Dopamine metabolites

MAO converts dopamine to DOPAC (3,4-dihydrox-yphenylacetic acid), which can be further metabolized by COMT to form homovanillic acid (HVA). HVA is the main product of dopamine metabolism and the principal dopamine metabolite in urine. Increased neuronal dopaminergic activity is associated with increases in plasma concentrations of DOPAC and HVA. COMT preferentially methylates dopamine at the 3 -hydroxyl position and utilizes S-adenosyl-L-methio-nine as a methyl group donor. COMT is expressed widely in the periphery and in glial cells. In PD, COMT has been targeted since it can convert l-DOPA to inactive 3-OMD (3-O-methyl-dopa). In the presence of an AADC inhibitor such as carbidopa, 3-OMD is the major metabolite of l-DOPA treatment. 

Insight into the state of dopaminergic tone is best obtained from measurements of extracellular dopamine in microdialysate samples collected from the behaving organism. Striatal (Paulson and Robinson 1994 Smith et al. 1992 Castaneda et al. 2004) and prefrontal cortical (Feenstra et al. 2000) dopamine levels rise in anticipation of, and are maintained throughout, the major wakefulness period in the rat, in concert with declines in dopamine metabolites (i.e., DOPAC, HVA, and 5-HIAA) (Smith et al. 1992 Whittaker et al. 1997). This pattern is... 

Altered dopaminergic system function has been implicated in major depression. Patients with major depression have been reported to have lower CSF levels of the dopamine metabolite homovanillic acid (HVA) compared to nondepressed controls, with more severely depressed patients having still lower CSF HVA levels (see [42] for a... 

The effects of developmental exposure of pyrethroids on the dopaminergic system, which is considered to be related to behavior, were examined in several studies, but inconsistent results were obtained. Administration of deltamethrin between gestation day 6 and 15 induced increase of DOPAC (dopamine metabolite) levels in adult rats [54]. Exposure of fenvalerate on gestation day 18 and during postnatal days 2-5 produced no effect on monoamine levels on postnatal day 21 [55]. Gestational and lactational exposure to fenvalerate decreased and increased 3H-spiroperidol binding in striatum after development, respectively, whereas only lactational exposure of cypermethrin induced increase in 3H-spiroperidol binding [56]. 

D. R. Cooper, C. Marrel, H. van de Waterbeemd, B. Testa, P. Jenner, C. D. Marsden, l-Dopa Esters as Potential Prodrugs Behavioural Activity in Experimental Models of Parkinson s Disease , J. Pharm. Pharmacol. 1987, 39, 627 - 635 D. R. Cooper, C. Marrel, H. van de Waterbeemd, B. Testa, P. Jenner, C. D. Marsden, L-Dopa Esters as Potential Prodrugs Effect on Brain Concentration of Dopamine Metabolites in Reserpi-nized Mice , J. Pharm. Pharmacol. 1987, 39, 809-818. 

The antischizophrenic actions of these drugs may not consist simply of postsynaptic blockade of hyperactive dopamine systems. Such a blockade occurs within hours, while most symptoms improve over weeks. This discrepancy in the latency to therapeutic effect has been hypothesized to be linked to drug-induced changes in dopaminergic activity after initiation of therapy, dopamine turnover increases, but after continued antipsychotic treatment, tolerance develops and dopamine metabolism returns to normal. This downward adjustment of dopaminergic activity is consistent with the decreased plasma concentrations of the dopamine metabolite homovanillic acid, an observation that correlates temporally with the clinical response to drug treatment. 

Nicotine, 4 phenylpyridine, and hydrazine, administered to mice, prevented the decrease in dopamine metabolite levels induced by MPTP, but there was no significant effect on dopamine levels. The compounds did not inhibit monoamine oxidase (MAO) activity in cerebral tissue in vivo. In vitro, an extract produced significant inhibition of MAO A and B activities in the... 

Low cerebrospinal fluid (CSF) concentrations of homovanillic acid, a dopamine metabolite, were associated with suicide attempts in two pediatric studies (Kruesi et al., 1992 L. Greenhill, personal communication). 

Low serotonin and dopamine metabolite concentrations in cerebrospinal fluid from bulimic patients with frequent binge episodes. Arch Gen Psychiatry 49 132-138. 

If schizophrenia results from an elevated dopamine content of the brain, the fault may lie with either an oversupply or a reduced rate of metabolism of dopamine. The possibilities of reduced activity of monoamine oxidase or of dopamine (i-hydroxylase have both been suggested. The plasma level of the dopamine metabolite homovanillic acid (Fig. 30-26) is elevated in schizophrenia and is correlated with the... 

Electrochemical binding assays have also been applied for testing computational predictions which render the highest stabilization energy for the pre-polymerization mixture of several formulations traditionally used in non-covalent MIPs [119]. The batch binding assays and voltammetric detection confirm the theoretically best monomer-porogen solvent mixture for preparation of a recognition material for the dopamine metabolite homovanillic acid. 

Sukul NC. 1990. Increase in serotonin and dopamine metabolites in mouse hypothalamus following oral administration of Agaricus muscarius 12, a homoeopathic drug. Sci cult 56 134-137. 

It has not been possible to show abnormalities in overall dopamine content of brains of people with schizophrenia. Total dopamine content can, incidentally, only be measured at post-mortem (Scott 2006), and overall such studies have not shown any differences between people with schizophrenia and those without (Reynolds Czudek 1988). As one of the main researchers in the field put it, the dopamine content is found to be normal in the schizophrenic brain (Seeman 1995). Research into levels of dopamine metabolites in the cerebrospinal fluid,3 which initially claimed to find increased levels in people with schizophrenia, also proved to be inconclusive when people who had not been treated with drugs were investigated (Reynolds 1989 Tuckwell Koziol 1993). 

Rauste-von Wright, M. Frankenhaeuser, M. 1989, Females emotionality as reflected in the excretion of the dopamine metabolite HVA during mental stress, Psychol.Rep., vol. 64, no. 3, Pt 1, pp. 856-858. 

Widerlov E, Kilts CD, Mailman RB, Nemeroff CB, McCown TJ, Prange AJ, Breese GR (1982) Increase in dopamine metabolites in rat brain by neurotensin. J Pharmacol Exp Ther 222 1-6. 

Wilk, S., Stanley, M. (1978). Dopamine metabolites in human brain. Psychopharmacology (Berl.) 57 77-81. 

In anodic oxidation studies on neurotransmitters, generation of 6 rt/70-quinone (XXIX) occurred during controlled potential oxidation of tetrahydropapaveroline (XXVIII), a dopamine metabolite [Eq. (10)] [34]. In the absence of strong nucleophiles, XXIX underwent intramolecular Michael addition to give a transient intermediate, which oxidized at a lower potential than XXVIII. 

Studies have found a positive correlation between levels of HVA (a dopamine metabolite) in plasma and clinical severity. Also, many studies have found an increase in the number of D2 receptors in the striatum and nucleus acumbens from schizophrenics (Bachus et al. 1996). 

Analysis of salsoline and/or salsolidine has been studied by t.l.c. and fluorometry, spectrophotometry, and photometric titration. A new ion-exchange method has been developed for isolating these alkaloids from Salsola richleri Salsolinol has been identified as a major dopamine metabolite in ripening bananas, using cyclic voltammetry, t.l.c., and g.c.-m.s. Pharmacological properties of 5- and R-salsolinol have been compared. Polarography and photocolorimetry and liquid chromatography have been used for analysis of cotarnine. ... 

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