The acute and chronic effects of (+) and (−) oxaprotiline upon melatonin secretion in normal subjects

Palazidou, Eleni; Skene, Debra J.; Arendt, Joséphine; Everitt, B. J.; Checkley, Stuart

doi:10.1017/s0033291700032736

Cited by 19 publications

(9 citation statements)

References 38 publications

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“…These observations are also supported by our previous findings that (+)-oxaprotiline, a potent and selective inhibitor of noradrenaline uptake, given at 21.00 h increased plasma melatonin concentrations whereas (-)-oxaprotiline, an inactive noradrenaline uptake inhibitor, had no effect on melatonin concentrations [14,17]. Given at 09.00 h neither of these drugs affected melatonin secretion [14].…”

Section: Discussionsupporting

confidence: 87%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Skene

Bojkowski

Arendt

1994

Brit J Clinical Pharma

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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.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

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

Skene

Bojkowski

Arendt

1994

Brit J Clinical Pharma

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“…[7][8][9] Accordingly, the influence of antidepressant drugs on the melatonin serum levels has been studied intensively. [10][11][12] A stimulating effect on the melatonin secretion was primarily found for desipramine 12 and (1)-oxaprotiline, 13 both inhibiting predominantly the norepinephrine (NA) reuptake. Because the nocturnal increase of melatonin is triggered by an adrenergic-cAMP mechanism, the effect of the NA-reuptake blockers was attributed to an elevated NA stimulus on NA receptors in the pineal gland.…”

mentioning

confidence: 99%

“…Because the nocturnal increase of melatonin is triggered by an adrenergic-cAMP mechanism, the effect of the NA-reuptake blockers was attributed to an elevated NA stimulus on NA receptors in the pineal gland. 13 The interpretation of reported effects of the selective serotonin reuptake inhibitors (SSRIs) was difficult because of conflicting results. Fluoxetine was found to negatively affect the melatonin secretion, 14 but fluvoxamine markedly increases the melatonin blood concentrations.…”

mentioning

confidence: 99%

Differential Effects of Fluvoxamine and Other Antidepressants on the Biotransformation of Melatonin

Härtter¹,

Wang²,

Weigmann³

et al. 2001

Journal of Clinical Psychopharmacology

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Melatonin, the predominant product of the pineal gland, is involved in the maintenance of diurnal rhythms. Nocturnal blood concentrations of melatonin have been shown to be enhanced by fluvoxamine, but not by other serotonin reuptake inhibitors. Because fluvoxamine is an inhibitor of several cytochrome P450 (CYP) enzymes, the authors studied the biotransformation of melatonin and the effects of fluvoxamine on the metabolism of melatonin in vitro using human liver microsomes and recombinant human CYP isoenzymes. Melatonin was found to be almost exclusively metabolized by CYP1A2 to 6-hydroxymelatonin and N-acetylserotonin with a minimal contribution of CYP2C19. Both reactions were potently inhibited by fluvoxamine, with a Ki of 0.02 microM for the formation of 6-hydroxymelatonin and 0.05 microM for the formation of N-acetylserotonin. Other than fluvoxamine, fluoxetine, paroxetine, citalopram, imipramine, and desipramine were also tested at 2 and 20 microM. Among the other antidepressants, only paroxetine was able to affect the metabolism of melatonin at supratherapeutic concentrations of 20 microM, which did not reach by far the magnitude of the inhibitory potency of fluvoxamine. The authors concluded that fluvoxamine is a potent inhibitor of melatonin degradation. Because this inhibitory action is also found in vivo, fluvoxamine might be used as an enhancer of melatonin, which might offer new therapeutic possibilities of fluvoxamine.

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“…Moreover, in the later hours, there was no significant increase in plasma melatonin levels, perhaps because of adaptive desensitization of pineal β-adrenoceptors to high levels of norepinephrine or because the peak capacity of the pineal gland to synthesize melatonin was reached 159. Like desipramine, fluvoxamine also had a positive effect on melatonin after acute administration,160 and the same results were found for both acute and chronic administration of oxaprotiline, a serotonin-norepinephrine reuptake inhibitor 161. A positive effect was found also for mirtazapine162 and clomipramine,163 but the latter was associated also with a normalization of pineal activity after long-term treatment.…”

Section: Therapeutic Actions Of Antidepressantsmentioning

confidence: 58%

Neuroimmune endocrine effects of antidepressants

Carvalho¹

2012

NDT

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Antidepressant pharmacotherapy is to date the most often used treatment for depression, but the exact mechanism of action underlying its therapeutic effect is still unclear. Many theories have been put forward to account for depression, as well as antidepressant activity, but none of them is exhaustive. Neuroimmune endocrine impairment is found in depressed patients; high levels of circulating corticosteroids along with hyperactivation of the immune system, high levels of proinflammatory cytokines, low levels of melatonin in plasma and urine, and disentrainment of circadian rhythms have been demonstrated. Moreover, antidepressant treatment seems to correct or at least to interfere with these alterations. In this review, we summarize the complex neuroimmune endocrine and chronobiological alterations found in patients with depression and how these systems interact with each other. We also explain how antidepressant therapy can modify these systems, along with some possible mechanisms of action shown in animal and human models.

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The acute and chronic effects of (+) and (−) oxaprotiline upon melatonin secretion in normal subjects

Cited by 19 publications

References 38 publications

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

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

Differential Effects of Fluvoxamine and Other Antidepressants on the Biotransformation of Melatonin

Neuroimmune endocrine effects of antidepressants

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