Plasma catecholamines and urinary excretion of their main metabolites in three models of portal hypertension

We have measured, by a specific radioenzymoassay, the plasma concentration of dopamine (DA) and norepinephrine (NE) and by gas chromatography the urinary excretion of some catecholamine metabolites (HVA, homovanillic acid, DOPAC, dihydroxyphenyl acetic acid; VMA, vanilmandelic acid, and DOPEG, dihydroxyphenyl glycol) in three groups of rats with portal hypertension: cirrhotic rats (CR), rats with progressive portal hypertension (PPH) and rats with progressive hepatic congestion (PHC). The three groups of rats had portal hypertension. PPH and PHC had also intrahepatic hypertension. CR rats showed an increased urinary excretion of NE and DA metabolites with a normal plasma concentration of these catecholamines, suggesting an increased turnover of NE and DA in this experimental model. PPH animals had a high plasma DA concentration with a decreased urinary excretion of catecholamine metabolites. PHC showed high plasma DA and NE levels with normal or increased urinary excretion of its metabolites. These results suggest that an increased neural activity is present in the early stages of experimental cirrhosis in rats and this alteration does not seem directly related to the portal hypertension but perhaps to the intrahepatic hypertension or to the hepatocellular damage.     

Catecholamine and thyroid hormone metabolism in a case of anorexia nervosa

Alterations in catecholamine (CA) and thyroid hormone metabolism were examined in a 12-year-old girl with anorexia nervosa during 3 months of treatment. According to her body weight change, the observation period was divided into 3 stages: initial emaciation (stage 1), stable maintenance of the -30% level of the previous weight (stage 2) and convalescent stage (stage 3). Stage 1 was characterized by relatively high urinary norepinephrine (NE) and epinephrine (E) but low dopamine (DA) excretion, elevated plasma DA-beta-hydroxylase (DBH) activity and reduced serum thyroid hormones, especially the triiodothyronine (T3) level. In stage 2, urinary CAs were markedly suppressed, while serum thyroid hormones gradually increase. In stage 3, a great increase in DA excretion, a fall in plasma DBH activity and normalization of thyroid hormones were observed. In the low T3 state below 60 ng/dl, urinary NE + E/DA ratios were elevated and widely fluctuated (0.58 +/- 0.30, SD), but were gradually decreased and completely stabilized in the normal T3 state (0.07 +/- 0.02, P less than 0.001). These results indicate that (1) although total CA production was depressed in anorexia nervosa, a change from an adrenergic-dominant to a dopaminergic-dominant state occurs in accordance with body weight gain, and (2) this shift in the CA profile is associated with concomitant recovery of reduced thyroid hormone concentrations. Thus, as for the energy expenditure, compensatory changes were observed in CAs and thyroid hormones in relation to caloric restriction.     

Effects of dibutyryl cyclic AMP on tyrosine uptake and metabolism in neuroblastoma cultures

A series of thin-layer Chromatographic (TLC) systems were employed to study the effects of dibutyryl cyclic AMP (db-cAMP) on the metabolism of ³H-tyrosine in neuroblastoma cultures. The neuroblastoma monolayer cultures incubated with radiolabelled tyrosine synthesized di-hydroxyphenylalanine (DOPA), dopamine (DA), and norepinephrine (NE), in confirmation of previous reports identifying these compounds in neuroblastoma cultures. In addition, we found evidence suggesting the presence of metabolites of DA and NE, that is, homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) together with 3-methoxy-4-hydroxymandelic acid (VMA). When these cultures were grown in the presence of db-cAMP for 3 days, tyrosine uptake was increased with a proportional increase in tyrosine hydroxylation. This effect persisted in the absence of db-cAMP, but it was not apparent with only 90 min exposure to db-cAMP. Suspension cultures showed the same baseline level of tyrosine uptake as did monolayer cultures, but the uptake in suspension cultures failed to increase with db-cAMP treatment. It is suggested that the db-cAMP induced differentiation of the neuroblastoma cells in monolayer cultures was associated with induction of a tyrosine uptake system.     

