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 contri bute significantly to symptoms encountered in affective disorders. Thi s explains the attraction of using cu-methyl-para-tyrosine (AMPT) in n euroendocrine and psychiatric research, as it inhibits both neurotrans mitters. 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 stu dy 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 after M secreti on, in a randomized, double blind fashion, and 24-h M: secretion was s tudied. Two-way analysis of variance revealed a significant difference in M secretion (F = 13.2; df = 17,102; P = 0.0013), with the followin g time points being different: 22, 23, 24, 1, 2, 3, 4, 5, and 6 h. Als o, 24-h urinary 6-sulfatoxymelatonin excretion correlated highly with 24-h M secretion, expressed as the area under the curve in the AMPT ex periment (r = 0.93; P = 0.002), which indicates that AMPT does not alt er the metabolism of M. These results demonstrate for the first time t hat AMPT significantly attenuates nocturnal M secretion. It is conclud ed that M is a good marker for characterizing the effectiveness of AMP T in inhibiting sympathetic NE activity.