feedback mechanism which is thought to play a role in the metabolism of dopamine in the brain.

Abstract.Six parkinsonian patients have been treated with increasing oral doses ofL‐3,4‐dihydroxyphenylalanine (L‐dopa) up to 8.25 g/d. Previous anticholinergic therapy had been discontinued. Four of the patients were remarkably improved; the best effect was observed on the akinesia. TheL‐dopa treatment was discontinued in two of the patients as they were not markedly improved but displayed considerable side‐effects. Nausea and occasionally vomiting were observed in most patients. Hyperkinesia occurred at the high dose levels. Their mood was elevated but mental disturbance developed in four of the patients. In two of these patients the disturbance disappeared after reduction of the dose. Most of theL‐dopa was metabolized to dopamine outside the brain. Large diurnal variations of the dopa level in blood were observed in agreement with similar variations in the therapeutic effect.

Publisher Summary The active transfer of acid monoamine metabolites from the brain tissue operates with varying effectiveness in different animal species. Rats, with a rather low basal value of the acid dopamine metabolite, homovanillic acid (HVA), in the caudate nucleus (about 0.2 μg/gm), seem to have a very active transfer mechanism for both HVA and 5-HIAA. Rabbits, on the other hand, have a much higher normal value of HVA in the caudate nucleus (about 3.0 μg/gm), whereas the levels of the brainstem 5-HIAA are essentially the same (0.7-1.0 μg/gm) in the two species. This chapter presents some findings, which imply a reduced turnover rate of 5-HT in the brain after lysergic acid diethylamide (LSD). LSD causes a reduced rate of 5-HT depletion in the rat brain after pretreatment with a-propyl-3.4-dopacetarnide (H 22/54), an inhibitor of monoamino biosynthesis. This indicates a reduced turnover rate of 5-HT. The dopamine depletion rate is unaffected.

Journal Article Effect of probenecid on the level of homovanillic acid in the corpus striatum Get access B Werdinius B Werdinius Department of Pharmacology, University of Göteborg, Sweden Search for other works by this author on: Oxford Academic Google Scholar Journal of Pharmacy and Pharmacology, Volume 18, Issue 8, August 1966, Pages 546–547, https://doi.org/10.1111/j.2042-7158.1966.tb07926.x Published: 12 April 2011 Article history Received: 31 May 1966 Published: 12 April 2011

Journal of NeurochemistryVolume 13, Issue 12 p. 1545-1548 ACID MONOAMINE METABOLITES OF CEREBROSPINAL FLUID IN MENTAL DEPRESSION AND MANIA S. J. Dencker, S. J. Dencker Lillhagen Mental Hospital and Department of Pharmacology, University of Göteborg, SwedenSearch for more papers by this authorU. Malm, U. Malm Lillhagen Mental Hospital and Department of Pharmacology, University of Göteborg, SwedenSearch for more papers by this authorB.-E. Roos, B.-E. Roos Lillhagen Mental Hospital and Department of Pharmacology, University of Göteborg, SwedenSearch for more papers by this authorB. Werdinius, B. Werdinius Lillhagen Mental Hospital and Department of Pharmacology, University of Göteborg, SwedenSearch for more papers by this author S. J. Dencker, S. J. Dencker Lillhagen Mental Hospital and Department of Pharmacology, University of Göteborg, SwedenSearch for more papers by this authorU. Malm, U. Malm Lillhagen Mental Hospital and Department of Pharmacology, University of Göteborg, SwedenSearch for more papers by this authorB.-E. Roos, B.-E. Roos Lillhagen Mental Hospital and Department of Pharmacology, University of Göteborg, SwedenSearch for more papers by this authorB. Werdinius, B. Werdinius Lillhagen Mental Hospital and Department of Pharmacology, University of Göteborg, SwedenSearch for more papers by this author First published: December 1966 https://doi.org/10.1111/j.1471-4159.1966.tb04320.xCitations: 179Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume13, Issue12December 1966Pages 1545-1548 RelatedInformation

Accumulating evidence suggests that antipsychotics affect dopamine release from dopaminergic neurons, but the precise mechanisms are not fully understood. Besides, there are few studies on the effects of antipsychotics on intracellular dopamine content. In this study, the effects of 8 antipsychotics on dopamine release and intracellular dopamine content in PC12 cells were investigated. Pretreatment with haloperidol, spiperone, pimozide, aripiprazole and risperidone markedly inhibited high potassium-evoked dopamine release. By contrast, pretreatment with chlorpromazine slightly increased high potassium-evoked dopamine release, while pretreatment with sulpiride and olanzapine had no effect. Haloperidol, spiperone, pimozide, chlorpromazine, aripiprazole and olanzapine evoked dopamine release, while sulpiride and risperidone had no effect. In addition, haloperidol, spiperone, pimozide, aripiprazole and risperidone reduced intracellular dopamine content in a concentration-dependent manner. These results suggest that the reduction in high potassium-evoked dopamine release by pretreatment with antipsychotics results from the reduction in vesicular dopamine content. Treatment with the 8 antipsychotics did not affect the expression of total or phosphorylated tyrosine hydroxylase. Instead, haloperidol, spiperone, pimozide and aripiprazole as well as reserpine transiently increased extracellular levels of dopamine metabolites. In addition, haloperidol, spiperone, pimozide, aripiprazole and risperidone reduced vesicular [3H]dopamine transport. These results suggest that the inhibition of vesicular dopamine transport by haloperidol, spiperone, pimozide and aripiprazole results in a reduction in vesicular dopamine content.

Methods for determination of the acid metabolites of 5-hydroxytryptamine (5-hydroxyindole acetic acid) and dopamine (3,4-dihydroxyphenyl acetic acid and homovanillic acid) have been developed. Simultaneous determinations of the acids and the amines in brain have shown that the concentrations of the amines are reduced after both α-methyl DOPA and reserpine while those of the acids are reduced after a-methyl DOPA and increased after reserpine. The main effect of a-methyl DOPA on the 5-hydroxytryptamine metabolism seems to be an inhibition of the step tryptophan to 5-hydroxytryptophan while most of the actions of reserpine may be explained by a release of the monoamines from the store.

Es wird papierchromatographisch gezeigt, dass Cerebrospinalflüssigkeit gesunder Menschen sowohl Homovanillinsäure als auch 3-Methoxy-4-hydroxymandelsäure enthält. Die Konzentration der ersteren ist etwa 75 ng/ml und die der letzteren etwa 25 ng/ml.

Acta Pharmacologica et ToxicologicaVolume 19, Issue 1 p. 43-46 Effect of Temperature on the Action of Reserpine Bengt Werdinius, Bengt Werdinius From the Department of Pharmacology, University of Göteborg, Göteborg, Sweden.Search for more papers by this author Bengt Werdinius, Bengt Werdinius From the Department of Pharmacology, University of Göteborg, Göteborg, Sweden.Search for more papers by this author First published: May 1962 https://doi.org/10.1111/j.1600-0773.1962.tb00337.xCitations: 14AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume19, Issue1May 1962Pages 43-46 RelatedInformation