Reduction in human urinary MHPG excretion by guanethidine: urinary MHPG as index of sympathetic nervous activity.

The norepinephrine metabolites methoxyhydroxyphenyl glycol (MHPG) and vanillylmandelic acid (VMA) were measured in the urine of hypertensive subjects before and during adminstration of guanethidine, a peripheral sympatholytic agent which does not cross the blood-brain barrier or deplete adrenal catecholamines. Dosages of guanethidine (1.2 mg/kg/day) sufficient to cause at least a 20 torr reduction in standing systolic blood pressure caused a mean 63% (maximum of 68%) reduction in urinary MHPG excretion (p=0.01) while only causing a mean 37% (maximum of 44%) reduction (p<0.005) in excretion of VMA. These results indicate that MHPG in human urine, as in lower animals, is predominantly the product of peripheral sympathetic nervous system, rather than central nervous system nonrepinephrine metabolism. Urinary MHPG is more sensitive to specific sympatholytic therapy than is urinary VMA, and may be a useful index of sympathetic nervous activity.     

Catecholamines increase in the urine of non-segmental vitiligo especially during its active phase

Neural factors appear to play a major role in the pathogenesis of vitiligo. To investigate the possible correlation between vitiligo and peripheral monoaminergic system activity, we used high-pressure liquid chromatography and electrochemical detector methods to evaluate the basal urine excretion values of catecholamines [norepinephrine (NE), epinephrine and dopamine (DA)], their relative metabolites [3-methoxy-4-hydroxyphenylglycol (MHPG), normetanephrine (NMN), metanephrine (MN), vanilmandelic acid (VMA) and homovanillic acid], as well as 5-hydroxyindoleacetic acid (5-HIAA), in 35 healthy subjects and in 70 patients, suffering from non-segmental vitiligo at different stages of the disease. Levels of NE, DA, NMN, MN, MHPG, VMA and 5-HIAA were found to be significantly higher in patients than in controls. The patients with progressive vitiligo (n = 56) presented increased urinary excretion values for all parameters (in particular, NE levels) than other patients. Interestingly, in patients at its more recent vitiligo onset (<1 yr), NE values were different to those of subjects affected from 1 to 5 yr and from 6 to 10 yr. This result was confirmed by the significant negative relationship detected between NE excretion values and disease duration. In both vitiligo and control groups, significant correlations were found between monoamines as well as between these monoamines and their metabolites. The increase in catecholamine turnover, mainly occurring at the onset of the disease, is probably due to the stress associated with the appearance of lesions. Moreover, considering that these compounds readily produce toxic free-radicals and that vitiliginous subjects have a defective free radical defence mechanism, they may also contribute to the disappearance of melanocytes in the early phases of vitiligo.     

Catecholamines Increase in the Urine of Non‐Segmental Vitiligo Especially During Its Active Phase

Neural factors appear to play a major role in the pathogenesis of vitiligo. To investigate the possible correlation between vitiligo and peripheral monoaminergic system activity, we used high‐pressure liquid chromatography and electrochemical detector methods to evaluate the basal urine excretion values of catecholamines [norepinephrine (NE), epinephrine and dopamine (DA)], their relative metabolites [3‐methoxy‐4‐hydroxyphenylglycol (MHPG), normetanephrine (NMN), metanephrine (MN), vanilmandelic acid (VMA) and homovanillic acid], as well as 5‐hydroxyindoleacetic acid (5‐HIAA), in 35 healthy subjects and in 70 patients, suffering from non‐segmental vitiligo at different stages of the disease. Levels of NE, DA, NMN, MN, MHPG, VMA and 5‐HIAA were found to be significantly higher in patients than in controls. The patients with progressive vitiligo (n = 56) presented increased urinary excretion values for all parameters (in particular, NE levels) than other patients. Interestingly, in patients at its more recent vitiligo onset (<1 yr), NE values were different to those of subjects affected from 1 to 5 yr and from 6 to 10 yr. This result was confirmed by the significant negative relationship detected between NE excretion values and disease duration. In both vitiligo and control groups, significant correlations were found between monoamines as well as between these monoamines and their metabolites. The increase in catecholamine turnover, mainly occurring at the onset of the disease, is probably due to the stress associated with the appearance of lesions. Moreover, considering that these compounds readily produce toxic free‐radicals and that vitiliginous subjects have a defective free radical defence mechanism, they may also contribute to the disappearance of melanocytes in the early phases of vitiligo.     

