DEMSER (Metyrosine) inhibits tyrosine hydroxylase, which catalyzes the first transformation in catecholamine biosynthesis, i.e., the conversion of tyrosine to dihydroxyphenylalanine (DOPA).
DEMSER is indicated in the treatment of patients with pheochromocytoma for:
Preoperative preparation of patients for surgery
Management of patients when surgery is contraindicated
Chronic treatment of patients with malignant pheochromocytoma.
DEMSER is not recommended for the control of essential hypertension.
Published Studies Related to Demser (Metyrosine)
Metyrosine in psychosis associated with 22q11.2 deletion syndrome: case report. [2007.02]
This report describes the use of metyrosine (Demser) in an adolescent male with psychosis associated with the 22q11.2 deletion syndrome (velocardiofacial syndrome; VCFS), diagnosed by fluorescence in situ hybridization (FISH). He presented with multiple features of 22q11.2 deletion syndrome, including ventricular septal defect, palatal abnormalities, speech and motor delays, attention deficits, mood lability, and psychosis...
Metyrosine and pheochromocytoma. [1997.04.28]
BACKGROUND: Severe hemodynamic instability may occur during surgery for removal of pheochromocytoma, unless there is preoperative pharmacological treatment. OBJECTIVE: To evaluate the effects of metyrosine (alpha-methyl-p-tyrosine), a catecholamine synthesis inhibitor, and alpha-blockade with prazosin or phenoxybenzamine on cardiovascular morbidity during surgery for pheochromocytoma... CONCLUSIONS: The combination of alpha-metyrosine and alpha-blockade results in better blood pressure control and less need for use of antihypertensive medication or pressors during surgery, compared with the classical method of single-agent adrenergic blockade. Preoperative treatment with metyrosine along with an alpha-blocker is a useful strategy for decreasing the surgical morbidity in patients with pheochromocytoma and assumes greater importance as long as the availability of phentolamine for intraoperative use is a problem.
Surgical management of pheochromocytoma with the use of metyrosine. [1990.11]
Despite recommended preoperative preparation with alpha-adrenergic blockers, severe hemodynamic instability may occur during operations to resect pheochromocytoma. We combined the alpha-blocker phenoxybenzamine with the tyrosine hydroxylase inhibitor metyrosine in an attempt to better manage the hypertension of patients with pheochromocytoma undergoing surgical resection.
Clinical Trials Related to Demser (Metyrosine)
Metyrosine (DemserŪ) for the Treatment of Psychotic Disorders in Patients With Velocardiofacial Syndrome [Recruiting]
This is an exploratory clinical investigation. The objectives of this study are to evaluate
the safety, steady-state pharmacokinetics, and efficacy of metyrosine (DemserŪ) for the
treatment of psychosis in patients with velocardiofacial syndrome (VCFS).
Treatment of Orthostatic Hypotension [Recruiting]
The purpose of this study is to try different medications in patients with low blood
pressure and other problems with their involuntary (autonomic) nervous system. The
pharmacological trials in this study will perhaps lead to more effective treatment. This
study consists of single dose trials, dose selection trials, 5-day trials and chronic
(approximately 2 months) trials.
PET Imaging of Dopamine in Healthy Study Participants [Completed]
The purpose of this study is to measure molecules on or in cells that interact with a
chemical in the nervous system, called dopamine. Investigators will obtain two kinds of
images of the brain-a position emission tomography (PET) scan and a magnetic resonance
imaging (MRI) scan.
Thirty-eight participants aged 18 to 45 will be enrolled in this study. They must have no
history of medical or psychiatric illness, including substance abuse. Participants will have
four appointments at NIH. On the first visit, they will undergo a physical exam, a medical
history, and lab tests. The second and third visits will involve PET scans and the fourth
visit will involve an MRI scan.
Participants will be compensated up to $430 for their involvement in this study.
131MIBG to Treat Malignant Pheochromocytoma [Recruiting]
This study will evaluate the effectiveness of 131MIBG in treating malignant pheochromocytoma
and whether sensitization medications improve the response to treatment. Pheochromocytoma is
a rare type of tumor that usually occurs in the adrenal glands. The tumor cells release
chemicals like adrenaline that can cause large increases in blood pressure and pulse rate,
with serious health consequences. Tumor in the adrenal glands usually can be removed
surgically, but if the pheochromocytoma is malignant-i. e., has spread to many sites in the
body-or is located in places where surgery is difficult or impossible, no satisfactory
treatment is available. 131MIBG is a combination of an adrenaline-like chemical and a
radioactive form of iodine. The 131MIBG attaches to the tumor cells and the high
concentration of radioactive iodine kills them. Previous studies using 131MIBG to treat
pheochromocytoma had a 36% response rate in terms of complete or partial improvement. This
study will examine whether adding other sensitization medications to the 131MIBG treatment
regimen will enhance its effectiveness in reducing the size and number of tumors.
