Relationships between brain concentrations of desipramine and paradoxical sleep inhibition in the rat

Baumann, Pierre; Gaillard, Jean‐Michel; Perey, M; Justafré, J. C.; Le, P. K.

doi:10.1007/bf01243270

Cited by 20 publications

(13 citation statements)

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“…A single intraperitoneal dose of 4mg/kg of desipramine results in a 35-fold accumulation of desipramine in the brain tissue relative to whole blood and completely inhibits rapid eye movement sleep for five hours and partially for twelve hours (Baumann et al, 1983). During the time when rapid eye movement sleep is completely inhibited the concentration of desipramine in the No statistically significant difference.…”

Section: Discussionmentioning

confidence: 97%

Effects of monoamine uptake inhibitors given early postnatally on monoamines in the brain stem, caudate/putamen and cortex, and on dopamine D1 and D2 receptors in the caudate/putamen

Hilakivi

Ahtee

Rinne

et al. 1995

J. Neural Transmission

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Rats were treated with desipramine 5 mg/kg, nomifensine 10 mg/kg, zimelidine 25 mg/kg or with 0.9% sodium chloride once a day during the second and third weeks after birth, and brain stem, caudate/putamen and cortical monoamines, and caudate/putamen dopamine D1 (3[H]SCH 23390) and D2 (3[H]spiroperidol) receptor binding were measured when rats were at two months of age. In the brain stem, the concentration of 3-methoxy-4-hydroxy-phenyl glycol was increased in nomifensine rats and the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in zimelidine rats. In the caudate/putamen, the concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid and the ratio of homovanillic acid to dopamine were increased in desipramine rats; neither 3[H]SCH 23390 nor 3[H]spiroperidol binding were affected by any of the three monoamine uptake inhibiting antidepressants studied. In the cortex, the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in desipramine and zimelidine rats. The findings suggest that desipramine but not nomifensine increases the metabolism of dopamine in the caudate/putamen and nomifensine but not desipramine increases the metabolism of norepinephrine in the brain stem, and furthermore that the metabolism of serotonin is affected by desipramine as well as by zimelidine. It is possible that also treatment of women with these drugs during late pregnancy causes long-lasting changes in the brain of human fetus.

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Section: Discussionmentioning

confidence: 97%

Effects of monoamine uptake inhibitors given early postnatally on monoamines in the brain stem, caudate/putamen and cortex, and on dopamine D1 and D2 receptors in the caudate/putamen

Hilakivi

Ahtee

Rinne

et al. 1995

J. Neural Transmission

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“…Support for this comes from studies of NE reuptake inhibitors on sleep. Desipramine, Org 4428, and nortriptyline, for example, all significantly decrease REM time and REM% (Hishikawa et al 1965;Ross et al 1995;Baumann et al 1983;Dunleavy et al 1972;van Bemmel et al 1999;Buysse et al 1996;Reynolds et al 1997;Taylor et al 1999). Perhaps bupropion's main mechanism of action is not NE reuptake inhibition but some other unidentified NE or DA mechanism.…”

Section: Discussionmentioning

confidence: 99%

Effects of Rapid Tryptophan Depletion on Sleep Electroencephalogram and Mood in Subjects with Partially Remitted Depression on Bupropion

Evans

Golshan

Kelsoe

et al. 2002

Neuropsychopharmacology

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Serotonin has been implicated in both sleep and mood regulation. When central serotonin was depleted with a tryptophan-free amino acid drink (TFD),Serotonin (5-hydroxytryptamine; 5-HT) has long been implicated in the pathophysiology of depression as well as in the sleep and mood abnormalities associated with depression (Maes and Meltzer 1995). Specifically, deficiencies in 5-HT levels or in cellular responses to 5-HT neurotransmission are thought to be involved in depression. In support of this idea, deficiencies in 5-HT neurotransmission in various projections from the raphe nucleus can at least partially explain many of the common abnormalities seen in depression such as a depressed mood, decreased interest and pleasure, decreased appetite, and insomnia (Stahl 2000). Also commonly seen in depression are reduced rapid eye -Colin 1982;McCarley 1982;Jones 1991;Luebke et al. 1992).The rate of 5-HT synthesis is limited by the availability of its amino acid precursor, tryptophan. Rapid depletion of plasma tryptophan levels by administration of a tryptophan-free amino acid drink (TFD) depletes central 5-HT levels (Biggio et al. 1974;Moja et al. 1988). See Moore et al. (2000) for a recent review of the TFD literature.Consistent with the hypothesis that 5-HT inhibits REM sleep, Bhatti et al. (1998) found that a TFD decreased REM latency and increased REM% in normal male subjects. Voderholzer et al. (1998) found a significant increase in RD in 12 healthy subjects after TFD administration but saw no other significant REM changes. A study by Moore et al. (1998) found reduced RL and stage 2 percent (S2%) and increased REM% and RD after TFD administration in fully remitted depression patients on selective serotonin reuptake inhibitors (SSRIs). Additionally, in four patients treated with the monoamine oxidase inhibitor (MAOI), phenelzine, Landolt et al. (2000) showed increased REM time and REM% after TFD administration.With regard to mood, TFD studies have had mixed results when tested in normal subjects. One TFD study showed normal males having significantly increased scores on a depression scale, the Multiple Affect Adjective Checklist (MAACL), after TFD administration (Young et al. 1985). Benkelfat et al. (1994) also found decreased mood on the Profile of Mood States (POMS) in six out of 20 of his healthy male subjects with a multigenerational history of affective disorder. Additionally, Klaassen et al. (1999) found that TFD administration lowered mood in both subjects with and without a family history of affective disorders with the mood changes being significantly more evident in those with a family history. Ellenbogen et al. (1996) showed that healthy female subjects had significantly lower scores after a TFD on four of six scales on the bipolar form of the POMS including the depression scale. However, Ellenbogen et al. (1999) showed that normal females with a multi-generational family history of major affective disorders had no lowering of mood in response to a TFD. Quintin et al. (2001) showed a decline in mood as m...

