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Revision as of 18:54, 14 November 2011 editCheMoBot (talk | contribs)Bots141,565 edits Updating {{drugbox}} (no changed fields - added verified revid - updated 'DrugBank_Ref', 'ChEMBL_Ref', 'ChEBI_Ref', 'KEGG_Ref', 'CAS_number_Ref') per Chem/Drugbox validation (report [[Misplaced Pages talk:WikiProject_Pharmacology|errors...← Previous edit Revision as of 07:40, 13 May 2012 edit undoAcamp guzman (talk | contribs)9 editsm Added information regarding Pharmacokinetics and Pharmacodynamics of AMPT as well as medical use and side-effects of the drug.Next edit →
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| StdInChIKey = NHTGHBARYWONDQ-UHFFFAOYSA-N | StdInChIKey = NHTGHBARYWONDQ-UHFFFAOYSA-N
}} }}
'''Alpha-methyl-p-tyrosine (AMPT)''' is a ] enzyme inhibitor. Alpha-methyl-p-tyrosine (AMPT) is a non-endogenous drug involved in the catecholamine biosynthetic pathway. <ref name="nestler">,additional text.</ref> AMPT inhibits tyrosine hydroxylase whose enzymatic activity is regulated through the phosphorylation of different serine residue regulatory domain sites.<ref name="nestler" /> Catecholamine biosynthesis starts with dietary tyrosine, which is hydroxylated by the enzyme tyrosine hydroxylase. It is hypothesized that AMPT competes with tyrosine at the tyrosine-binding site, causing inhibition of tyrosine hydroxylase.<ref name="ankenman">, additional text.</ref>
⚫ '''Alpha-methyl-p-tyrosine (AMPT)''' is a ] enzyme inhibitor. It has been used in the treatment of ].<ref name="pmid17308229">{{cite journal |author=Ankenman R, Salvatore MF |title=Low dose alpha-methyl-para-tyrosine (AMPT) in the treatment of dystonia and dyskinesia |journal=J Neuropsychiatry Clin Neurosci |volume=19 |issue=1 |pages=65–69 |year=2007 |pmid=17308229 |doi=10.1176/appi.neuropsych.19.1.65 |url=}}</ref> It has been demonstrated to inhibit the production of melanin.<ref></ref>

⚫ It has been used in the treatment of ].<ref name=ankenman /> It has been demonstrated to inhibit the production of melanin.<ref></ref>

==Pharmacology==
'''''Effect on Catecholamine Biosynthesis'''''

AMPT inhibits catecholamine biosynthesis at the first step—the hydroxylation of tyrosine.<ref name="brogden">, additional text.</ref> Reduction in catecholamines and their metabolites (normetanephrine, metanephrine, and 4-hydroxy-3-methoxymandelic acid) result from the inhibition of tyrosine using AMPT.<ref name="brogden" /> AMPT doses of 600 to 4,000mg per day cause a 20 to 79 percent reduction in total catecholamines in Pheochromocytoma patients.<ref name="brogden" /> Increase in dosage increases the magnitude of catecholamine synthesis inhibition.<ref name="brogden" /> This increasing inhibitory effect is seen in dosages up to 1500mg per day; at higher doses the inhibitory effect of AMPT decreases.<ref name="brogden" /> Maximum effect of orally administered AMPT occurs 48 to 72 hours after administration of the drug.<ref name="engelman 1968">, additional text.</ref> Catecholamine production levels return to normal 72 to 96 hours after administration of the drug ceases.<ref name="engelman">, additional text.</ref> Dosages as low as 300mg per day have been found to have an affect on catecholamine production which can be measured through urinary excretion analysis and cerebral spinal fluid assays.<ref name="brogden" />
AMPT is successful at inhibiting catecholamine production in humans whether the rate of synthesis is high, as in Pheochromocytoma, or normal as in patients with hypertension.<ref name="engelman 1968" />

'''''Effect on Blood Pressure'''''

Pheochromocytoma patients exhibited a drop in blood pressure when taking AMPT.<ref name=engelman /> AMPT had no effect in patients with Hypertension (high blood pressure).<ref name=engelman />

==Pharmacokinetics==
'''''Absorption'''''

'''''Half-life'''''


'''''Elimination'''''


==Medical Use==
'''''Pheochromocytoma'''''

'''''Drug Interactions'''''
''Psychosis''

'''''Cocaine and Methamphetamines'''''

'''''Dystonia and Dyskinesia'''''




==Side-effects== ==Side-effects==

AMPT administration leads to a transient exacerbation of depressive symptoms in patients that have responded to catecholaminergic ]. The ] changes induced by AMPT may be mediated by decreases in ], while changes in selective attention and motivation may be mediated by ].