Patients 18 years of age and older with malignant or inoperable pheochromocytoma may be
eligible for this 18-month study. Candidates will be screened with various tests and
procedures, which may include a medical history, physical examination, blood and urine tests,
lung function studies, electrocardiogram, echocardiogram, computed tomography (CT), magnetic
resonance imaging (MRI), positron emission tomography (PET), and bone scans and other scans
using radioactive MIBG and octreotide.
Participants will be randomly assigned to one of two treatment groups: 1) 131MIBG plus
sensitization medications, or 2) 131MIBG alone. All patients will be hospitalized 3 to 5 days
for each 131MIBG treatment. The drug will be infused through a vein (intravenously, or I. V.)
over 10 to 30 minutes. Patients will receive up to 3 treatments, separated by at least 3
months. All patients will also take potassium to protect the thyroid gland from radioactive
iodine generated by the 131MIBG. The potassium is taken twice a day for 30 days, beginning
the day before the 131MIBG treatment. Patients in the sensitization group will receive the
following additional drugs for sensitization: methylprednisolone, intravenously a few minutes
before 131MIBG treatment; Roaccutan, by mouth (capsules) twice a day for 6 weeks before
treatment; Demser, by mouth 3 times a week for 1 week before treatment, and Carbidopa, by
mouth every 6 hours for 4 days before treatment.
After each treatment, patients will have a clinical evaluation and periodic blood tests to
check for adverse side effects of radiotherapy. Follow-up visits at NIH will be scheduled at
12 and 18 months after the first 131MIBG treatment for clinical, laboratory and imaging
tests. Patients who had tumors in the lungs before treatment will have lung function tests 1,
3, and 6 months after each treatment. CT, MRI 131MIBG, and PET scanning will be done 1 week
before each treatment.
Patients who have tumors that have grown by more than 25% and none that have shrunk by more
than 50% or who have developed one or more new tumors while on 131MIBG treatment will be
taken off the study.
Study of Memantine for Gait Disorders And Attention Deficit In Parkinson's Disease [Recruiting]
Along with cognitive and psychobehavioural disorders, gait disorders represent a major
problem in the treatment of advanced Parkinson's disease (PD). PD can be considered to be a
hyperglutamatergic disease because dopaminergic depletion induces hyperactivity of the
subthalamic nucleus (STN) and the internal pallidum (GPi), with glutamatergic hyperactivity
of the STN's efferent pathway, i. e., the subthalamopallidal, subthalamonigral and
subthalamo-entopeduncular pathways (projecting to the pedunculopontine nucleus (PPN)).
Excess glutamate in the PPN has also been observed in the 6-OHDA rat model of PD. Reduction
of this glutamatergic hyperactivity within the PPN via the systemic or intra-peduncular
administration of glutamate antagonists improves akinesia in drug-induced murine and primate
models of PD, via the NMDA and AMPA receptors. High doses of memantine (10 mg/kg) improve
locomotion in reserpine- and alpha-methyl-p-tyrosine-treated rats. In humans, the PPN may
play a key role in gait, posture control, axial rigidity and attention. It is also involved
in the gating of sensory information involved in the startle reflex, which can be studied
via prepulse inhibition (PPI) of the blink reflex. At present, two uncompetitive NMDA
receptor antagonists are approved for use in humans: amantadine and memantine. Reviews of
the recent literature on these drugs have identified no published studies specifically on
severe gait and attention disorders in PD. Memantine is a partial blocker of open NMDA
channels. The value of memantine relates to the fact that it decreases excessive
glutamatergic transmission by lowering the synaptic noise due to excessive activation of
NMDA receptors. In this double-blind study, the investigators shall seek to demonstrate the
presence or absence of an effect of memantine on gait and attention disorders. In order to
study the interaction between glutamatergic hyperactivity and the dopaminergic system, the
investigators shall study the phenomena both in the absence of L-dopa and following acute
administration of the latter. Twenty eight volunteer, non-demented, late-stage PD patients
displaying severe gait disorders will receive memantine (20 mg/day) or placebo for 3 months.
The investigators expect to see a reduction in gait and attention disorders, together with
an improvement in the blink reflex with PPI under memantine. This pilot study could
subsequently be turned into a double-blind, placebo-controlled multicentre study.
Page last updated: 2007-06-01