The effects of paroxetine and tianeptine on peripheral biochemical markers in major depression

Depression is related to the alterations of the central serotonergic system and some antidepressants achieve their therapeutic effects through alteration of serotonin (5-HT) (re)uptake. Peripheral biochemical markers, platelet and serum 5-HT concentrations, platelet monoamine oxidase (MAO) activity, plasma levels of cortisol and prolactin (PRL), were investigated in patients with major depression before and after 4 weeks of treatment with paroxetine (an inhibitor of 5-HT uptake) or tianeptine (a stimulator of 5-HT uptake). Study was open, single center and included female depressed patients, 21 treated with tianeptine (37.5 mg/day) and 15 treated with paroxetine (20 mg/day), and 11 drug-free healthy women (controls). Before treatment, depressed patients as a group had significantly higher serum 5-HT and cortisol concentrations than healthy controls. There were no differences in the other biochemical markers. Response to antidepressant treatment was estimated according to the 50% fall in the initial scores of Hamilton Depression Rating Scale (HAMD) after 4 weeks of treatment. Good therapeutic response was observed in 47% and 45% patients treated with paroxetine and tianeptine, respectively. Paroxetine treatment induced significant decrease in platelet 5-HT concentrations in both responders and nonresponders, while no alterations in platelet 5-HT values were found in tianeptine-treated patients. There was a subgroup of depressed patients in paroxetine-treated group with high pretreatment platelet 5-HT concentration and later poor therapeutic response to paroxetine treatment. Serum 5-HT values, platelet MAO activity or plasma cortisol or PRL levels were unchanged after both treatments. The results suggest that pretreatment platelet 5-HT levels, but not other peripheral biochemical markers, might predict therapeutic outcome at least in paroxetine-treated patients.     

Platelet MAO deamination of serotonin in depressed patients. Changes after imipramine treatment and clinical correlations

Monoamine oxidase (MAO) in blood platelets has been used as a model to study MAO in the central nervous system, where disorders in serotonergic systems are thought to occur in depression. Inconsistent changes in platelet MAO of depressed patients have been reported when several substrates other than serotonin (5-HT) have been used. To correlate changes in platelet MAO activity with the enzyme activity in central serotonergic systems, the platelet MAO activity of depressed patients (first unmedicated and then after 3 weeks and 2 months of imipramine treatment) and normal controls was measured using 5-HT as substrate. The results showed that there is a steady, measurable platelet MAO activity with that substrate. This activity was significantly higher in unmedicated depressed patients than in controls, and it decreased progressively with imipramine treatment, reaching a normal level when the patients were clinically recovered from depression after 2 months of therapy.     

Pretreatment platelet 5-HT concentration predicts the short-term response to paroxetine in major depression. Grupo de Trastornos Afectivos.

BACKGROUND: A previous retrospective study revealed that a high pretreatment platelet serotonin (5-HT) concentration was associated with a low response to serotonergic antidepressants in drug-free major depressives. We have examined such a relationship in depressive patients treated with paroxetine. METHODS: Seventy-four drug-free major depressives (DSM-IV) were admitted to the study. Clinical ratings were performed and blood was drawn prior to the initiation of treatment and after 4 weeks of paroxetine (20 mg/day). The concentrations of 5-HT, 5-hydroxyindoleacetic acid, and tryptophan were determined in plasma and blood. RESULTS: Paroxetine treatment reduced platelet 5-HT to 17% of baseline after 4 weeks of treatment. Responder patients had a pretreatment platelet 5-HT concentration 22% lower than nonresponders (p < .035). Admission HAMD scores, plasma paroxetine concentration, or platelet 5-HT concentration at endpoint did not differ between responders and nonresponders. Yet, the response rate was 11% in patients with high pretreatment platelet 5-HT (> 900 ng/10(9) platelets) and 50% in those below that value (p < .004). CONCLUSIONS: These findings support that depressed patients with a high pretreatment platelet 5-HT concentration have a poor therapeutic outcome after treatment with a standard paroxetine dose. These differences may be related to the existence of molecular differences in the 5-HT transporter.     