A new approach to biochemical evaluation of brain dopamine metabolism

1. Dopaminergic neurotransmission in brain is receiving increased attention because of its known involvement in Parkinson's disease and new methods for the treatment of this disorder and because of hypotheses relating several psychiatric disorders to abnormalities in brain dopaminergic systems. 2. Chemical assessment of brain dopamine metabolism has been attempted by measuring levels of its major metabolite, homovanillic acid (HVA), in cerebrospinal fluid, plasma, or urine. Because HVA is derived in part from dopamine formed in noradrenergic neurons, plasma levels and urinary excretion rates of HVA do not adequately reflect solely metabolism of brain dopamine. 3. Using debrisoquin, the peripheral contributions of HVA to plasma or urinary HVA can be diminished, but the extent of residual HVA formation in noradrenergic neurons is unknown. By measuring the levels of methoxy-hydroxyphenylglycol (MHPG) in plasma or of urinary norepinephrine metabolites (total MHPG in monkeys; the sum of total MHPG and vanillyl mandelic acid (VMA) in humans) along with HVA, it is possible to estimate the degree of impairment by debrisoquin of HVA formation from noradrenergic neuronal dopamine and thereby better assess brain dopamine metabolism. 4. This method was applied to a monkey before and after destruction of the nigrostriatal pathway by the administration of MPTP.     

Determination of dansylated monoamine and amino acid neurotransmitters and their metabolites in human plasma by liquid chromatography-electrospray ionization tandem mass spectrometry

The determination of neurotransmitters (NTs) and their metabolites facilitates better understanding of complex neurobiology in the central nervous system disorders and has expanding uses in many other fields. We present a liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI/MS/MS) method for the quantification of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine (NE), vanillymandelic acid (VMA), 3-methoxy-4-hydroxy phenylglycol (MHPG), 5-hydroxytryptamine (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA), glutamate (Glu), and γ-aminobutyric acid (GABA). The NTs and their metabolites were dansylated and analyzed by an LC gradient on a C18 column on-line with a tandem mass spectrometer. This method exhibited excellent linearity for all of the analytes with regression coefficients higher than 0.99. The lower limit of quantification (LLOQ) values for DA, DOPAC, HVA, NE, VMA, MHPG, 5-HT, 5-HIAA, Glu, and GABA were 0.57, 0.37, 0.35, 0.40, 0.35, 0.91, 0.27, 0.43, 0.65, and 1.62 pmol/ml, respectively. The precision results were expressed as coefficients of variation (CVs), ranging from 1.5% to 13.6% for intraassay and from 2.9% to 13.7% for the interassay. This novel LC-ESI/MS/MS approach is precise, highly sensitive, specific, and sufficiently simple. It can provide an alternative method for the quantification of the NTs and their metabolites in human plasma.     

