The rapid growth and expansion of Master of health professions education (MHPE) programs: A mixed-methods study of international curricular trends and guidelines for programs.

PURPOSE: This study explores international trends and standards of Master's degree programs through a comprehensive environmental scan and focus group interviews to understand curricular structure, content, program director expectations, educational context, and future directions. METHOD: Authors conducted a two-phase mixed-methods sequential explanatory design to conduct the environmental scan (phase 1), and subsequently conducting focus groups (phase 2) with program directors. A population list of Master's programs was used to generate a sampling frame, considering the geographic region (continent) and institution type (university, organization, public institution). Qualitative data were coded to analyze the breadth and depth of courses. Three one-hour virtual focus group interviews were conducted with ten program directors. RESULTS: The population list of 159 Masters programs worldwide was used to create a sample for analysis in the environmental scan (n = 46 Masters programs), representing programs from North America, Europe, Australia, and South Africa. Most programs (39%) delivered their courses online, with 20% exclusively offering an in-person program. Focus group participants indicated expectations of graduates, context in which they learn, as well as future directions for improving health professions education graduate programs. CONCLUSION: Program directors should consider programmatic aims, localized needs, and quality/standard of the program in designing Masters programs, with individualized growth opportunities for learners.

Creation and Initial Validation of the Mayo Outpatient Precepting Evaluation Tool.

BACKGROUND AND OBJECTIVES: Preceptors in family medicine residencies need feedback to improve. When we found no validated, behavior-based tool to assess the outpatient precepting of family medicine residents, we sought to fill this gap by developing and initially validating the Mayo Outpatient Precepting Evaluation Tool (MOPET). METHODS: To develop the MOPET, we applied the Stanford Faculty Development Program (SFDP) theoretical framework for education, more recent work on peer review of medical teaching, and expert review of items. The residency behavioral scientist and a volunteer physician independently completed the MOPET while co-observing a precepting physician during continuity clinic sessions (N=20). We assessed the tool's validity via interrater reliability and cross-validation with the SFDP-26. RESULTS: The tool demonstrated high interrater reliability for the following effective teaching behaviors: (a) allowing the resident to present without interrupting, (b) encouraging the formulation of a goal, (c) checking in on the resident's goal, (d) using multimodal teaching aids, (e) asking to discuss the differential diagnosis, (f) asking to discuss alternative management, (g) encouraging the resident to pursue literature and/or other resources, and (h) reinforcing self-directed learning. The MOPET measures strongly correlated with most items from the SFDP-26, indicating good cross-validity. CONCLUSIONS: The MOPET is a theoretically sound, behavior-based, reliable, and initially validated tool for peer review of outpatient family medicine resident teaching. This tool can support faculty development in outpatient clinical learning environments.

Tuition Costs of Master's of Health Professions Education Programs: A Cross-Sectional Analysis.

PURPOSE: The increasing professionalization of medical education during the past 2 decades has ushered in an era in which formal degrees, particularly master's of health professions education (MHPE), have become important for career advancement in medical education. Although tuition costs can pose a substantial barrier for many seeking advanced degrees in health professions education, data on tuition associated with these programs are lacking. This study examines the accessibility of pertinent cost-related information available to prospective students and the variability of costs among programs worldwide. METHOD: The authors conducted an Internet-based, cross-sectional study, augmented with emails and direct contact with educators, to extract tuition-related data for MHPE programs between March 29, 2022, and September 20, 2022. Costs were converted to an annual total within each jurisdiction's currency and converted to U.S. dollars on August 18, 2022. RESULTS: Of the 121 programs included in the final cost analysis, only 56 had publicly available cost information. Excluding programs free to local students, the mean (SD) total tuition cost was $19,169 ($16,649), and the median (interquartile range) cost was $13,784 ($9,401- $22,650) (n = 109). North America had the highest mean (SD) tuition for local students ($26,751 [$22,538]), followed by Australia and New Zealand ($19,778 [$10,514]) and Europe ($14,872 [$7,731]), whereas Africa had the lowest ($2,598 [$1,650]). The region with the highest mean (SD) tuition for international students was North America ($38,217 [$19,500]), followed by Australia and New Zealand ($36,891 [$10,397]) and Europe ($22,677 [$10,010]), whereas Africa had the lowest ($3,237 [$1,189]). CONCLUSIONS: There is substantial variability in the geographic distribution of MHPE programs and marked differences in tuition. Incomplete program websites and limited responsiveness from many programs contributed to a lack of transparency regarding potential financial implications. Greater efforts are necessary to ensure equitable access to health professions education.