Platelet serotonergic markers in posttraumatic stress disorder

The neurobiological basis of posttraumatic stress disorder (PTSD) is believed to involve alterations in different neurotransmitter systems, and recent studies elucidated the role of serotonin (5-hydroxytryptamine, 5-HT) in PTSD. The data on the role of 5-HT have been obtained using blood platelets as a peripheral model for central serotonergic neurons. The reports suggested that platelet 5-HT concentration and monoamine oxidase (MAO) activity might serve as biological, even trait, markers for particular mental disturbances. Since the data on the peripheral serotonergic markers in PTSD subjects are controversial, the aim of the study was to determine platelet 5-HT concentration and platelet MAO activity in war veterans with PTSD, war veterans who did not develop PTSD, and in war veterans who were prisoners of war and developed PTSD. Platelet 5-HT concentration and MAO activity did not differ significantly between war veterans with or without PTSD, and prisoners of war with PTSD. Clinician-Administered PTSD Scale (CAPS) scores did not differ between war veterans with PTSD and prisoners of war, but Montgomery-Asberg Depression Rating Scale (MADRS) scores were significantly higher in prisoners of war who developed PTSD than in war veterans with PTSD. There was no significant correlation between platelet 5-HT concentration or platelet MAO activity and CAPS or MADRS scores within these groups. Platelet 5-HT concentration was slightly higher and platelet MAO activity slightly lower in prisoners of war with PTSD, than in all other groups. These findings suggest that platelet 5-HT concentration and platelet MAO activity are not altered in three drug-free groups--war veterans who did or did not develop PTSD, or in prisoners of war with PTSD--and that these platelet serotonergic markers are not associated with symptoms of PTSD or comorbid depression.     

Influence of clozapine on platelet serotonin, monoamine oxidase and plasma serotonin levels

The purpose of this study was to investigate the influence of clozapine on plasma serotonin, platelet serotonin and monoamine oxidase (MAO) levels in schizophrenic patients and to compare their results with those of unmedicated healthy controls. Groups of 20 outpatients with schizophrenia and 20 healthy controls matched for age, sex and smoking status were recruited for the study. Psychopathology, neurocognitive functioning, plasma serotonin, platelet serotonin and MAO levels were assessed after 1-week drug free interval, and 8 weeks after initiation of clozapine treatment in an open design. The mean clozapine dose at week 8 was 382.5+/-96.4 (range: 250-600) mg/day. In the patient group, at baseline, plasma serotonin and platelet MAO levels were significantly lower, and platelet serotonin levels were significantly higher than in controls. After 8 weeks of clozapine treatment, plasma serotonin and platelet MAO levels increased significantly, while a significant decrease in platelet serotonin levels was detected compared with baseline values. Baseline platelet MAO levels explained 22% of the variance in Clinical Global Impression - Improvement (CGI-I) and improvement in attention, while baseline platelet serotonin predicted 23% of the variance in the improvement in positive symptoms during clozapine treatment. Our data indicate that clozapine may be reversing or compensating for a pre-existing alteration in serotonergic neurotransmission in schizophrenic patients. The prediction of response to clozapine through peripheral biochemical markers may have important clinical implications if repeated in larger samples.     

Platelet MAO activity during treatment with pegylated interferon-alfa in melanoma patients

Depression and cognitive disturbance are well-known neuropsychiatric side effects of therapy with interferon-alfa (IFN-alfa). Aggression and irritability are also reported as side effects. Probably, central nervous system (CNS) serotonergic dysfunction is one of the underlying pathophysiological mechanisms of IFN-alfa-induced neuropsychiatric toxicity. Platelet activity of monoamine oxidase-B (MAO; EC1.4.3.4) is a possible indicator of central serotonergic function. Moreover, low platelet MAO activity is linked to impulsiveness, addiction and personality disorder. In this exploratory study in 17 high-risk melanoma patients, platelet counts, whole blood MAO, and platelet MAO activity were measured before and during therapy with IFN-alfa. Patients were randomized to treatment either with pegylated IFN-alfa (PEG-IFN-alfa) once a week at a dose of 6 microg/kg/week subcuteanously (s.c.) during 8 weeks, followed by a maintenance treatment of 3 microg/kg/week s.c. for a total of 5 years, or to observation only. Blood samples were taken at baseline, 4 and 8 weeks and 3 months. During treatment with IFN-alfa, platelet counts decreased at 4 and 8 weeks and 3 months, while platelet MAO activity increased, both compared to baseline and compared to non-treated controls. Compared to non-treated controls, platelet MAO activity increased with 86.4% (95 CI: 52.9-127.2). No significant changes in platelet MAO activity were observed in the control group. This indicates that platelet MAO activity is influenced by IFN-alfa. Since platelet MAO activity is a model for CNS MAO-B activity, it may be speculated that CNS MAO-B activity will also be increased. This could influence serotonin (5-HT) metabolism and thereby contribute to the development of psychiatric disturbance. However, a preferential inhibition of platelet production cannot be ruled out. Hypothetically, the antiproliferative effects of IFN-alfa could interfere more strongly with the synthesis of platelets than with the synthesis of mitochondria. In that case, increased platelet MAO activity reflects an increased number of mitochondria per platelet.     

