Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Droxidopa”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1994

[Study on the metabolism of droxidopa in humans].

Supplement of the deficient neurotransmitters is one of the most effective therapies for neurodegenerative disorders. For the treatment of Parkinson's disease, L-DOPA therapy has been applied to replace dopamine, and droxidopa (L-threo-3,4-dihydroxyphenylserine) therapy to supply noradrenaline (NA). Droxidopa, an artificial amino acid, is decarboxylated by aromatic L-amino acid decarboxylase (AADC) into NA. By application for Parkinson's disease, it alleviated neurological symptoms such as freezing phenomenon, which are refractory to L-DOPA. However, as a precursor of a monoamine, droxidopa was found to be not so effective as L-DOPA; and the clinical efficiency of droxidopa is variable among patients. The metabolic pathway of droxidopa in the brain was examined using human materials. The intraventricular fluid of patients treated with droxidopa, and of control was analyzed by high-performance liquid chromatography with multi-eletrochemical detection (Neurochem). In the intraventricular fluid of the patients treated, free NA concentration increased to be 5.67 +/- 3.40 nM from non-detectable level in the control patients. The patients with higher free NA levels clinically responded better to droxidopa. However, free NA levels varied among patients; and the mechanism of the individual variance should be clarified. In the intraventricular fluid, in addition to NA, a large amount of a metabolite of droxidopa by catechol-O-methyltransferase (COMT), 3-O-methoxy-droxidopa (3OMD), was detected, followed by the metabolites by DOPS-aldolase (DOPS-ALD), protocatechualdehyde and protocatechuic acid. It indicates that considerable parts of administered droxidopa are catabolized by COMT and DOPS-ALD, but not by AADC.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗
PubMed1994

[The effect of droxidopa on the monoamine metabolsim in the human brain].

Droxidopa (L-threo-3,4-dihydroxyphenylserine) is an artificial amino acid, which is used to supplement noradrenaline (NA) in neurodegenerative disorders. Droxidopa is decarboxylated into NA by aromatic L-amino acid decarboxylase in the brain, but its effects on other monoamine neurotransmitters, such as dopamine (DA) and serotonin (5-HT) have not been systematically examined. The monoamine metabolism has been suggested to interact with each other in the brain, and by analysis of the cerebrospinal fluid, L-DOPA, a precursor amino acid used for supplement of DA, was found to inhibit serotonin synthesis in the brain. To examine the effects of droxidopa on the monoamine metabolism, the intraventricular fluid of the patients administered with droxidopa and L-DOPA was analyzed. The levels of monoamines, their precursor amino acids, and their metabolites were compared between the patients administered with L-DOPA. In the patients administered by droxidopa and L-DOPA, droxidopa was shown to increase the concentrations of monoamines (NA, DA and 5-HT), but the difference was not statistically significant by comparison with those treated by L-DOPA alone. The metbolites of DA and 5-HT by monoamine oxidase, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) were also found to increase by droxidopa administration. On the other hand, the metabolites of NA and DA by catechol-O-methyltransferase (COMT), normetanephrine (NMN) and 3-methoxytyramine (3-MT), decreased in the patients treated with droxidopa and L-DOPA compared with the patients administered with L-DOPA alone and control patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2000

Effect of midodrine on chlorpromazine-induced orthostatic hypotension in rabbits: comparison with amezinium, etilefrine and droxidopa.

Orthostatic hypotension was produced in urethane-anesthetized rabbit by a combination of chlorpromazine (0.1 mg/kg, i.v.) and 45 degrees head-up tilt. The effect of midodrine (1 and 3 mg/kg, i.d.) was investigated in comparison with amezinium (10 and 30 mg/kg, i.d.), etilefrine (10 and 30 mg/kg, i.d.) and droxidopa (30 and 100 mg/kg, i.d.). The higher doses of each drug significantly mitigated the chlorpromazine-induced orthostatic hypotension, while none of the lower doses caused a significant effect. The effect of midodrine developed most rapidly; a significant effect was observed 25 min after administration. The order of onset time was midodrine < etilefrine < amezinium < droxidopa. The effect of droxidopa was significant only at 130 to 160 min after administration. The amplitude of effect was in the following order; midodrine = droxidopa > or = etilefrine > amezinium. Midodrine (3 mg/kg, i.d.) mitigated orthostatic hypotension induced by prazosin (0.1 mg/kg, i.v.), but not by pentolinium (0.6 mg/kg, i.v.). It is suggested that midodrine competes with chlorpromazine at alpha1-adrenoceptors and subsequently recovers reflex vasoconstriction. Midodrine may be useful to protect patients with impaired baroreflex activity from accidental orthostatic hypotension during treatment with neuroleptics.