Plasma variations in stress markers: Clinical trial of two anesthetics used in regional block in the extraction of impacted inferior third molars

OBJECTIVES: Was to evaluate the effect of different regional anesthetics (articaine with epinephrine versus prilocaine with felypressin) on stress in the extraction of impacted lower third molars in healthy subjects. Sutdy Desing: A prospective single-blind, split-mouth cross-over randomized study was designed, with a control group. The experimental group consisted of 24 otherwise healthy male volunteers, with two impacted lower third molars which were surgically extracted after inferior alveolar nerve block (regional anesthesia), with a fortnight's interval: the right using 4% articaine with 1:100.000 epinephrine, and the left 3% prilocaine with 1:1.850.000 fely-pressin. Patients were randomized for the first surgical procedure. To analyze the variation in four stress markers, homovanillic acid, 3-methoxy-4-hydroxyphenylglycol, prolactin and cortisol, 10-mL blood samples were obtained at t = 0, 5, 60, and 120 minutes. The control group consisted of 12 healthy volunteers, who did not undergo either extrac-tions or anesthetic procedures but from whom blood samples were collected and analyzed in the same way. RESULTS: Plasma cortisol increased in the experimental group (multiple range test, P<0.05), the levels being sig-nificantly higher in the group receiving 3% prilocaine with 1:1.850,000 felypressin (signed rank test, p < 0.0007). There was a significant reduction in homovanillic acid over time in both groups (multiple range test, P<0.05). No significant differences were observed in homovanillic acid, 3-methoxy-4-hydroxyphenylglycol or prolactin con-centrations between the experimental and control groups. CONCLUSIONS: The effect of regional anesthesia on stress is lower when 4% articaine with 1:100,000 epinephrine is used in this surgical procedure

Naturally occurring phenylethanoid glycosides: potential leads for new therapeutics.

Natural products have long been regarded as excellent sources for drug discovery given their structure diversity and wide variety of biological activities. Phenylethanoid glycosides are naturally occurring compounds of plant origin and are structurally characterized with a hydroxyphenylethyl moiety to which a glucopyranose is linked through a glycosidic bond. To date several hundred compounds of this type have been isolated from medicinal plants and further pharmacological studies in vitro or in vivo have shown that these compounds possess a broad array of biological activities including antibacterial, antitumor, antiviral, anti-inflammatory, neuro-protective, antioxidant, hepatoprotective, immunomodulatory, and tyrosinase inhibitory actions. Given their extensive activity profile, structure-activity relationships analyses of these compounds have been performed in a number of studies to reveal potential leads for future drug design. This article will summarize the major developments in phenylethanoid glycosides-based research in the past decade. The progresses made in phytochemistry and biological activity studies of these compounds will be reviewed. Particular attention will be given to the novel structures identified to date and the prominent therapeutic values associated with these molecules.

Queen pheromone blocks aversive learning in young worker bees.

Queen mandibular pheromone (QMP) has profound effects on dopamine signaling in the brain of young worker honey bees. As dopamine in insects has been strongly implicated in aversive learning, we examined QMP's impact on associative olfactory learning in bees. We found that QMP blocks aversive learning in young workers, but leaves appetitive learning intact. We postulate that QMP's effects on aversive learning enhance the likelihood that young workers remain in close contact with their queen by preventing them from forming an aversion to their mother's pheromone bouquet. The results provide an interesting twist to a story of success and survival.

Disminución de la actividad noradrenérgica durante el tratamiento en pacientes bipolares: independencia de los polimorfismos de la COMT / Reduction of noradrenergic activity during treatment in bipolar patients independent from COMT polymorphisms

Introducción: Los estudios más recientes apoyan la idea de que la fisiopatología del síndrome bipolar se sustenta en diversas interacciones de varios sistemas de neurotransmisión. Datos clínicos y preclínicos sugieren también que la actividad noradrenérgica está elevada en estos pacientes antes del tratamiento. Método: En nuestro estudio se ha medido la concentración plasmática del 3-metoxi-4-hidroxifenilglicol (MHPG), principal metabolito de la noradrenalina (NA), en 50 pacientes bipolares tipo I, 29 varones y 21 mujeres, diagnosticados según el Diagnostic and Statistical Manual of Disorders (DSM-IV). También se determinaron los polimorfismos Val108/158Met de la catecol-O-metiltransferasa (COMT). Los pacientes se trataron con olanzapina, a la que posteriormente se añadió litio. Resultados y conclusiones: El tratamiento demostró ser eficaz, tanto en pacientes psicóticos como en no psicóticos; y no se encontró una relación significativa entre los polimorfismos estudiados de la COMT y la respuesta clínica medida por la escala de Young para la manía. Sí se puso de manifiesto una correlación significativa y positiva entre los valores plasmáticos de MHPG antes del tratamiento y después de 3 días de tratamiento con la respuesta a éste