Variance in the production of homovanillic acid and 3-methoxy-4-hydroxyphenethyleneglycol by the awake primate brain

Previous experimental results, using a new technique whereby the production rates of the neurotransmitter metabolites homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenethyleneglycol (MHPG) by the awake primate brain are determined, have shown a wide variance in metabolite production among both animal and human subjects. These data suggested that either individual subjects differ in the activity of brain dopamine (DA) or norepinephrine (NE) neurons and/or that the activities of these neurons fluctuate over time. For these reasons a series of experiments were performed in which measures of HVA and MHPG production were obtained at three time points in the same animal (monkeys) over a three hour period. It was found that the group mean values for the production of HVA and MHPG by brain were similar for each of the three time points. However, it was also found that marked variations in HVA and MHPG production occur within a single animal over a three hour period. The coefficients of variation for individual animals for HVA ranged from 9.3 to 31.9% and for MHPG from 10.1 to 62.3%. These variations were not correlated with grossly observable changes in behavioral states. Using an analysis of variance it was found that the variance in MHPG production was significantly greater than that for HVA (F = 6.2, p < 0.05) suggesting that brain NE systems are more liable and/or show greater change than do brain DA systems. These data are interpreted as indicating that in the awake, resting primate brain fluctuations in the activities of DA and NE neurons occur, i.e. there is not a steady, invariant production of metabolites but rather they are produced in pulses of varying lengths. This interpretation of the data is generally consistent with electrophysiological studies which indicate that catecholamine neurons fire in bursts which are then followed by silent periods. Finally, in terms of practical application of the V-A difference technique, these data indicate that replicable group mean estimates of brain HVA and MHPG production can be obtained by averaging values from a single time point whereas accurate information about an individual animal will require multiple samplings.Recent reports from this laboratory have described a method whereby a direct measure of the rates of production of neurotransmitter metabolites such as homovanillic acid (HVA), 3-methoxy-4-hydroxyphenethyleneglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) by the awake primate brain can be determined (1, 2, 3, 4). Since the quantities of HVA, MHPG, and probably 5-HIAA in the brain vary as a function of the activity of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) neurons (1, 5, 6, 7, 8), it is likely that these measures of neurotransmitter metabolite production reflect the functional state of brain DA, NE, and 5-HT neuronal systems. The experimental results thus far obtained with this technique have shown a wide variance in the rates of neurotransmitter metabolite production across both animal and human subjects even though the subjects were not in clearly different behavioral or emotional states (1, 2, 4, 9). These data suggested that either individual subjects differ markedly in the activities of brain DA, NE, and 5-HT neurotransmitter systems and/or that the activity of these systems fluctuates markedly over time. For these reasons, experiments were undertaken in which repeated measures of HVA and MHPG production by brain within the same animal were determined over a three hour period. The results of these experiments, which are reported here, indicate that there are marked changes in brain metabolite production which occur within animals. The implications of these findings for our understanding of the functioning of brain neurotransmitter systems and for the practical applications of this technique are discussed.     

Effect of MPTP-induced parkinsonism in monkeys on the urinary excretion of HVA and MHPG during debrisoquin administration

During debrisoquin administration to three monkeys there were significant reductions in excretion rates of HVA, the major dopamine metabolite, and MHPG, the major norepinephrine metabolite. Excretion rates of HVA were highly correlated to those of MHPG. The regression line relating HVA and MHPG excretion suggests that a portion of HVA (about 25%) is derived from a source independent of norepinephrine metabolites. There was a striking reduction of this portion of HVA excretion after MPTP-induced destruction of dopaminergic nigrostriatal neurons. These results support the view that the rate of HVA formation in brain dopaminergic neurons can be estimated from the relationship of urinary excretion rates of HVA and MHPG before and during debrisoquin treatment.     

Relationship Between Plasma and Cerebrospinal Fluid Norepinephrine and Dopamine Metabolites in a Nonhuman Primate

