Comparison of the effects of acute fluvoxamine and desipramine administration on melatonin and cortisol production in humans.

Abstract

1. Acute administration of the specific serotonin uptake inhibitor, fluvoxamine (100 mg at 16.00 h), markedly increased nocturnal plasma melatonin concentrations, with high levels extending into the morning hours. 2. Acute administration of the noradrenaline uptake inhibitor, desipramine (DMI) (100 mg at 16.00 h), increased evening plasma melatonin concentrations. 3. Both drug treatments increased the duration of melatonin secretion, fluvoxamine significantly delaying the offset time and DMI significantly advancing the onset time. 4. The stimulatory effect of DMI on plasma melatonin was mirrored by increased urinary 6‐sulphatoxymelatonin (aMT6s) excretion. 5. On the contrary, there was no correlation between plasma melatonin and urinary aMT6s concentrations following fluvoxamine treatment, suggesting that fluvoxamine may inhibit the metabolism of melatonin. 6. Treatment with DMI increased plasma cortisol concentrations in the evening and early morning, treatment with fluvoxamine increased plasma cortisol at 03.00 h, 10.00 h and 11.00 h. 7. The drug treatments affected different aspects of the nocturnal plasma melatonin profile suggesting that the amplitude of the melatonin rhythm may depend upon serotonin availability and/or melatonin metabolism whilst the onset of melatonin production depends upon noradrenaline availability.

Effect of Sodium Valproate on Nocturnal Melatonin Sensitivity to Light in Healthy Volunteers

“…In relation to receptor adaptation, other drugs have different acute and chronic effects on melatonin secretion. For example, desipramine acutely increases melatonin synthesis (Franey et al, 1986;Kennedy and Brown, 1992;Skene et al, 1994) but after chronic treatment, melatonin is no longer elevated (Kennedy and Brown, 1992), an activity possibly associated with pinealocyte noradrenergic receptor downregulation. Pharmacokinetic effects of the drug do not account for the changes in melatonin concentration with recent evidence indicating melatonin is primarily metabolized by the cytochrome P4501A2 enzymes (Härtter et al, 2000(Härtter et al, , 2003, while valproate has no discernable effect on the activity of this enzyme (Wen et al, 2001).…”

A New Concept for Melatonin Deficit On Pineal Calcification and Melatonin Excretion

“…Special care was taken that subjects did not take any substances which are known to interfere with melatonin production and/or secretion, but which, among the general population, are sometimes not considered to be "medication," e.g., with respect to sleep: benzodiazepines (McIntyre et al 1988), antidepressants (Skene et al 1994), beta-blockers (Cowen et al 1985, and with respect to pain: anti-inflammatory drugs (Surrall et al 1987;Murphy et al 1994). Drugscreening in urine included benzodiazepines, barbiturates, cannabinoids, amphetamines, cocain and opiates.…”

The Novel Melatonin Agonist Agomelatine (S20098) Is an Antagonist at 5-Hydroxytryptamine2C Receptors, Blockade of Which Enhances the Activity of Frontocortical Dopaminergic and Adrenergic Pathways

“…Although the relationship between melatonin levels and clinical depressive states is unclear, decreases have been reported (Szymanska et al, 2001;Tuunainen et al, 2002). Furthermore, antidepressant treatment enhances melatonin levels, reflecting actions of noradrenaline (NA) at pineal ␤-adrenoceptors facilitatory to its secretion (Borjigin et al, 1999;Skene et al, 1999;Szymanska et al, 2001). Melatonin acts via MT 1 and MT 2 receptors (Reppert, 1997;Borjigin et al, 1999), both of which control circadian rhythms (Liu et al, 1997).…”