Acute treatment with desipramine stimulates melatonin and 6‐sulphatoxy melatonin production in man.

Abstract

Acute administration of the antidepressant drug desipramine (DMI) in man, increased evening melatonin secretion, which reached peak plasma levels 2‐4 h earlier than after placebo administration. The increase at set time points 21.00 h‐22.00 h was directly proportional to an individual's integrated night‐time secretion of melatonin. We have shown that this stimulation was not an effect of DMI inhibition on the hepatic metabolism of melatonin to 6‐sulphatoxy melatonin (aMT6s), indeed aMT6s is in itself a good index of the evening melatonin rise. The stimulation of early evening melatonin by DMI might be exploited as a simple pineal function test.

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

“…Treatment with DMI in the late afternoon thus increased noradrenaline availability (by inhibiting its re-uptake) at a time of maximum receptor sensitivity. Both conditions appear to be necessary for stimulation of melatonin secretion as morning administration of DMI failed to affect plasma melatonin concentration [16].…”

“….. Figure 1 Mean hourly plasma melatonin concentrations (± s.e. mean) in eight healthy male subjects after desipramine (DMI) 100 mg (0), fluvoxamine 100 mg (A) or placebo (m) taken at 16.00 h. Two-way ANOVA indicated significant time-dependent effects of the treatments (P < 0.001).…”

“…Studies in our laboratory have shown that DMI, given as a single dose in the late afternoon, will increase melatonin secretion in the early evening [16]. In the present study we have compared the effects of these two antidepressant drugs, given as an acute dose in the early evening, on melatonin and cortisol production in the same individuals.…”

“…Many reports have shown that pharmacological treatments which increase the availability of biogenic amines, either by inhibition of re-uptake mechanisms [14][15][16][17], by inhibition of catabolism by monoamine oxidase [18,19] or by provision of extra precursor [12,13] will increase pineal melatonin secretion. However, the relative contributions of the noradrenergic and serotonergic input on the production of melatonin in humans have not been directly evaluated.…”

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).…”