Major and minor pathways of metabolism in the mammalian CNS result in the formation of 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and normetanephrine (NMN) from norepinephrine (NE), and homovanillic acid (HVA) and 3-methoxytyramine (3-MT) from dopamine (DA), respectively. The correlational relationships between HVA and 3-MT and between MHPG and NMN in primate CSF and plasma have not been described. These relationships may help to elucidate the usefulness of CSF and plasma metabolites as indices of CNS NE and DA activity. In addition, because NMN is unlikely to cross the blood-brain barrier. CSF NMN concentrations would not be confounded by contributions from plasma, which is a major issue with CSF MHPG. We have obtained repeated samples of plasma and CSF from drug-naive male squirrel monkeys and have measured the concentrations of MHPG, HVA, NMN, and 3-MT to define their correlational relationships. For the NE metabolites, significant correlations were obtained for CSF MHPG and NMN (r = 0.806, p less than 0.001), plasma MHPG and CSF NMN (r = 0.753, p less than 0.001), and plasma and CSF MHPG (r = 0.776, p less than 0.001). These results suggest that CSF and plasma MHPG and CSF NMN may reflect gross changes in whole brain steady-state noradrenergic metabolism. Only a single significant relationship was demonstrated for the DA metabolites, with CSF 3-MT correlating with plasma HVA (r = 0.301, p less than 0.025). The results for the DA metabolites probably reflect regional differences in steady-state brain dopaminergic metabolism.     

The effect of probenecid on catecholamine metabolites in human cerebrospinal fluid analyzed by mass fragmentography.

A gas chromatography-mass fragmentography (GC-MS) method was used to measure homovanillic acid (HVA), vanillylmandelic acid (VMA) and 3-methoxy-4-hydroxyphenethylene glycol (MHPG) in lumbar cerebrospinal fluid (CSF) of 31 patients before and after treatment with probenecid. HVA values increased from 24.6 ± 2.6 S.E.M. to 210 ± 17 ng/ml. The increase in VMA was from 1.06 ± 0.23 to 2.22 ± 0.17 ng/ml and that of MHPG was from 12.2 ± 1.08 to 15.6 ± 1.27 ng/ml. All increases were significant (p = < .01). The results for MHPG and HVA are consistent with results of earlier studies using different methods. VMA concentrations increased significantly but at a rate much lower than those of HVA.     

The effect of dietary precursors on the excretion of amines and their metabolites in the rat

The influence of diet on the excretion of catecholamines, some of their metabolites, and pHPG, an octopamine metabolite, was examined. Two groups of rats were fed either a cereal-containing standard laboratory Purina rat chow or a cereal-free casein diet. Use of the standard chow resulted in significant increases in the urinary values for total MHPG, pHPG, DHPE, MHPE, and free and total DOPAC by the seventh day in comparison to the casein diet. No changes were noted in the excretion of free and total NE, DA, and HVA. The data indicate that it is necessary to place the animals on the casein diet several days before determining the excretion of the aforementioned metabolites.     

Effects of Handling or Immobilization on Plasma Levels of 3,4-Dihydroxyphenylalanine, Catecholamines, and Metabolites in Rats

In conscious animals, handling and immobilization increase plasma levels of the catecholamines norepinephrine (NE) and epinephrine (EPI). This study examined plasma concentrations of endogenous compounds related to catecholamine synthesis and metabolism during and after exposure to these stressors in conscious rats. Plasma levels of 3,4-dihydroxyphenylalanine (DOPA), NE, EPI, and dopamine (DA), the deaminated catechol metabolites 3,4-dihydroxyphenylglycol (DHPG), and 3,4-dihydroxyphenylacetic acid (DOPAC), and their O-methylated derivatives methoxyhydroxyphenylglycol (MHPG) and homovanillic acid (HVA) were measured using liquid chromatography with electrochemical detection at 1, 3, 5, 20, 60, and 120 min of immobilization. By 1 min of immobilization, plasma NE and EPI levels had already reached peak values, and plasma levels of DOPA, DHPG, DOPAC, and MHPG were increased significantly from baseline, whereas plasma DA and HVA levels were unchanged. During the remainder of the immobilization period, the increased levels of DOPA, NE, and EPI were maintained, whereas levels of the metabolites progressively increased. In animals immobilized briefly (5 min), elevated concentrations of the metabolites persisted after release from the restraint, whereas DOPA and catecholamine levels returned to baseline. Gentle handling for 1 min also significantly increased plasma levels of DOPA, NE, EPI, and the NE metabolites DHPG and MHPG, without increasing levels of DA or HVA. The results show that in conscious rats, immobilization or even gentle handling rapidly increases plasma levels of catecholamines, the catecholamine precursor DOPA, and metabolites of NE and DA, indicating rapid increases in the synthesis, release, reuptake, and metabolism of catecholamines.     