Adrenergic alpha-Agonists↗
PubMed2001

L-threo-dihydroxyphenylserine (L-threo-DOPS; droxidopa) in the management of neurogenic orthostatic hypotension: a multi-national, multi-center, dose-ranging study in multiple system atrophy and pure autonomic failure.

This study was designed to determine the efficacy and tolerability of increasing doses of L-threo-dihydroxyphenylserine (L-threo-DOPS) in treating symptomatic orthostatic hypotension associated with multiple system atrophy (MSA) and pure autonomic failure (PAF). Following a one-week run-in, patients (26 MSA; 6 PAF) with symptomatic orthostatic hypotension received increasing doses of L-threo-DOPS (100, 200 and 300 mg, twice daily) in an open, dose-ranging study. Incremental dose adjustment (after weeks two and four of outpatient treatment) was based on clinical need until blood pressure (BP), and symptoms improved. Final dosage was maintained for six weeks. With L-threo-DOPS, systolic BP decrease was reduced during orthostatic challenge (-22+/-28 mm Hg reduction from a baseline decrease of 54.3+/-27.7 mm Hg, p = 0.0001, n = 32; supine systolic BP at final visit was 118.9+/-28.2 mm Hg). By the end of the study, 25 patients (78%) improved, and in 14 patients (44%) orthostatic hypotension was no longer observed. Decreased orthostatic systolic BP decrease occurred in 22% (7/32), 24% (6/25) and 61% (11/18) of patients treated with 100, 200, and 300 mg L-threo-DOPS twice daily, respectively. An improvement occurred in symptoms associated with orthostatic hypotension, such as light-headedness, dizziness (p = 0.0125), and blurred vision (p = 0.0290). L-threo-DOPS was well tolerated, with the 2 serious adverse events reported being a possible complication of the disease under study, and with no reports of supine hypertension. In conclusion, L-threo-DOPS (100, 200, and 300 mg, twice daily) was well tolerated. The dosage of 300 mg twice daily L-threo-DOPS seemed to offer the most effective control of symptomatic orthostatic hypotension in MSA and PAF.

Adolescent↗
PubMed1991

A case of syndrome of inappropriate secretion of antidiuretic hormone associated with diabetes mellitus.

A 46-year-old man, presenting with headache, nausea, and lassitude, was diagnosed as having diabetes mellitus and hyponatremia, and admitted to Tohoku University Hospital. Insulin treatment improved the hyperglycemia but aggravated hyponatremia, which was proved to be elicited by the inappropriate secretion of antidiuretic hormone (SIADH). An acute water load failed to suppress ADH release in the supine posture but slightly increased plasma atrial natriuretic peptide (ANP). On the other hand, plasma ADH markedly increased in response to an upright posture, accompanied by a fall in blood pressure and a rise in heart rate. After treatment with droxidopa "a sympathomimetic drug", ambulatory blood pressure gradually increased and hyponatremia disappeared. However, blood pressure and ADH responses to upright posture were not improved by treatment with the drug. Moreover, plasma ADH was still not sufficiently suppressed by acute water loading in the supine position, but plasma ANP markedly increased, thereby resulting in urinary dilution and natriuresis. These results suggest that exaggerated ADH release (SIADH) was brought about by the baroreceptor reflex stimulated by the postural hypotension, and also by the impaired osmoregulation associated with diabetic neuropathy, and that droxidopa improved cardiovascular function and increased ANP release with resultant urinary dilution and natriuresis in spite of slightly increased ADH release.

Blood Pressure↗
PubMed1994

The noradrenaline precursor L-threo-3,4-dihydroxyphenylserine exhibits antinociceptive activity via central alpha-adrenoceptors in the mouse.