Prolonged administration can have an impact upon the ].<ref name="pmid11390253">{{cite journal |author=Zimmermann RC, Krahn LE, Klee GG, Ditkoff EC, Ory SJ, Sauer MV |title=Prolonged inhibition of presynaptic catecholamine synthesis with alpha-methyl-para-tyrosine attenuates the circadian rhythm of human TSH secretion |journal=J. Soc. Gynecol. Investig. |volume=8 |issue=3 |pages=174–178 |year=2001 |pmid=11390253 |doi= 10.1016/S1071-5576(01)00104-6|url=http://linkinghub.elsevier.com/retrieve/pii/S1071557601001046}}</ref> Prolonged administration can have an impact upon the ].<ref name="pmid11390253">{{cite journal |author=Zimmermann RC, Krahn LE, Klee GG, Ditkoff EC, Ory SJ, Sauer MV |title=Prolonged inhibition of presynaptic catecholamine synthesis with alpha-methyl-para-tyrosine attenuates the circadian rhythm of human TSH secretion |journal=J. Soc. Gynecol. Investig. |volume=8 |issue=3 |pages=174–178 |year=2001 |pmid=11390253 |doi= 10.1016/S1071-5576(01)00104-6|url=http://linkinghub.elsevier.com/retrieve/pii/S1071557601001046}}</ref>
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==Mechanism== ==Mechanism==
As a ] of ], it prevents the conversion of ] to ], the precursor to ]. This results in lowered systematic ] (], ] and ]) levels. As a ] of ], it prevents the conversion of ] to ], the precursor to ]. This results in lowered systematic ] (], ] and ]) levels.

]




==References== ==References==

Revision as of 07:40, 13 May 2012

Pharmaceutical compound
Α-Methyl-p-tyrosine
Identifiers
IUPAC name
  • 2-amino-3-(4-hydroxyphenyl)-2-methylpropanoic acid
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard100.010.477 Edit this at Wikidata
Chemical and physical data
FormulaC10H13NO3
Molar mass195.215 g/mol g·mol
3D model (JSmol)
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)
  • Key:NHTGHBARYWONDQ-UHFFFAOYSA-N
  (verify)

Alpha-methyl-p-tyrosine (AMPT) is a tyrosine hydroxylase enzyme inhibitor. Alpha-methyl-p-tyrosine (AMPT) is a non-endogenous drug involved in the catecholamine biosynthetic pathway. AMPT inhibits tyrosine hydroxylase whose enzymatic activity is regulated through the phosphorylation of different serine residue regulatory domain sites. Catecholamine biosynthesis starts with dietary tyrosine, which is hydroxylated by the enzyme tyrosine hydroxylase. It is hypothesized that AMPT competes with tyrosine at the tyrosine-binding site, causing inhibition of tyrosine hydroxylase.

It has been used in the treatment of pheochromocytoma. It has been demonstrated to inhibit the production of melanin.

Pharmacology

Effect on Catecholamine Biosynthesis

AMPT inhibits catecholamine biosynthesis at the first step—the hydroxylation of tyrosine. Reduction in catecholamines and their metabolites (normetanephrine, metanephrine, and 4-hydroxy-3-methoxymandelic acid) result from the inhibition of tyrosine using AMPT. AMPT doses of 600 to 4,000mg per day cause a 20 to 79 percent reduction in total catecholamines in Pheochromocytoma patients. Increase in dosage increases the magnitude of catecholamine synthesis inhibition. This increasing inhibitory effect is seen in dosages up to 1500mg per day; at higher doses the inhibitory effect of AMPT decreases. Maximum effect of orally administered AMPT occurs 48 to 72 hours after administration of the drug. Catecholamine production levels return to normal 72 to 96 hours after administration of the drug ceases. Dosages as low as 300mg per day have been found to have an affect on catecholamine production which can be measured through urinary excretion analysis and cerebral spinal fluid assays. AMPT is successful at inhibiting catecholamine production in humans whether the rate of synthesis is high, as in Pheochromocytoma, or normal as in patients with hypertension.


Effect on Blood Pressure

Pheochromocytoma patients exhibited a drop in blood pressure when taking AMPT. AMPT had no effect in patients with Hypertension (high blood pressure).

Pharmacokinetics

Absorption

Half-life


Elimination


Medical Use

Pheochromocytoma


Drug Interactions Psychosis

Cocaine and Methamphetamines

Dystonia and Dyskinesia


Side-effects

Prolonged administration can have an impact upon the circadian rhythm.

Mechanism

As a competitive inhibitor of tyrosine hydroxylase, it prevents the conversion of tyrosine to L-DOPA, the precursor to dopamine. This results in lowered systematic catecholamine (dopamine, epinephrine and norepinephrine) levels.

Biosynthesis of dopamine:Dopamine, norepinephrine, and epinephrine are all synthesized through a multistep processing of tyrosine. Tyrosine is a highly concentrated amino acid in catecholaminergic neurons


References

  1. ^ ,additional text.
  2. ^ , additional text.
  3. Use of α-methyl-p-tyrosine to inhibit melanin production in iris melanocytes
  4. ^ , additional text.
  5. ^ , additional text.
  6. ^ , additional text.
  7. Zimmermann RC, Krahn LE, Klee GG, Ditkoff EC, Ory SJ, Sauer MV (2001). "Prolonged inhibition of presynaptic catecholamine synthesis with alpha-methyl-para-tyrosine attenuates the circadian rhythm of human TSH secretion". J. Soc. Gynecol. Investig. 8 (3): 174–178. doi:10.1016/S1071-5576(01)00104-6. PMID 11390253.{{cite journal}}: CS1 maint: multiple names: authors list (link)

External links

  • and A Clinical Trial
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