Introduction: Recent studies support the notion that the pathophysiology of bipolar disorder is probably mediated through multiple interactions among neurotransmitter pathways. Preclinical and clinical data also suggest an elevated noradrenergic activity in the brains of these patients before treatment. Methods: We measured the plasma concentration of 3-methoxy-4 hydroxyphenylglycol (MHPG), the principal metabolite of norepinephrine, and determined the Val108/158Met polymorphism of catechol-O-methyltransferase (COMT) in 50 patients (29 men and 21 women) diagnosed with bipolar I disorder according to DSM-IV criteria. The patients were treated with olanzapine with subsequent addition of lithium. Results and conclusions: Overall the treatment was efficacious in both psychotic and non-psychotic patients. No significant associations were found between COMT polymorphism and treatment response (assessed with the Young scale for mania). However, a significant and positive correlation was found between plasma MHPG levels before treatment (and after 3 days of treatment) and clinical outcomes

Antagonism between olive oil phenolics and nitric oxide on lymphomonocyte cytosolic calcium.

Some biological actions of olive oil phenolics (inhibition of platelet aggregation, decrease of LDL-oxidation, inhibition of bacterial growth and hypertensive action) have been attributed to NOS stimulation in endothelial cells through an increase of cytosolic calcium, notwithstanding the scavenging activity of phenolics on NO and superoxide. In this paper, we determine the concentration of cytosolic calcium in human lymphomonocytes incubated with high concentrations of NO-donors (CysNO) and we evaluate the effects of olive oil phenolics on this parameter. CysNO induces a marked decrease of cytosolic calcium; both olive oil phenolics oppose this action of CysNO. The effects of phenolics and CysNO are independent and additive.

Correlations between P300 components and neurotransmitters in the cerebrospinal fluid.

P300 and cerebrospinal fluid neurotransmitter metabolites and amino acids were examined in 10 patients with Alzheimer's disease, 9 patients with vascular dementia and 10 healthy controls. A negative correlation between P300 amplitude and MHPG concentration, negative correlation between P200 and N200 latencies and norepinephrine concentration, positive correlation between N200 latency and lysine concentration and positive correlation between N100 amplitude and tyrosine concentration were statistically significant. These findings suggest that the noradrenergic system influences P300 amplitude, and that multiple systems may influence P300 components.

Effects of continuous and intermittent cold (SART) stress on sympathoadrenal system activity in rats.

We compared sympathoadrenal responses to intermittent cold (SART) stress (in which cold exposure is interrupted by 4-hourly intervals daily at room temperature) with those to continuous cold (-3 degrees C) stress. Plasma levels of dihydroxyphenylalanine (DOPA), catecholamines and their metabolites as well as tyrosine hydroxylase (TH) activities in sympathetically innervated tissues were examined in rats exposed to each stressor for 1 day or for 5 days. Neither SART nor continuous exposure to cold for 1 day or 5 days altered plasma epinephrine (EPI) levels. However, norepinephrine (NE) and dihydroxyphenylglycol (DHPG) levels increased markedly during exposure to these stressors. On the first day of SART or continuous cold stress, NE levels were increased similarly, but the increments in DHPG levels were greater during SART stress. Since DHPG is formed in neurons, neural reuptake of NE may be more enhanced on the first day of SART stress than on the first day of continuous cold stress. After 5 days of SART stress plasma NE levels were significantly higher than those found after 5 days of continuous cold exposure. Plasma levels of DHPG were elevated to the same extent in both 5 days SART- and continuously cold-stressed rats, whereas plasma levels of methoxyhydroxyphenylglycol (MHPG) increased only by 5 days SART stress. Even at 1 h after the removal from 5 days SART stress, increased plasma levels of NE, DHPG and MHPG were still evident. These results suggest that 5 days SART stress elevates extraneuronal O-methylation of DHPG, and that NE turnover is more greatly increased by SART stress than by continuous cold stress. Plasma levels of DOPA, dopamine, dihydroxyphenylacetic acid and homovanillic acid also increased after either SART or continuous cold stress for 1 day and 5 days. Adrenal TH activities were significantly increased in rats exposed to SART or continuous cold stress for 1 day and 5 days, but in brown fat TH activity was elevated only in rats exposed to 5 days of continuous cold. Both SART and continuous cold stress are selective and potent stimuli for activation of the sympathoneural system, apparently without significant adrenomedullary EPI release. The increase of TH activity in the brown fat pad as well as of plasma NE and its metabolites is probably a result of adaptation to cold. It appears that even short intervals of return to a normal environmental temperature, as in SART, are sufficient to diminish sympathetic adaptation to cold.