1. Systemic (s.c. or p.o.) administration of L-threo-3,4-dihydroxyphenylserine (droxidopa, L-threo-DOPS; L-DOPS), a noradrenaline precursor, at a dose-range of 100-800 mg kg-1, produced naloxone-resistant antinociception in a dose-dependent manner in the mouse, as assessed by the tail flick test, kaolin-induced writhing test and formalin-induced nociception test. 2. Antinociception elicited by L-DOPS (400 mg kg-1, s.c.) was not affected by s.c. injection of benserazide, a peripherally preferential L-aromatic amino acid decarboxylase inhibitor, but was suppressed by its intracerebroventricular (i.c.v.) injection. 3. I.c.v. or intrathecal (i.t.) administration of the non-selective alpha-blocker, phentolamine, significantly reduced L-DOPS-induced antinociception. 4. I.c.v. administration of the alpha 1-blocker, prazosin, but not the alpha 2-blocker, yohimbine, abolished the antinociceptive effects of L-DOPS. In contrast, both blockers, when administered i.t., exhibited significant inhibitory effects. 5. These results suggest that systemic L-DOPS produces opioid-independent antinociception, mediated by supraspinal alpha 1-adrenoceptors and by spinal alpha 1- and alpha 2-adrenoceptors and may predict additional therapeutic applications of L-DOPS as an analgesic.

Administration, Oral↗
PubMed2005

[Simple method for precognition of drug interaction between oral iron and phenolic hydroxyl group-containing drugs].

In the present study, we devised a simple method for detecting the drug interaction between oral iron preparations and phenolic hydroxyl group-containing drugs, using the coloring reaction as indicator, due to the formation of complexes or chelates. In the method, oral iron preparations and test drugs in amounts as much as single dose for adults were added to 10 ml of purified water to make sample suspensions for testing. Thirty minutes after mixing an oral iron suspension and a test drug suspension, the change of color in the mixture was observed macroscopically and graded as 0 to 3, with a marked color change judged as grade 3 and no color change as grade 0. Screening of 14 test drugs commonly used orally was carried out. When using sodium ferrous citrate preparations as oral iron, 5 were classified as grade 3, 2 as grade 2, 4 as grade 1, and 3 as grade 0, respectively. To verify usefulness of the method, the interactions suggested by screening were pharmacokinetically assessed by measuring serum concentrations of the drug in mice. When a levodopa or droxidopa preparation, judged as grade 3 in screening, was concomitantly administered with an iron preparation, a significant reduction in bioavailability of the test drug was observed, indicating possible drug interaction between the test drug and oral iron. Combined administration of an acetaminophen preparation, judged as grade 1, and oral iron preparation showed no influence on the bioavailability of the test drug, implying no detectable interactions between them. In conclusion, the simple method devised in the present study is useful for precognition of drug interactions between oral iron preparations and phenolic hydroxyl group-containing drugs, and the drugs with a higher grade in screening may induce drug interactions with oral iron.

Acetaminophen↗
PubMed2002

[Human striatal D-neurons and their significance].

It has recently been reported that the human striatum, especially its ventral part, the nucleus accumbens, contains numerous neurons immunoreactive for aromatic L-amino acid decarboxylase (AADC; the second-step monoamine synthesizing enzyme), but not for tyrosine hydroxylase (TH; the first-step catecholamine synthesizing enzyme) or tryptophan hydroxylase (TPH; the first-step serotonin synthesizing enzyme). These AADC (+)/TH(-)/TPH(-) neurons are named D-neurons. AADC is also the rate-limiting synthesizing enzyme of phenylethylamine (PEA). Although the functions of striatal D-neurons are yet unclear, their functions were discussed in the present review based on recent findings in the literature. D-neurons may participate in the manifestation of efficacy of pharmacotherapy for Parkinson's disease by uptaking monoamine precursors, including L-dopa or droxidopa (L-threo-DOPS), and by converting them to dopamine (DA) or noradrenaline (NA), respectively. Because the nucleus accumbens is one of the brain regions involved in the pathogenesis of schizophrenia and drug dependence, D-neurons might be related to the etiology of these mental disorders. It has also been suggested that striatal D-neurons are the pluripotential cells that have compensating functions against aging or degeneration. Further studies should be conducted to elucidate the functions of this unique cell group in the human striatum.

Animals↗
PubMed1997

[Malignant syndrome in multiple system atrophy].

