Effects of α-methyl-para-tyrosine (AMPT) in drug-free depressed patients

Helen L. Miller, Pedro L. Delgado, Ronald M. Salomon, George R. Heninger, Dennis S. Charney

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Original languageEnglish
Pages (from-to)151-157
Number of pages7
JournalNeuropsychopharmacology
Volume14
Issue number3
DOIs
StatePublished - Mar 1996
Externally publishedYes

Fingerprint

Tyrosine
Diphenhydramine
Depression
Pharmaceutical Preparations
Homovanillic Acid
Norepinephrine
Methoxyhydroxyphenylglycol
Tyrosine 3-Monooxygenase
Visual Analog Scale
Tryptophan
Diagnostic and Statistical Manual of Mental Disorders
Catecholamines
Dopamine
Emotions
Placebos
Brain

ASJC Scopus subject areas

  • Pharmacology

Cite this

Miller, H. L., Delgado, P. L., Salomon, R. M., Heninger, G. R., & Charney, D. S. (1996). Effects of α-methyl-para-tyrosine (AMPT) in drug-free depressed patients. Neuropsychopharmacology, 14(3), 151-157. https://doi.org/10.1016/0893-133X(95)00072-L

Effects of α-methyl-para-tyrosine (AMPT) in drug-free depressed patients. / Miller, Helen L.; Delgado, Pedro L.; Salomon, Ronald M.; Heninger, George R.; Charney, Dennis S.

In: Neuropsychopharmacology, Vol. 14, No. 3, 03.1996, p. 151-157.

Research output: Contribution to journalArticle

Miller, HL, Delgado, PL, Salomon, RM, Heninger, GR & Charney, DS 1996, 'Effects of α-methyl-para-tyrosine (AMPT) in drug-free depressed patients', Neuropsychopharmacology, vol. 14, no. 3, pp. 151-157. https://doi.org/10.1016/0893-133X(95)00072-L
Miller, Helen L. ; Delgado, Pedro L. ; Salomon, Ronald M. ; Heninger, George R. ; Charney, Dennis S. / Effects of α-methyl-para-tyrosine (AMPT) in drug-free depressed patients. In: Neuropsychopharmacology. 1996 ; Vol. 14, No. 3. pp. 151-157.
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title = "Effects of α-methyl-para-tyrosine (AMPT) in drug-free depressed patients",
abstract = "A variety of biologic studies have demonstrated abnormal regulation of the norepinephrine (NE) system in patients with major depression, suggesting a role for NE in the etiology of depression. Brain NE and dopamine levels can be rapidly reduced by blocking synthesis with the tyrosine hydroxylase inhibitor α-methyl-para-tyrosine (AMPT). In the current investigation, AMPT was administered to drug-free depressed patients to evaluate the effect on mood of diminished catecholamine levels. Seventeen drug-free patients meeting DSM-III-R criteria for major depressive episode were tested with AMPT and an active placebo control, diphenhydramine. Testing was accomplished in a double-blind, crossover fashion, with random assignment to test conditions. Each test included baseline evaluation, 2 days with administration of either AMPT or diphenhydramine, and a follow-up day. Diphenhydramine was used as an active control because of the significant sedation associated with AMPT. Behavioral ratings, including visual analogue scales for a variety of feeling states, the Hamilton Depression Rating Scale (HDRS), and plasma for 3-methoxy-4-hydroxyphenelethyleneglycol (MPHG) and homovanillic acid (HVA) levels, were obtained. AMPT significantly reduced plasma HVA by 70{\%} and MHPG by 50{\%}, but it had no significant effects on the DHRS. AMPT also significantly increased visual analogue ratings of 'tired' and decreased ratings of 'energetic'. Diphenhydramine significantly decreased HDRS scores, but the change was small and was not clinically apparent. The lack of AMPT effects on depressed mood, in conjunction with a prior report that large reductions in plasma tryptophan do not systematically alter depressed mood, indicate that monoamine deficiency by itself is insufficient explanation of the cause of depression. The role of the noradrenergic system needs to be considered in relationship to the many other neurobiologic factors that could be involved in the pathophysiology of depression.",
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AB - A variety of biologic studies have demonstrated abnormal regulation of the norepinephrine (NE) system in patients with major depression, suggesting a role for NE in the etiology of depression. Brain NE and dopamine levels can be rapidly reduced by blocking synthesis with the tyrosine hydroxylase inhibitor α-methyl-para-tyrosine (AMPT). In the current investigation, AMPT was administered to drug-free depressed patients to evaluate the effect on mood of diminished catecholamine levels. Seventeen drug-free patients meeting DSM-III-R criteria for major depressive episode were tested with AMPT and an active placebo control, diphenhydramine. Testing was accomplished in a double-blind, crossover fashion, with random assignment to test conditions. Each test included baseline evaluation, 2 days with administration of either AMPT or diphenhydramine, and a follow-up day. Diphenhydramine was used as an active control because of the significant sedation associated with AMPT. Behavioral ratings, including visual analogue scales for a variety of feeling states, the Hamilton Depression Rating Scale (HDRS), and plasma for 3-methoxy-4-hydroxyphenelethyleneglycol (MPHG) and homovanillic acid (HVA) levels, were obtained. AMPT significantly reduced plasma HVA by 70% and MHPG by 50%, but it had no significant effects on the DHRS. AMPT also significantly increased visual analogue ratings of 'tired' and decreased ratings of 'energetic'. Diphenhydramine significantly decreased HDRS scores, but the change was small and was not clinically apparent. The lack of AMPT effects on depressed mood, in conjunction with a prior report that large reductions in plasma tryptophan do not systematically alter depressed mood, indicate that monoamine deficiency by itself is insufficient explanation of the cause of depression. The role of the noradrenergic system needs to be considered in relationship to the many other neurobiologic factors that could be involved in the pathophysiology of depression.

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