Effects of neuroleptic treatment on cortisol and 3-methoxy-4-hydroxyphenylethyl glycol levels in blood.

Plasma cortisol and serum 3-methoxy-4-hydroxyphenylethyl glycol (MHPG) were determined before and after 5-6 weeks of neuroleptic treatment in patients with schizophrenia. Following drug treatment both plasma cortisol and serum MHPG levels in patients decreased and plasma cortisol levels were also lower than in unmedicated healthy controls. Indications of a relationship between the reduction of cortisol and MHPG levels were found. The data show that neuroleptic drug treatment inhibits cortisol secretion. It is speculated that this inhibition could be related to reduced noradrenergic activity.

Lack of autoreceptor mediated regulation of the spontaneous dopamine turnover in the isolated neurointermediate lobe of the rat pituitary gland in vitro.

Isolated neurointermediate lobes of the rat pituitary gland were incubated in Krebs-HEPES solution and the spontaneous outflow of endogenous dopamine and its metabolites (DOPAC, HVA and MOPET) was determined by HPLC with electrochemical detection. The spontaneous outflow of dopamine metabolites (about 1500 fmol/10 min) largely exceeded that of dopamine (about 60 fmol/10 min). Apomorphine concentration-dependently (IC50, 205 nmol/l) reduced the spontaneous outflow of the dopamine metabolites. The effect of apomorphine developed slowly and was progressive over an observation period of 70 min. After 1 h of exposure to a maximall effective concentration of apomorphine (10 mumol/l), the outflow of metabolites was inhibited by 43%. The effect of apomorphine was not affected by the dopamine D2 receptor antagonist (-)-sulpiride nor by the dopamine D1 receptor antagonist SCH 23390. Neither quinpirole nor fenoldopam significantly affected the spontaneous outflow of dopamine metabolites. It was previously shown that the high rate of spontaneous outflow of dopamine metabolites from the dopaminergic nerves in the neurointermediate lobe reflects largely the immediate catabolism of newly synthesized dopamine. This high rate of spontaneous dopamine synthesis in the neurointermediate lobe is not controlled by dopamine autoreceptors. Apomorphine appears to inhibit the spontaneous dopamine turnover by an inhibition not mediated by dopamine receptors.

[Effects of thyrotropin-releasing hormone on neurologic recovery and biogenic amine metabolites of cerebrospinal fluid in spinal disorders].

The pharmacological effects of the thyrotropin-releasing hormone (TRH) in relation to biogenic amine metabolism in cerebrospinal fluid were examined in 35 patients with various spinal disorders. Neurologic conditions before and after TRH treatment were evaluated using subjective symptoms and Frankel's classification. Biogenic amine metabolism in cerebrospinal fluid was examined before and after TRH treatment measuring the metabolites by high performance liquid chromatography with electrochemical detection. Significant decreases in metabolites of norepinephrine and dopamine were seen in most cases of spinal disorders. The amount of serotonin metabolite, however, was not changed. In many acute cases, the neurologic condition was improved, and a significant increase in the dopamine metabolite was seen in the improved cases after TRH treatment. In chronic cases, TRH treatment was not as effective as in acute cases. TRH was therefore thought to be an effective agent in the treatment of acute spinal disorders. When an increase in the dopamine metabolite is seen after TRH treatment, neurologic improvement would probably be expected.

The role of cytoplasmic (newly synthesized) dopamine for the spontaneous and electrically evoked release of dopamine and its metabolites from the isolated neurointermediate lobe of the rat pituitary gland in vitro.