Five of fourteen patients with multiple system atrophy (MSA) experienced a total of eight episodes of malignant syndrome, three episodes in 1, two episodes in 1 patient, and a single episode in each of the other patients. Four patients had extrapyramidal symptoms and required antiparkinson therapy, including dopaminergic agonists. Five episodes occurred in the summer season. Two were caused by decreased or irregular doses of antiparkinson drugs, one by administration of an antidepressant drug, three by complications, and two by elevation of body temperature of environmental origin. A patient without parkinsonism became febrile after administration of droxidopa, which may be a central pyrogenic substance that acts via the noradrenergic system. Administration of dopaminergic drugs and dantrolene sodium was followed by recovery in four episodes in three patients. One patient manifested dysautonomia after recovery from the malignant syndrome. Another patient with high serum creatine kinase levels and myoglobinuria developed renal failure requiring hemodialysis. Another patient died of DIC. Besides withdrawal of dopaminergic agents, which alter monoaminergic neuron activity, stress to the body and heating by a variety of factors tend to trigger the malignant syndrome in MSA.

Adult↗
PubMed1994

A radiological analysis of heart sympathetic functions with meta-[123I]iodobenzylguanidine in neurological patients with autonomic failure.

Cardiac scintigraphy with meta-[123I]iodobenzylguanidine (MIBG) is used to assess cardiac sympathetic function. We performed [123I]MIBG scintigraphy in 7 patients with neurological diseases presenting orthostatic hypotension and other autonomic failures (AF), 22 neurological patients without AF, and 9 healthy subjects. Thallium scintigraphy and echocardiography were also performed in all subjects. In this series, patients with any evidence of cardiac dysfunction were excluded. No [123I]MIBG accumulation was observed in all patients with AF, and cardiac defects were noted in 7 patients (5 with Parkinson's disease [PD], 2 with spinocerebellar degenerations [SCD]), and in some patients without AF. In contrast, the distribution of [123I]MIBG was normal in all the healthy subjects. No decrease in [123I]MIBG accumulation was resulted from drug therapy (droxidopa, amezinium and thyrotropin-releasing hormone). In conclusion, reduced accumulation on [123I]MIBG scintigraphy may be due to myocardial beta-adrenoceptor dysfunction or reduced central sympathetic activity of the heart, or both.

3-Iodobenzylguanidine↗
PubMed2004

Significance of human striatal D-neurons: implications in neuropsychiatric functions.

The human striatum, especially its ventral part, the nucleus accumbens (Acc), contains numerous nonmonoaminergic aromatic L-amino acid decarboxylase (AADC) [=dopa decarboxylase (DDC)] neurons (D-neurons). AADC is the second-step synthesizing enzyme for monoamines and is also the rate-limiting enzyme of phenylethylamine (PEA) synthesis. D-neurons may participate in the manifestation of efficacy of pharmacotherapy for Parkinson's disease by taking up monoamine precursors including L-dopa or droxidopa (L-threo-DOPS) and by converting them to dopamine or noradrenaline, respectively. Although previous studies have shown that AADC activity was elevated in the striatum of drug-naive schizophrenia, the number of striatal D-neurons was reduced in autopsy brains of schizophrenia. It is unclear whether or not such reduction of striatal D-neurons implies downregulation. Possible pluripotentiality of D-neurons, including compensatory functions against aging and degeneration, was discussed based on recent published works.

Animals↗
PubMed1999

Tyrosine hydroxylase and aromatic L-amino acid decarboxylase do not coexist in neurons in the human anterior cingulate cortex.

Immunoreactivity for aromatic L-amino acid decarboxylase (AADC), the second step dopamine-synthesizing enzyme, was found immunohistochemically in neurons of the human anterior cingulate cortex (ACC). Most of these neurons were located in layers V and VI and subcortical white matter; a small number were occasionally found in layer III. Double immunohistochemistry for tyrosine hydroxylase (TH: the first step dopamine-synthesizing enzyme) and AADC revealed that no neuronal cell bodies in the ACC were doubly immunostained for TH and AADC, suggesting that these TH-only- or AADC-only-immunoreactive neurons were not dopaminergic. AADC neurons in the human ACC might transform L-DOPA to dopamine, droxidopa to noradrenaline, and/or 5-hydroxytryptophan to serotonin.

Adult↗
PubMed2002

Transport of amino acid-related compounds mediated by L-type amino acid transporter 1 (LAT1): insights into the mechanisms of substrate recognition.