Platelet MAO and amitriptyline treatment

Some tricyclic antidepressants have been reported to inhibit monoamine oxidase (MAO) activity in vitro in addition to blocking the reuptake of norepinephrine and/or serotonin. While the inhibition of MAO is reversible, platelet MAO activity in depressed patients responding to amitriptyline treatment has been reported to be reduced after drug treatment. In a reverse design, we measured platelet MAO activity and drug levels in patients chronically being treated with amitriptyline and again 2 and 4 weeks after stopping the medication. Although tricyclic drug concentrations were initially within the therapeutic range and undetectable on placebo treatment, platelet MAO activities were unchanged.     

Maternal sertraline treatment and serotonin transport in breast-feeding mother-infant pairs

OBJECTIVE: Pharmacological treatment of postpartum depression is frequently complicated by the mother's desire to breast-feed. Although breast milk levels of several selective serotonin reuptake inhibitors (SSRIs) have been reported to be relatively low, a critical question is whether SSRI exposure during nursing results in clinically significant blockade of serotonin (5-HT) reuptake in infants. This study determined the degree of transporter blockade in infants exposed to sertraline through maternal breast milk. METHOD: The extent of maternal and infant transporter blockade was assessed by measurement of platelet levels of 5-HT in 14 breast-feeding mother-infant pairs before and after 6-16 weeks of maternal treatment with sertraline for major depression with postpartum onset. Plasma sertraline and desmethylsertraline levels were obtained in 13 of these mothers and 11 of their infants. RESULTS: Marked declines in platelet 5-HT levels of 70%-96% were observed in mothers after sertraline treatment, 25-200 mg/day. In contrast, infants showed little or no change in platelet 5-HT levels after exposure through breast-feeding. Mean levels of maternal plasma sertraline and its major metabolite, desmethylsertraline, were 30.7 ng/ml and 45.3 ng/ml, respectively. Drug and drug metabolite concentrations in the infants were at or below the lower limit of quantitation. CONCLUSIONS: The data indicate that while mothers receiving clinical doses of sertraline experience substantial blockade of the platelet 5-HT transporter, platelet 5-HT uptake in nursing infants of treated mothers is unaltered. The observations suggest that mothers taking sertraline can breast-feed without appreciably affecting peripheral or central 5-HT transport in their infants.     

The effect of paroxetine on 5-HT(2A) receptors in depression: an [(18)F]setoperone PET imaging study

OBJECTIVE: In the cortex of animals, serotonin (5-HT) levels increase after several weeks of treatment with selective serotonin reuptake inhibitors (SSRIs). Studies using an intrasubject design to examine the effects of SSRI treatment on 5-HT(2A) receptors in the cortex of drug-free depressed patients are needed. In theory, agonist stimulation of 5-HT(2A) receptors could be relevant to SSRI treatment by promoting neuronal growth and survival as well as direct elevation of mood. The objective of this study was to evaluate the effect of 6 weeks of paroxetine treatment on 5-HT(2A) receptors in depressed patients. METHOD: After a medication-free period of at least 3 months, 19 depressed patients were treated for 6 weeks with paroxetine, 20 mg/day. The authors used [(18)F]setoperone and positron emission tomography to assess 5-HT(2A) receptor binding potential in the patients before and after treatment and in 19 age-matched healthy subjects. RESULTS: 5-HT(2A) binding potential declined with age in all cortical regions in the depressed and healthy subjects. There was a significant interaction between age and treatment effect on 5-HT(2A) binding potential in all cortical regions. Subjects aged 20 to 30 years had a 10% decrease in 5-HT(2A) binding potential after treatment, whereas subjects aged 30 to 40 had no change. No regional differences in 5-HT(2A) binding potential between depressed and healthy subjects were found. CONCLUSIONS: 5-HT(2A) receptors down-regulate in young depressed subjects after treatment with paroxetine, but this down-regulation attenuates with age. This suggests that over 6 weeks paroxetine treatment increases 5-HT agonism on 5-HT(2A) receptors in the cortex of young patients with depression.     