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“…The plasma concentrations after their overdoses become significantly higher than those in the therapeutic use (Prouty and Anderson, 1990;Barbey and Roose, 1998;Rosenstein et al, 1993). As most antidepressants have highly lipophilic properties, they accumulate in the brain (Prouty and Anderson, 1990): namely, the brain-to-plasma ratios are approximately 13À20:1 for imipramine (Besret et al, 1996), 15À25 : 1 for desipramine (Baumann et al, 1983), 10À35 : 1 for amitriptyline (Glotzbach and Preskorn, 1982;Baumann et al, 1984;Miyake et al, 1990), 8À15 : 1 for nortriptyline (Baumann et al, 1984;Miyake et al, 1990), 10À48 : 1 for clomipramine (Friedman and Cooper, 1983;Eschalier et al, 1988), 44À59 : 1 for maprotiline (Miyake et al, 1991), and 4À8 : 1 for citalopram (Kugelberg et al, 2001). In addition, the mean brain concentrations of the Inhibition of GIRK channels by antidepressants T Kobayashi et al tricyclic antidepressants in postmortem humans were approximately 20 times higher than the corresponding blood levels (Prouty and Anderson, 1990).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of G Protein-Activated Inwardly Rectifying K+ Channels by Various Antidepressant Drugs

Kobayashi

Washiyama

Ikeda

2004

Neuropsychopharmacol

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G protein-activated inwardly rectifying K þ channels (GIRK, also known as Kir3) are activated by various G protein-coupled receptors. GIRK channels play an important role in the inhibitory regulation of neuronal excitability in most brain regions and the heart rate. Modulation of GIRK channel activity may affect many brain functions. Here, we report the inhibitory effects of various antidepressants: imipramine, desipramine, amitriptyline, nortriptyline, clomipramine, maprotiline, and citalopram, on GIRK channels. In Xenopus oocytes injected with mRNAs for GIRK1/GIRK2, GIRK2 or GIRK1/GIRK4 subunits, the various antidepressants tested, except fluvoxamine, zimelidine, and bupropion, reversibly reduced inward currents through the basal GIRK activity at micromolar concentrations. The inhibitions were concentration-dependent with various degrees of potency and effectiveness, but voltage-and time-independent. In contrast, Kir1.1 and Kir2.1 channels in other Kir channel subfamilies were insensitive to all of the drugs. Furthermore, GIRK current responses activated by the cloned A 1 adenosine receptor were similarly inhibited by the tricyclic antidepressant desipramine. The inhibitory effects of desipramine were not observed when desipramine was applied intracellularly, and were not affected by extracellular pH, which changed the proportion of the uncharged to protonated desipramine, suggesting its action from the extracellular side. The GIRK currents induced by ethanol were also attenuated in the presence of desipramine. Our results suggest that inhibition of GIRK channels by the tricyclic antidepressants and maprotiline may contribute to some of the therapeutic effects and adverse side effects, especially seizures and atrial arrhythmias in overdose, observed in clinical practice.

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Relationships between brain concentrations of desipramine and paradoxical sleep inhibition in the rat

Cited by 20 publications

References 19 publications

Effects of monoamine uptake inhibitors given early postnatally on monoamines in the brain stem, caudate/putamen and cortex, and on dopamine D1 and D2 receptors in the caudate/putamen

Effects of monoamine uptake inhibitors given early postnatally on monoamines in the brain stem, caudate/putamen and cortex, and on dopamine D1 and D2 receptors in the caudate/putamen

Effects of Rapid Tryptophan Depletion on Sleep Electroencephalogram and Mood in Subjects with Partially Remitted Depression on Bupropion

Inhibition of G Protein-Activated Inwardly Rectifying K+ Channels by Various Antidepressant Drugs

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