The L-type amino acid transporter 1 (LAT1) is an Na(+)-independent neutral amino acid transporter subserving the amino acid transport system L. Because of its broad substrate selectivity, system L has been proposed to be responsible for the permeation of amino acid-related drugs through the plasma membrane. To understand the mechanisms of substrate recognition, we have examined the LAT1-mediated transport using a Xenopus laevis oocyte expression system. LAT1-mediated [(14)C]phenylalanine uptake was strongly inhibited in a competitive manner by aromatic-amino acid derivatives including L-dopa, alpha-methyldopa, melphalan, triiodothyronine, and thyroxine, whereas phenylalanine methyl ester, N-methyl phenylalanine, dopamine, tyramine, carbidopa, and droxidopa did not inhibit [(14)C]phenylalanine uptake. Gabapentin, a gamma-amino acid, also exerted a competitive inhibition on LAT1-mediated [(14)C]phenylalanine uptake. Although most of the compounds that inhibited LAT1-mediated uptake were able to induce the efflux of [(14)C]phenylalanine preloaded to the oocytes expressing LAT1 through the obligatory exchange mechanism, melphalan, triiodothyronine, and thyroxine did not induce the significant efflux. Based on the experimental and semiempirical computational analyses, it is proposed that, for an aromatic amino acid to be a LAT1 substrate, it must have a free carboxyl and an amino group. The carbonyl oxygen closer to the amino group needs a computed charge of -0.55 approximately -0.56 and must not participate in hydrogen bonding. In addition, the hydrophobic interaction between the substrate side chain and the substrate binding site of LAT1 seems to be crucial for the substrate binding. A substrate, however, becomes a blocker once Connolly accessible areas become large and/or the molecule has a high calculated logP value, such as those for melphalan, triiodothyronine, and thyroxine.

Amino Acids↗
PubMed2001

Orthostatic hypotension in patients with Parkinson's disease: pathophysiology and management.

Orthostatic hypotension is common in elderly patients, and is now considered to be an important prognostic factor for cognitive decline and mortality. In patients with Parkinson's disease, the prevalence of symptomatic orthostatic hypotension may be as high as 20%. Two factors could explain this high prevalence. First, dopaminergic drugs may induce or worsen orthostatic hypotension. Secondly, Parkinson's disease is a cause of primary autonomic failure with an involvement of the peripheral autonomic system as shown by the ubiquitous distribution of Lewy bodies and reduced iobenguane [metaiodobenzylguanidine (MIBG)] cardiac uptake. These pathological and pharmacological characteristics clearly differentiate autonomic failure of Parkinson's disease from multiple system atrophy. If autonomic abnormalities appear to be present from the first stage of the disease, early onset (within the first year) of symptomatic orthostatic hypotension in the course of parkinsonism can be considered as an exclusion criteria for idiopathic Parkinson's disease. No specific clinical trials have evaluated the effects of antihypotensive drugs in patients with Parkinson's disease and thus no specific therapeutic strategy can be recommended. The management of orthostatic hypotension in patients with Parkinson's disease should always start with patient education and nonpharmacological treatment. Drug therapy should be reserved for symptomatic patients who do not get benefit from nonpharmacological management. Among the available drugs, alpha1-adrenergic agonists (mainly midodrine) or plasma volume expanders (mainly fludrocortisone) are the most frequently used. There are also some drugs that are currently investigational such as yohimbine and droxidopa. Other drugs such as desmopressin or octreotide may be of interest in some situations. Domperidone is widely used in patients with parkinsonism with no proven effect on orthostatic hypotension.

Blood Volume↗
PubMed2002

[High dose L-dopa infusion during general anesthesia for gastrectomy in a patient with parkinsonism].