Isolated rat NILs were incubated in Krebs-HEPES solution. The release of dopamine and its metabolites (DOPAC, HVA and MOPET) was determined by HPLC with electrochemical detection. The spontaneous release of the sum of metabolites was about 40 times that of dopamine. The spontaneous outflow of dopamine metabolites was unaffected after inhibition of dopamine uptake (by GBR 12921) or after pretreatment with reserpine (5 mg/kg, 12 h before the experiments), but it was reduced by 50% after preincubation with the irreversible DOPA decarboxylase inhibitor, (MFMD, 10 microM, for 10 min). The combination of pretreatment with reserpine and preincubation with MFMD resulted in an 80% inhibition of the spontaneous outflow of dopamine metabolites. Treatment with reserpine caused a 98% depletion of the dopamine tissue content, whereas 60 min after exposure to MFMD the dopamine tissue content was decreased by 40%. Electrical stimulation of the pituitary stalk (3-15 Hz, in the presence of GBR 12921) caused a frequency-dependent release of dopamine. Stimulation at 7 or 15 Hz caused also a significant release of dopamine metabolites. After pretreatment with reserpine, the release of dopamine evoked by stimulation at 15 Hz was abolished, whereas the evoked release of the metabolites was only reduced by about 55%. After MFMD, the evoked release of dopamine decreased by a percentage similar to that of dopamine tissue content, but the reduction of the evoked release of metabolites was more pronounced. In conclusion, the spontaneous release of dopamine metabolites from the dopaminergic nerve endings in the NIL largely reflects the catabolism of newly synthesized dopamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Human class I alcohol dehydrogenases catalyze the interconversion of alcohols and aldehydes in the metabolism of dopamine.

The class I human liver alcohol dehydrogenases (ADHs) catalyze the interconversion of the intermediary alcohols and aldehydes of dopamine metabolism in vitro, whereas those of the class II and class III do not. The individual, homogeneous class I isozymes oxidize (3,4-dihydroxyphenyl)ethanol and (4-hydroxy-3-methoxyphenyl)ethanol (HMPE) and ethanol with kcat/Km values in the range from 16 to 240 mM-1 min-1 and from 16 to 66 mM-1 min-1, respectively. They reduce the corresponding dopamine aldehydes (3,4-dihydroxyphenyl)acetaldehyde and (4-hydroxy-3-methoxyphenyl)acetaldehyde (HMPAL) with kcat/Km values varying from 7800 to 190,000 mM-1 min-1, considerably more efficient than the reduction of acetaldehyde with kcat/Km values from 780 to 4900 mM-1 min-1. For beta 1 gamma 2 ADH, ethanol competes with HMPE oxidation with a Ki of 23 microM. In addition, 1,10-phenanthroline inhibits HMPE oxidation and HMPAL reduction with Ki values of 20 microM and 12 microM, respectively, both quite similar to that for ethanol, Ki = 22 microM. Thus, both ethanol/acetaldehyde and the dopamine intermediates compete for the same site of ADH, a basis for the ethanol-induced in vivo alterations of dopamine metabolism.

Release of endogenous 3,4-dihydroxyphenylethylamine and its metabolites from the isolated neurointermediate lobe of the rat pituitary gland. Effects of electrical stimulation and of inhibition of monoamine oxidase and reuptake.

Isolated rat neurointermediate lobes were incubated in vitro. The release of 3,4-dihydroxyphenylethylamine (dopamine, DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and methoxyphenylethanol (MOPET) was determined by HPLC with electrochemical detection. Under resting conditions, the outflow of metabolites was 35-50 times that of DA. HVA accounted for 50%, DOPAC for 45%, and MOPET for 5% of the metabolites. Although an equivalent of 40-50% of the tissue DA content was released per hour as metabolites, the tissue DA content was not reduced after 110 min of incubation. The spontaneous outflow of DA and its metabolites was not affected by the DA uptake inhibitor GBR 12921 (100 nM). Pargyline (10 microM) caused a time-dependent decrease of all metabolites (up to 90%). In the presence of GBR 12921 and pargyline, the spontaneous outflow of DA increased sevenfold. Removal of the intermediate lobe caused a 78% reduction in tissue DA content and a corresponding reduction of the outflow of metabolites. Electrical stimulation of the pituitary stalk (0.2 ms, 10 V, 15 Hz, three times for 1 min at intervals of 1 min) induced an increase in outflow of DA and all metabolites. DA accounted for 15%, HVA for 41%, DOPAC for 32%, and MOPET for 12% of the evoked release. The electrically evoked release of DA increased fourfold in the presence of GBR 12921 or pargyline and the effects of both drugs were additive. The evoked release of metabolites was not significantly affected by GBR 12921 but completely abolished by pargyline. In conclusion, oxidative deamination and O-methylation are important pathways for the catabolism of DA in the neurointermediate lobe.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo analysis of dopamine and its metabolites in the caudate nucleus during euthermia and hibernation.