Platelet activation in depression and effects of sertraline treatment: An open-label study

OBJECTIVE: The authors' goal was to determine whether sertraline attenuates the increased platelet activation seen among depressed patients. METHOD: They tested 21 otherwise healthy patients with untreated major depressive episode who were 25-52 years old and 21 age- and sex-matched comparison subjects. Patients received 6 weeks of sertraline treatment, and 17 returned for retesting. RESULTS: At baseline, the depressed patients had greater platelet secretion than the comparison subjects in response to collagen. Depressed patients with a family history of coronary disease had nonsignificantly greater wound-induced fibrinogen receptor binding than the other subjects. Platelet secretion in response to collagen was significantly reduced after treatment with sertraline. CONCLUSIONS: Sertraline diminished the increased platelet secretion found among depressed patients, although the findings are limited by a lack of a placebo control group.     

Growth hormone, cortisol and prolactin responses to physical exercise: higher prolactin response in depressed patients

This study was designed to compare growth hormone, cortisol and prolactin responses to physical exercise in depressed patients and healthy comparison subjects. Patients fulfilled the DSM-IV diagnostic criteria for current major depressive disorder; subjective depressive symptoms were rated with Montgomery-Asberg Depression Rating Scale (MADRS) immediately before the experiment. Growth hormone, cortisol and prolactin were measured before and immediately after physiologically stressful bicycle cardiopulmonary exercise test. After exercise, there were three additional hormone measurements, with 30-min intervals. No significant difference was found in baseline growth hormone, cortisol or prolactin levels between patients and the control group. Plasma growth hormone and cortisol levels increased significantly during physical exercise in both patients and controls and returned to baseline in 90 min. There was no significant difference in growth hormone or cortisol responses to physical exercise between the two groups. However, prolactin levels increased only in the depressed patients group during the exercise. We hypothesize that acute exercise may have a stronger effect on serotonin (5-HT) release in depressed patients, which is reflected in increased plasma prolactin concentration.     

Evidence of the dual mechanisms of action of venlafaxine

BACKGROUND: Indirect evidence suggests that the antidepressant venlafaxine hydrochloride selectively inhibits serotonin (5-HT) uptake at low doses, whereas at high doses, it inhibits both 5-HT and norepinephrine (NE) uptake. We hypothesized that, in vivo, both high and low doses would inhibit the 5-HT uptake of platelets but that the higher dose would differentially blunt the pressor response to tyramine, a marker for NE uptake. METHODS: Healthy male volunteers aged 18 to 45 years received either 75 mg or 375 mg of venlafaxine hydrochloride per day, the 5-HT uptake inhibitor sertraline hydrochloride (50 mg/d), or the NE uptake inhibitor maprotiline hydrochloride (150 mg/d) (n = 8 for each of 4 treatment groups). Changes in platelet 5-HT uptake and the pressor response to intravenous tyramine were assessed following the initial dose and after 1 and 2 weeks of drug administration. RESULTS: Platelet 5-HT uptake was inhibited by venlafaxine across the dose range and by sertraline but not maprotiline. Inhibition was competitive, related to increases in affinity and not related to capacity. Steady-state drug levels were associated with a 5-HT uptake inhibition of 87% or more in subjects taking venlafaxine or sertraline. The pressor response to tyramine differentially distinguished maprotiline from sertraline and the low dose of venlafaxine but not from the high dose of venlafaxine. CONCLUSION: This study provides the first in vivo evidence in healthy humans that both 5-HT uptake and NE uptake inhibition are mechanisms of action sequentially engaged by venlafaxine over its clinically relevant dose range.     

Effects of sertraline treatment on plasma cortisol, prolactin and thyroid hormones in female depressed patients

The aim of the study was to evaluate the effects of 4 and 24 weeks of sertraline treatment (average dose 42.5 mg/day) on plasma hormone levels in 15 female patients with major depression. Baseline levels of triiodothyronine (T(3)) were lower, while cortisol, prolactin (PRL), thyroid-stimulating hormone (TSH), and thyroxin (T(4)) levels did not differ from the values in 16 female controls. There was a positive correlation between the scores on the Montgomery-Asperg Depression Rating Scale and baseline cortisol levels. Treatment with sertraline for 4 weeks increased plasma cortisol levels, while 24 weeks of sertraline treatment increased plasma T(3) levels in depressed patients. Neither 4, nor 24 weeks of sertraline treatment affected PRL, T(4) and TSH levels in depressed patients. The data show different and time-dependent effects of sertraline treatment on plasma cortisol, PRL and thyroid hormones in female depressed patients.     