A 68-year-old man with parkinsonism was scheduled for gastrectomy. Levodopa 1400 mg, droxidopa 300 mg and bromocriptine-mesylate 7.5 mg had been administered orally per day to control the symptom before surgery. On the day before surgery, oral medication was stopped and intravenous infusion of levodopa 100 mg.h-1 was started. Without any premedication but with levodopa infusion, anesthesia was induced with thiopental 175 mg and fentanyl 0.05 mg. Tracheal intubation was facilitated with vecuronium 6 mg and an epidural catheter was inserted. Anesthesia was maintained with O2, N2O and sevoflurane, combined with epidural block using mepivacaine. When blood pressure decreased, phenylephrine but not ephedrine was effective to increase blood pressure. Intravenous infusion of levodopa was continued for 19 days with decreasing doses from 8th postoperative day when injection of levodopa into the intestinal tube was started. On the 53rd day, he left the hospital without any complications. Serum concentrations of levodopa during and after surgery were 50 to 100 times higher than the therapeutic levels. However, he developed no complications, which suggests a wide safety range of levodopa. In conclusion, high dose levodopa infusion was effective in controlling the symptoms of Parkinsonism during general anesthesia.

Aged↗
PubMed2002

[Localization of non-monoaminergic aromatic L-amino acid decarboxylase neurons (D-neurons) in the human striatum and their functional significance].

It has recently been reported that the human corpus striatum, especially its ventral part, named as the nucleus accumbens, contains numerous non-monoaminergic aromatic L-amino acid decarboxylase (AADC; the second-step monoamine synthesizing enzyme) neurons (D-neurons). D-neurons are the neurons immunoreactive for AADC but not immunoreactive for dopamine or serotonin. They lack the first-step monoamine synthesizing enzymes, tyrosine hydroxylase and tryptophan hydroxylase. AADC is also the rate-limiting enzyme of phenylethylamine (PEA) synthesis. D-neurons might participate in the manifestation of efficacy of pharmacotherapy for Parkinson's disease by uptaking monoamine precursors including L-dopa or droxidopa (L-threo-DOPS) and by converting them to dopamine or noradrenaline, respectively. As the nucleus accumbens is one of the brain regions that are involved in the pathogenesis of schizophrenia and drug dependence, D-neurons might be related to the etiology of these mental disorders. It has also been suggested that striatal D-neurons are the pluripotential cells that have compensating functions against aging or degeneration.

Aromatic-L-Amino-Acid Decarboxylases↗
PubMed1992

[Parkinson's disease with syncope as a chief complaint induced by prominent postprandial hypotension].

A 77-year-old man developed syncope after meals at the age of 75. He had been treated with anti-Parkinson's drugs such as levodopa for 18 years as a patient with idiopathic Parkinson's disease (PD). The medications had been very effective to his parkinsonism. Ambulatory blood pressure was recorded every 20 minutes throughout one day by indirect measurement using a Colin medical instrument monitor (ABPM-630). The subsequent data disclosed that postprandial hypotension (PPH) was associated with the frequent after-meal syncope. It was also found that oral ingestion of a solution containing 50 grams of glucose caused a marked and prolonged hypotension during the resting supine position. Plasma norepinephrine failed to show any increment. Plasma vasopressin slightly increased while pulse rate, plasma renin activity, osmolality, and hematocrit did not change despite the production of severe hypotension of a relative acute onset. Signs of glucose intolerance and hyperinsulinemic response were observed. Indications of systemic autonomic nervous dysfunctions were revealed in various autonomic nervous function tests. Physical treatment combined with medication such as droxidopa, midodrine and especially caffeine and fludrocortisone proved to be effective on PPH. The authors confirmed the existence of PD with symptomatic PPH. In addition, we considered this present case as an example of "progressive autonomic failure with PD" (Bannister, 1988).

Aged↗
PubMed1994

[A case of progressive supranuclear palsy showing improvement of rigidity, nuchal dystonia and autonomic failure with trazodone].

A 63-year-old man was admitted to the hospital with a 1,5-year history of progressive dementia, supranuclear ophthalmoplegia, pseudobulbar palsy, rigidity and dystonia in the neck and the upper trunk. Magnetic resonance imagings showed severe atrophy of the frontal lobe and the brainstem. He was diagnosed as having progressive supranuclear palsy (PSP). Rigidity, nuchal dystonia, frequent micturition, and profuse sweating ameliorated after trazodone administration. Furthermore, additional administration of L-dopa and droxidopa improved his pseudobulbar palsy, akinesia, and lack of initiative. Single photon emission tomography using IMP after medication showed increased IMP-uptake in the frontal areas and the basal ganglia compared with that before medication. This patient illustrates a substantial role of impairments in the serotonin system in the production of some PSP symptoms.

Autonomic Nervous System Diseases↗