Kynurenine metabolism in rats: some hormonal factors affecting enzyme activities.

Six male subjects (19–23 years old) underwent a 7-day control period with respect to diet, temperature (22C), and sleep (7.5 hrs), followed by a 2-day exposure to 15C and a 2-day recovery period (22C). Urine collections were made every 8 hours commencing at 2300 hours; MHPG and VMA were assayed using gas-liquid chromatography. During the control period a diurnal rhythmicity was demonstrated for MHPG and VMA with maxima at 0700–1500 hours. The mean excretory rates for MHPG and VMA were 0.71 ± 0.04 μg and 2.6 ± 0.2 μg per milligram creatinine (± S.E.), respectively. Cold exposure abolished the rhythms for MHPG and VMA and caused an 18% increase in MHPG excretion. In contrast, VMA excretion was not altered. Significant correlations were obtained with MHPG excretion and both urinary cortisol and rectal temperature. The data suggest that MHPG excretion may be indicative of changes in norephinephrine metabolism in the central nervous system, although alterations in peripheral degradative pathways cannot be ruled out. Careful interpretation of changes in MHPG excretion in clinical studies is emphasized due to the relative ease of altering MHPG metabolism.     

Catecholamine Glucuronidation: An Important Metabolic Pathway for Dopamine in the Rat

Abstract: In the present study, we found that large quantities of dopamine (DA) glucuronide were present in rat cerebrospinal fluid (CSF), plasma, and urine, whereas the glucuronides of norepinephrine (NE) and epinephrine (E) were almost undetectable. The high urinary excretion of DA glucuronide was in a range comparable to that of homovanillic acid (HVA). Sulfates of DA, NE, and E were measurable in all three body fluids, but only in small quantities. The measured DA glucuronide was predominantly of endogenous origin, as the feeding of sucrose instead of routine diet did not reduce the urinary output of DA glucuronide. Adrenalectomy but not peripheral sympathectomy induced by chronic guanethidine injection substantially decreased plasma DA glucuronide concentrations, indicating that the adrenals serve as an important source of endogenous DA glucuronide. The data suggest that glucuronidation constitutes an important metabolic pathway for endogenous DA of central and peripheral origin in rats; this route, however, is exclusive to DA and appears to play a negligible role for NE and E.     

Effects of chronic brofaromine administration on biogenic amines including sulphatoxymelatonin and acid metabolites in patients with bulimia nervosa

Brofaromine, a selective and reversible inhibitor of monoamine oxidase-A (MAO-A) was given to 19 women while 17 received placebo for 8 weeks. All met DSM III-R criteria for bulimia nervosa, a psychiatric disorder in which uncontrolled overeating episodes are accompanied by purging activities and extreme concerns about body shape and weight. The following indices were measured: plasma and urinary phenylacetic acid (PAA), homovanillic acid (HVA), vanillylmandellic acid (VMA); plasma tryptamine (T), phenylethylamine (PE), and 5-hydroxyindoleacetic acid (5-HIAA) and urinary 6-sulphatoxymelatonin (aMT6s). PE levels remained the same but T showed a trend toward elevation over time. Twenty-four hour levels of urinary aMT6s in BN patients were higher at week 4 when compared to baseline and week 8. There was a significant reduction in plasma VMA and HVA over time during treatment with brofaromine and both plasma HVA and VMA were significantly lower for the brofaromine group compared to placebo at week 4. Plasma 5-HIAA was significantly higher for the brofaromine group after 8 weeks when compared to placebo. Urinary VMA decreased significantly from baseline to week 4 with a partial elevation at 8 weeks. Urinary VMA was also significantly lower in patients on brofaromine at week 4. This study verifies that brofaromine complies with predicted MAO-A inhibiting patterns in a clinical population.     

