Inhibition of presynaptic catecholamine synthesis with alpha-methyl-para-tyrosine attenuates nocturnal melatonin secretion in humans.
The catecholamine dopamine (D) is involved in the regulation of LH and PRL secretion, whereas a dysregulated noradrenergic system may contribute significantly to symptoms encountered in affective disorders. This explains the attraction of using alpha-methyl-para-tyrosine (AMPT) in neuroendocrine and psychiatric research, as it inhibits both neurotransmitters. PRL has been used as a marker of the effectiveness of AMPT in blocking D function, but no good marker for the effectiveness of AMPT in blocking norepinephrine (NE) is available. The purpose of this study was to determine whether melatonin (M) might serve as such a marker, as its production and secretion are regulated by NE. Seven subjects were given either AMPT or promethazine, which does not alter M secretion, in a randomized, double blind fashion, and 24-h M secretion was studied. Two-way analysis of variance revealed a significant difference in M secretion (F = 13.2; df = 17,102; P = 0.0013), with the following time points being different: 22, 23, 24, 1, 2, 3, 4, 5, and 6 h. Also, 24-h urinary 6-sulfatoxymelatonin excretion correlated highly with 24-h M secretion, expressed as the area under the curve in the AMPT experiment (r = 0.93; P = 0.002), which indicates that AMPT does not alter the metabolism of M. These results demonstrate for the first time that AMPT significantly attenuates nocturnal M secretion. It is concluded that M is a good marker for characterizing the effectiveness of AMPT in inhibiting sympathetic NE activity.
Zimmermann
R C
RC
Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota 55905.
Krahn
L
L
Klee
G
G
Delgado
P
P
Ory
S J
SJ
Lin
S C
SC
D000328:Adult; D015415:Biomarkers; D002395:Catecholamines / Q000037:antagonists & inhibitors*; D002940:Circadian Rhythm; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008550:Melatonin / Q000378:metabolism*; D008781:Methyltyrosines / Q000494:pharmacology*; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D017729:Presynaptic Terminals / Q000378:metabolism*; D013997:Time Factors; D019805:alpha-Methyltyrosine
D015415:Biomarkers; D002395:Catecholamines; D008781:Methyltyrosines; D019805:alpha-Methyltyrosine; D008550:Melatonin; D009638:Norepinephrine