Golden-mantled ground squirrels (Citellus lateralis) were chronically implanted with a unilateral push-pull cannula in the caudate nucleus. Perfusates obtained in these unanesthetized, unrestrained animals during the euthermic (non-hibernating) and hibernating states were analyzed for dopamine (DA) and its metabolites (homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 3-methoxy-4-hydroxyphenethanol (MOPET) using high performance liquid chromatography with electrochemical detection. The data revealed clear differences in the performance of the caudate DA system in the two states. During the euthermic state, DA metabolism was indicative of a constant and high turnover rate. Free DA was not detectable in the majority of samples, HVA was detected at consistently high levels, and DOPAC and conjugated DA were present at low levels. By contrast, DA metabolism was sharply altered during hibernation. Free DA was present at high concentrations and HVA concentrations were low. DOPAC was not detected in any sample whereas MOPET was present in all samples. Conjugated DA was present at high concentrations during the second half of the hibernation bout. The shift in the post-release disposition of DA could enhance the stability of DA receptors (i.e. prevent supersensitivity) during the prolonged periods of reduced neural activity typical of hibernation.

Effects of debrisoquin on the excretion of catecholamine and octopamine metabolites in the rat and guinea pig.

The effects of debrisoquin, administered daily for 4 days to rats (40 mg/kg, i.p.) and guinea pigs (4 mg/kg, i.p.), were determined for urinary excretion of several acidic and neutral amine metabolites, including the norepinephrine metabolites, 3-methoxy-4-hydroxyphenethylene glycol (MHPG) and vanillylmandelic acid (VMA), the dopamine metabolites, 3,4-dihydroxyphenethanol (DHPE), 3-methoxy-4-hydroxyphenethanol (MHPE), and homovanillic acid (HVA), and the octopamine metabolite, p-hydroxyphenylglycol (pHPG). The excretion of MHPG was reduced to 32% of control in rats and to 46% in guinea pigs, HVA was reduced to 64 and 80% in these two species, respectively, and MHPE was lowered to 59% of control in the rat but was not affected in the guinea pig. DHPE and pHPG were not altered significantly in either species. VMA was a minor metabolite in both species, being less than 6% of MHPG, and its formation was blocked only partially (rat) or not at all (guinea pig) by debrisoquin. The data refute the idea based on previous in vitro studies that VMA is a major metabolite of norepinephrine in the periphery of the guinea pig as it is in man.

Effects of intraventricular injections of 6-hydroxydopamine on amine metabolites in rat brain and urine.

The effects in rats of intraventricular injections of 6-hydroxydopamine (6-OHDA) on the urinary excretion 1-3 weeks later of 3-methoxy-4-hydroxyphenethylene glycol (MHPG), 3,4-dihydroxyphenethanol (DHPE), 3-methoxy-4-hydroxyphenethanol (MHPE), p-hydroxyphenylglycol (pHPG), homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were examined. The excretion of MHPG was decreased to 63 and 71% of control on days 7 and 14, respectively, but had returned to control levels by day 23, even though the brain levels were decreased by 87%. Free and total HVA excretion was reduced on both days 7 and 23, but free and total DOPAC was reduced only on day 7. Based on these data, it can be estimated that about 39% of the free and 46% of the total HVA in urine originates in the CNS. The excretion of conjugated HVA was decreased by 70-80%, but this decrease does not support the notion that the conjugated form of HVA is derived principally from the brain and thus serves as a better marker of brain dopamine metabolism, since the level of this metabolite in the brain was not correspondingly decreased but was instead increased. Urinary DOPAC levels were generally more variable and derived to a greater extent from the periphery; therefore, DOPAC appears to be less suitable than HVA as a marker of brain dopamine. The results also indicate that as much as 35% of the urinary MHPG may originate in the CNS, although compensatory changes in catecholamine metabolism in either the brain or in the periphery may have somewhat influenced this estimate. The results also suggest that at least as much pHPG as MHPG in urine derives from the CNS. The data are consistent with the idea that the neutral dopamine metabolites largely derive from the brain, but the relatively small depletion in their brain levels produced by 6-OHDA prevented the exact proportion being determined accurately.