Free, glucuronide, and sulfate catecholamines in the rat: effect of hypoxia

The formation and excretion of conjugated catecholamines (CA) was studied in conscious rats after sympathetic stimulation by hypoxia (5.5-6% O2, 4 h). Hypoxia induced a rapid and intense increase of free epinephrine (E, X 12) and norepinephrine (NE, X 6) but only a limited enhancement of free dopamine (DA, X 2). Sulfate conjugates of E and NE had kinetics similar to the free forms, while glucuronides were only moderately and lately altered. In contrast to free and sulfated DA, DA glucuronide, the major plasma conjugate, was decreased (-25%). This result suggests that DA glucuronide, unlike other CA conjugates, is not related to detoxication but might supply a CA precursor. Urinary conjugates badly reflected plasma conjugates. In normoxic controls, CA conjugates prevailed in the plasma, whereas the free amines prevailed in the urine. Hypoxia increased mainly the excretion of E and NE glucuronide but not of the free amines. Urinary DA, free or conjugated, was decreased (-25%), a result in keeping with plasma DA glucuronide only. The poor relations between plasma and urine catecholamines pinpoint the importance of the kidney in CA handling.     

Urinary excretion of bioactive amines and their metabolites in psychiatric patients receiving phenelzine

Phenelzine [2-phenylethylhydrazine] (PLZ), a potent inhibitor of monoamine oxidase (MAO)-A and-B, is used widely in psychiatry. We have studied the effects of PLZ administration on urinary excretion of several bioactive amines and their metabolites in psychiatric patients. Urine samples (24-hour) were collected prior to treatment and again at 2 and 4 weeks of treatment with PLZ (30–90 mg daily in divided doses). Amines and metabolites analyzed included 2-phenylethylamine (PEA), m-and p-tyramine (m-and p-TA), phenylacetic acid (PAA), m-and p-hydroxyphenylacetic acid (m-and p-OH-PAA), tryptamine (T), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), normetanephrine (NME), 3-methoxy-4-hydroxyphenylglycol (MHPG), 3-methoxytyramine (3-MT), and homovanillic acid (HVA). Levels of PEA, p-TA, 5-HT, and T were elevated during treatment with PLZ, but no significant changes in urinary excretion of the acid metabolites PAA, p-OH-PAA, and 5-HIAA were observed. Urinary levels of the noradrenaline metabolites NME and MHPG were increased and decreased, respectively; a similar pattern was observed with the dopamine metabolites 3-MT and HVA. There was an elevation in levels of m-TA and a decrease in its acid metabolite m-OH-PAA during the treatment with PLZ.     

Comparative analysis of indices of central dopaminergic functions in man

Various postulated indices of central dopaminergic activity - cerebrospinal fluid (CSF) dopamine (DA), dihydroxy-phenylacetic acid (DOPAC), homovanillic acid (HVA), noradrenaline (NA), plasma NA, serum prolactin, serum dopamine-β-hydroxylase (DBH), and platelet monoamine oxidase (MAO) activity - were measured in 30 drug-free inpatients. The mean values and the ranges were similar to those described in the literature. Plasma NA showed significant positive correlation with age. Significant positive correlation was found between CSF DA and its metabolites DOPAC and HVA. Serum DBH activity showed a slight but significant inverse correlation with CSF DA and its two metabolites. CSF NA showed a significant positive correlation with CSF DOPAC, but only in females. Serum DBH activity had no significant correlation either with CSF or with plasma NA levels. These findings suggest that either CSF HVA or DOPAC and DA may be useful indicators of DA metabolism in humans. Serum DBH activity may be in relationship with the central dopaminergic functions.