Time of Administration of Acute or Chronic Doses of Imipramine Affects its Antidepressant Action in Rats

Kawai, Hiroshi; Kodaira, Natsumi; Tanaka, Chika; Ishibashi, Takuya; Kudo, Naomi; Kawashima, Yasunaru; Mitsumoto, Atsushi

doi:10.5334/jcr.156

Cited by 10 publications

(10 citation statements)

References 55 publications

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“…In the present study, the SNRI venlafaxine showed peak antidepressant activity in the afternoon, whereas the SNRI milnacipran showed potent antidepressant activity in the morning in the FST in Wistar-Hannover rats (Kawai et al 2018a). The tricyclic antidepressant imipramine showed maximal antidepressant activity in the morning in rats (Kawai et al 2018b). In contrast, imipramine and amitriptyline showed maximal antidepressant activity in the evening in C57BL/6 mice (present study) and ICR mice (Ushijima et al 2005), respectively.…”

Section: Discussioncontrasting

confidence: 44%

“…In animal studies, amitriptyline and fluvoxamine were most effective in the early dark phase (Ushijima et al 2005), whereas nomifensine, milnacipran, and imipramine worked best in the light phase (Borsini et al 1990;Kawai et al 2018aKawai et al , 2018b. A behavioral test suggested that the serotonergic and noradrenergic activities of milnacipran may contribute toward its overall antidepressant activity in the morning and evening, respectively (Kawai et al 2018a).…”

Section: Introductionmentioning

confidence: 99%

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Antidepressants with different mechanisms of action show different chronopharmacological profiles in the tail suspension test in mice

Kawai

Iwadate

Ishibashi

et al. 2019

Chronobiology International

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The circadian system regulates sleep/wake cycles, metabolism, mood, and other functions. It also influences medication efficacy. In this study, we studied the chronopharmacological profiles of antidepressants with various modes of action. We also investigated the effects of dosing time on the pharmacological activity of several antidepressants acting on serotonergic, noradrenergic, and/or dopaminergic neurons. C57BL/6 mice were intraperitoneally administered fluoxetine, imipramine, venlafaxine, or bupropion at 08:00 h (morning), 14:00 h (mid-day), 20:00 h (evening), or 02:00 h (mid-night). Antidepressant activity was evaluated by the tail suspension test. All antidepressants reduced immobility, and their activities varied according to the dosing time. Fluoxetine and imipramine induced relatively strong rhythms with high amplitudes. Their maximal effects were observed in the morning and evening, respectively. Venlafaxine and bupropion induced weak rhythms with maximal effects in the evening and dawn, respectively. These results suggest that the antidepressant activity is associated with circadian fluctuation, and antidepressants with different modes of action have different chronopharmacological profiles. They affect locomotor activity in animals placed in novel (unfamiliar) environments. Fluoxetine, imipramine, and venlafaxine reduced locomotor activity, whereas bupropion increased it. The effects on locomotor activity also vary with circadian rhythm, and the tested drugs showed a maximal effect during the light phase. The peak time was different from that in TST. Plasma and brain levels of all drugs were slightly 3 higher in the morning than in the evening. The dosing time dependency of the antidepressant activity did not correlate with the sedative/stimulatory activity or tissue drug level. Therefore, these latter two factors may have only a small impact on circadian antidepressant activity fluctuations. The relative activity of the serotonergic, noradrenergic, and dopaminergic systems may determine the chronopharmacological profiles of each drug. These results suggest the possibility that drug therapy be optimized by considering the dosing time when the antidepressant activity is high and other pharmacological activities leading to adverse effects are low. Further studies using animal models of depression and in clinical settings are necessary to confirm the effects of dosing time on depressed subjects.

