関: alpha-methyltyrosine、metyrosine

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/01/17 13:45:02」(JST)

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Metirosine (α-Methyltyrosine, Metyrosine, AMPT) is an antihypertensive drug. It inhibits the enzyme tyrosine hydroxylase and, therefore, catecholamine synthesis, which, as a consequence, depletes the levels of the catecholamines dopamine, adrenaline and noradrenaline in the body.

Clinical use

Metirosine has been used in the treatment of pheochromocytoma.^[1] It is contra-indicated for the treatment of essential hypertension.

However it is now rarely used in medicine, and its main use is in scientific research, to investigate the effects of catecholamine depletion on behaviour.^[2]

Chemistry

Metyrosine, (−)α-methyltyrosine, is synthesized in a few different ways, the simplest of which is the synthesis from 4-methoxyphenylacetone, which is reacted with potassium cyanide in the presence of ammonium carbonate to give the hydantoin. Treating this with hydrogen iodide removes the methyl-protecting group on the phenyl hydroxyl group and the product is hydrolyzed by barium hydroxide into a racemic mixture of α-methyl-D,L-tyrosine, from which the desired L-isomer is isolated.

Stein, G. A.; Bronner, H. A.; Pfister, K. (1955). Journal of the American Chemical Society 77 (3): 700. doi:10.1021/ja01608a046. edit
K. Potts, J. Chem. Soc., 1632 (1955).
Saari, W. S. (1967). "Reaction of nitro anions with N,N-dimethyl-p-hydroxybenzylamine. A new synthesis of alpha-methyltyrosine". Journal of Organic Chemistry 32 (12): 4074–4076. doi:10.1021/jo01287a087. PMID 5622474. edit
G.A. Stein, I.K. Pfister, U.S. Patent 2,868,818 (1959).

References

^ Green KN, Larsson SK, Beevers DG, Bevan PG, Hayes B (August 1982). "Alpha-methyltyrosine in the management of phaeochromocytoma". Thorax 37 (8): 632–3. doi:10.1136/thx.37.8.632. PMC 459390. PMID 7179194. //www.ncbi.nlm.nih.gov/pmc/articles/PMC459390/.
^ O'Leary OF, Bechtholt AJ, Crowley JJ, Hill TE, Page ME, Lucki I. Depletion of serotonin and catecholamines block the acute behavioral response to different classes of antidepressant drugs in the mouse tail suspension test. Psychopharmacology (Berlin). 2007 Jun;192(3):357-71. PMID 17318507

English Journal

New PET radiopharmaceuticals beyond FDG for brain tumor imaging.

Guliás B, Halldin C.SourcePsychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden - balazs.gulyas@ki.se.
The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of Radiopharmaceutical Chemistry and Biology.Q J Nucl Med Mol Imaging.2012 Apr;56(2):173-90.
Brain tumors have a relatively high incidence (>14/100000 people/year) and represent a major cause of death in the population. The direct and indirect costs of brain tumors are high in the developed countries (5.2 bn EUR/year in the EU; 4.46 bn USD/year in the US). A combination of recent advance
PMID 22617239

Safety and tolerability of magnetic resonance imaging-guided convection-enhanced delivery of AAV2-hAADC with a novel delivery platform in nonhuman primate striatum.

San Sebastian W, Richardson RM, Kells AP, Lamarre C, Bringas J, Pivirotto P, Salegio EA, Dearmond SJ, Forsayeth J, Bankiewicz KS.SourceDepartment of Neurological Surgery, University of California San Francisco , San Francisco, CA 94103, USA.
Human gene therapy.Hum Gene Ther.2012 Feb;23(2):210-7. Epub 2012 Jan 26.
Degeneration of nigrostriatal neurons in Parkinson's disease (PD) causes progressive loss of aromatic l-amino acid decarboxylase (AADC), the enzyme that converts levodopa (l-DOPA) into dopamine in the striatum. Because loss of this enzyme appears to be a major driver of progressive impairment of res
PMID 22017504

「metyrosine」

Metyrosine
Systematic (IUPAC) name
	(2S)-2-amino- 3-(4-hydroxyphenyl)- 2-methylpropanoic acid
Clinical data
Trade names	Demser
AHFS/Drugs.com	Consumer Drug Information
Pregnancy cat.	?
Legal status	?
Pharmacokinetic data
Half-life	3.4–3.7 hours
Identifiers
CAS number	672-87-7
ATC code	C02KB01
PubChem	CID 10123
DrugBank	DB00765
ChemSpider	390103
UNII	DOQ0J0TPF7
KEGG	D00762
ChEMBL	CHEMBL1200862
Chemical data
Formula	C10H13NO3
Mol. mass	195.215 g/mol
	SMILES O=C(O)[C@@](N)(Cc1ccc(O)cc1)C;
	InChI InChI=1S/C10H13NO3/c1-10(11,9(13)14)6-7-2-4-8(12)5-3-7/h2-5,12H,6,11H2,1H3,(H,13,14)/t10-/m0/s1 ; Key:NHTGHBARYWONDQ-JTQLQIEISA-N ;
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