Biochemical changes during clomipramine treatment of childhood obsessive-compulsive disorder

Peripheral measures of serotonergic and noradrenergic function were obtained in 29 obsessive-compulsive adolescents and 31 age- and sex-matched controls, as well as in a subsample of 22 patients after five weeks of treatment with clomipramine hydrochloride (134 +/- 33 mg/d) (mean +/- SD) given in a double-blind placebo-controlled trial. Drug-free obsessive-compulsive subjects did not differ from controls on measures of platelet serotonin and monoamine oxidase (MAO) activity, nor on plasma epinephrine or norepinephrine concentrations at rest and after a standard orthostatic challenge procedure. Compared with placebo, treatment with clomipramine was clinically effective and produced a marked decrease in platelet serotonin concentration, a trend toward a reduction in platelet MAO activity, and a rise in standing plasma norepinephrine. Clinical improvement during drug therapy was closely correlated with pretreatment platelet serotonin concentration and MAO activity, as well as with the decrease in both measures during clomipramine administration. This suggests that the effects of clomipramine on serotonin uptake may be essential to the antiobsessional action observed.     

THE EFFECT OF A 5HT2 RECEPTOR ANTAGONIST SARPOGRELATE (MCI-9042) TREATMENT ON PLATELET FUNCTION IN BUERGER''S DISEASE

The effect of a new, specific 5-HT₂ receptor antagonist sarpogrelate (MCI-9042) treatment on platelet function and serotonin levels in both plasma and whole blood in Buerger's disease, was assessed in a pilot study. We investigated 10 patients suffering from Buerger's disease. Sarpogrelate in a dose of 3 × 100mg a day was given p.o. for a period of 8 weeks. It was well tolerated and no major side effects were noted. It was judged to be effective in some patients as assessed by its effect on both subjective complaints and objective evaluation of ankle pressure index (API). Sarpogrelate induced a significant decrease in plasma serotonin (5-HT) concentration starting after the 4th week which lasted through to the 8th week of the study, whereas plasma tryptophan concentration increased significantly after 2 and 4 weeks. There were no changes in plasma 5-HIAA concentration. On the other hand whole blood 5-HT concentration increased significantly after 2 weeks, and there was also a tendency to increase in whole blood tryptophan concentration (p=0.052). Platelet aggregation induced by ADP and collagen did not show any statistically significant changes. Surprisingly, platelet aggregation induced by serotonin increased significantly after 2 weeks and even more so after 4 weeks of treatment, and then it returned to baseline values after 8 weeks. There was no effect on platelet count, APTT, TT and fibrinogen concentration. Copyright © 1996 Elsevier Science Ltd     

Blood monoamine metabolism in Huntington's disease

In 25 patients with Huntington's disease (HD), the mean blood concentration of serotonin (5-HT) and percentage of plasma free tryptophan were significantly increased while plasma concentrations of total and protein-bound tryptophan were significantly decreased. The pattern of changes in tryptophan concentrations was related to clinical severity but not to 5-HT levels. Platelet monoamine oxidase (MAO) activity was significantly increased in patients with HD; kinetic and marker enzyme studies suggested an increased enzyme concentration. Offspring at risk for HD also had elevated platelet MAO activity but normal concentrations of blood 5-HT and plasma tryptophan. In ten patients, plasma epinephrine concentrations were significantly increased; plasma dopamine and norepinephrine concentrations were positively related to MAO activity. The finding of peripheral neurotransmitter abnormalities in HD raises the question of an interaction between CNS and peripheral processes or a systemic disorder of neurotransmitter metabolism.     