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Section: Discussioncontrasting

confidence: 44%

Section: Introductionmentioning

confidence: 99%

Antidepressants with different mechanisms of action show different chronopharmacological profiles in the tail suspension test in mice

Kawai

Iwadate

Ishibashi

et al. 2019

Chronobiology International

Self Cite

View full text Add to dashboard Cite

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“…Rodent models show that antidepressants are more effective at specific times of day (e.g. milnacipran, fluoxetine, imipramine, venlafaxine, or bupropion) (Kawai et al, 2018a(Kawai et al, , 2018b(Kawai et al, , 2019. There does not appear to be a common mode of circadian regulation as dosing time dependency is seen with drugs that have different modes of action in serotonergic, noradrenergic, and dopaminergic neurons.…”

Section: Timing Medicine Targeted To the Nervous Systemmentioning

confidence: 99%

“…There does not appear to be a common mode of circadian regulation as dosing time dependency is seen with drugs that have different modes of action in serotonergic, noradrenergic, and dopaminergic neurons. Moreover, drugs show different chrono-pharmacological profiles (Kawai et al, 2018a(Kawai et al, , 2018b(Kawai et al, , 2019. The action of neuropsychiatric drugs (eg, lithium, selective serotonin reuptake inhibitors [SSRIs]) is also affected by polymorphisms in circadian clock genes, chronotype, and cellular circadian rhythms, supporting a general role of circadian biology in neuropsychiatric disorders (Rybakowski et al, 2014;McCarthy et al, 2019).…”

Section: Timing Medicine Targeted To the Nervous Systemmentioning

confidence: 99%

Circadian Rhythms, Disease and Chronotherapy

2021

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Circadian clocks are biological timing mechanisms that generate 24-h rhythms of physiology and behavior, exemplified by cycles of sleep/wake, hormone release, and metabolism. The adaptive value of clocks is evident when internal body clocks and daily environmental cycles are mismatched, such as in the case of shift work and jet lag or even mistimed eating, all of which are associated with physiological disruption and disease. Studies with animal and human models have also unraveled an important role of functional circadian clocks in modulating cellular and organismal responses to physiological cues (ex., food intake, exercise), pathological insults (e.g. virus and parasite infections), and medical interventions (e.g. medication). With growing knowledge of the molecular and cellular mechanisms underlying circadian physiology and pathophysiology, it is becoming possible to target circadian rhythms for disease prevention and treatment. In this review, we discuss recent advances in circadian research and the potential for therapeutic applications that take patient circadian rhythms into account in treating disease.

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“…Complementarily, pharmacodynamic studies describe the association between drug concentrations and their effects [35]. The role of clock genes on antidepressant targets seem to influence antidepressant efficacy and side effects during the day [36,37].…”

Section: Introductionmentioning

confidence: 99%

Antidepressants and Circadian Rhythm: Exploring Their Bidirectional Interaction for the Treatment of Depression

2021

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Scientific evidence that circadian rhythms affect pharmacokinetics and pharmacodynamics has highlighted the importance of drug dosing-time. Circadian oscillations alter drug absorption, distribution, metabolism, and excretion (ADME) as well as intracellular signaling systems, target molecules (e.g., receptors, transporters, and enzymes), and gene transcription. Although several antidepressant drugs are clinically available, less than 50% of depressed patients respond to first-line pharmacological treatments. Chronotherapeutic approaches to enhance the effectiveness of antidepressants are not completely known. Even so, experimental results found until this day suggest a positive influence of drug dosing-time on the efficacy of depression therapy. On the other hand, antidepressants have also demonstrated to modulate circadian rhythmicity and sleep–wake cycles. This review aims to evidence the potential of chronotherapy to improve the efficacy and/or safety of antidepressants. It includes pre-clinical and clinical studies that demonstrate the relevance of determining the most appropriate time of administration for antidepressant drugs. In parallel, their positive influence on the resynchronization of disrupted circadian rhythms is also herein discussed. It is expected that this review will promote the investigation of chronotherapy for the treatment of depression, contribute to a better understanding of the relationship between antidepressants and circadian rhythms, and consequently promote the development of new therapeutics.

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Time of Administration of Acute or Chronic Doses of Imipramine Affects its Antidepressant Action in Rats

Cited by 10 publications

References 55 publications

Antidepressants with different mechanisms of action show different chronopharmacological profiles in the tail suspension test in mice

Antidepressants with different mechanisms of action show different chronopharmacological profiles in the tail suspension test in mice

Circadian Rhythms, Disease and Chronotherapy

Antidepressants and Circadian Rhythm: Exploring Their Bidirectional Interaction for the Treatment of Depression

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