Decreased serum semicarbazide sensitive aminooxidase (SSAO) activity in patients with major depression

Semicarbazide sensitive aminooxidase (SSAO) is known to interplay with monoamine oxidases (MAO) and several antidepressants. Taking into account the monoamine hypothesis concerning the pathophysiology of depression, the aim of the present pilot study was to evaluate serum SSAO activity in depressed patients. A total of 21 inpatients with major depression and 41 healthy controls were studied. Serum SSAO activity was determined by HPLC on days 1, 5 and 10 of inpatient treatment. At baseline without medication including antidepressants, highly depressed patients (MADRS score>or=30) had significantly decreased serum SSAO activity (mean 385+/-161 mU/l) when compared to healthy controls (mean 526+/-141 mU/l; p=0.003). This SSAO decrease was less pronounced at day 5 and day 10 under an antidepressive drug regime. Decreased serum SSAO activity was observed in patients with major depression, especially in those with high MADRS scores. The present results support the hypothesis of dysfunctional monoaminergic metabolism in the pathogenesis of depressive disorders. The disputable association between depression and monoamine metabolism requires further investigation, particularly with regard to SSAO activity and medication status.     

Relationship between parameters of serotonin transport and antidepressant plasma levels or therapeutic response in depressive patients treated with paroxetine and amitriptyline.

In a double-blind clinical study, antidepressant plasma levels, parameters of platelet serotonin (5-HT) transport (Km, Vmax and basal platelet 5-HT content) and therapeutic response were measured in depressive patients treated with either paroxetine (30 mg/day) or amitriptyline (150 mg/day) for 6 weeks. No correlation could be found between paroxetine plasma levels and therapeutic outcome after 2, 4 and 6 weeks of treatment. In contrast to the amitriptyline group, a marked increase in Km from baseline to week 2 was determined in paroxetine-treated patients, with Km increase being correlated with paroxetine plasma levels at week 2. However, no significant relationship could be found between 5-HT transport parameters and any of the outcome measures in either treatment group.     

Platelet serotonin and plasma prolactin and cortisol in healthy, depressed and schizophrenic women

Serotonin (5-hydroxytryptamine, 5-HT) is involved in the regulation of hypothalamic-pituitary-adrenal axis (HPA) activity and prolactin (PRL) secretion. The present study examined the relationship between platelet 5-HT and plasma cortisol and PRL concentrations in 20 schizophrenic, 25 depressed, and 25 healthy women. At the time of blood sampling, the schizophrenic and depressed patients had been drug-free for at least 7 days. Platelet 5-HT, plasma cortisol and PRL concentrations were determined by spectrofluorimetric, radioimmunoassay and immunoradiometric methods, respectively. Platelet 5-HT concentration was significantly higher in schizophrenic patients than in depressed patients or in healthy controls, while it was significantly lower in depressed patients than in healthy controls or in schizophrenic patients. Plasma cortisol levels were significantly increased both in schizophrenic and in depressed patients compared with values in healthy controls. Values of plasma PRL were similar across groups. A significant correlation was found between platelet 5-HT and plasma cortisol, and platelet 5-HT and plasma PRL concentrations in healthy controls, but not in schizophrenic or depressed patients. There was no significant relationship between plasma PRL and cortisol levels in any of the groups. Our data, although obtained on peripheral biochemical markers, indicate that depression and schizophrenia are characterized by disturbed 5-HT transmission and dysregulated HPA axis activity.     

Human plasma melatonin is elevated during treatment with the monoamine oxidase inhibitors clorgyline and tranylcypromine but not deprenyl

Melatonin was measured in plasma collected between 8:00 and 8:30 a.m. from 27 depressed patients studied before and after 21- to 24-day treatment with three monoamine oxidase (MAO) inhibitors. Baseline plasma melatonin concentrations determined by radioimmunoassay were 4.0 +/- SD 4.7 pg/ml. Tranylcypromine, a nonselective MAO inhibitor given in doses of 20-40 mg/day for 3 weeks, significantly elevated plasma melatonin to 10.6 +/- SD 2.0 pg/ml. Clorgyline, given in doses of 15-30 mg/day for 3 weeks, produced a significant, approximately three-fold increase in plasma melatonin (13.6 +/- SD 13.5 pg/ml). This clorgyline dose was selective for MAO type A inhibition, as MAO-B activity measured in platelets from the same blood samples was unaffected by clorgyline. In contrast, the selective MAO-B inhibitor deprenyl (10-30 mg/day for 3 weeks) led to a 96 +/- 4% inhibition of platelet MAO-B activity but no significant change in plasma melatonin (5.1 +/- SD 4.2 pg/ml). As both serotonin and norepinephrine are preferentially metabolized by MAO-A rather than MAO-B, an increased availability of serotonin (the precursor of melatonin) or enhanced noradrenergic function might mediate the melatonin changes observed to follow MAO-A but not MAO-B inhibition.