Effects of repeated administration of amitriptyline on modulation of noradrenergic descending inhibitory system in a rat model of neuropathic pain

Hiroki, Tadanao

doi:10.26226/morressier.58f5b02ed462b80296c9e034

Cited by 6 publications

(11 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 In addition, amitriptyline is commonly used to treat neuropathic pain. 2 The major metabolic pathways that amitriptyline is involved in are demethylation mediated by the cytochrome P450 (CYP) 2C19 enzyme and hydroxylation mediated by the CYP2D6 enzyme ( Figure 1). 3 Amitriptyline is demethylated via CYP2C19 to nortriptyline, a pharmacologically active metabolite.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Quantitative Modeling Analysis Demonstrates the Impact of CYP2C19 and CYP2D6 Genetic Polymorphisms on the Pharmacokinetics of Amitriptyline and Its Metabolite, Nortriptyline

Koh

Pak

Choi

et al. 2018

The Journal of Clinical Pharma

View full text Add to dashboard Cite

Amitriptyline is a tricyclic antidepressant that is metabolized mainly by CYP2C19 and CYP2D6 enzymes. Higher plasma levels of amitriptyline and its active metabolite, nortriptyline, are associated with an increased risk of adverse events including anticholinergic effects. The aim of this study was to evaluate the effects of CYP2C19 and CYP2D6 genetic polymorphisms on amitriptyline and nortriptyline pharmacokinetics. Twenty‐four Korean healthy adult male volunteers were enrolled in the study after stratification by their CYP2C19 and CYP2D6 genotypes. Serial blood draws for pharmacokinetic analysis were made after a single oral 25‐mg dose of amitriptyline was administered. Plasma amitriptyline and nortriptyline concentrations were measured by a validated liquid chromatography with tandem mass spectrometry. Population pharmacokinetic modeling analysis was conducted using NONMEM, which evaluated the effects of CYP2C19 and CYP2D6 genotypes on amitriptyline and nortriptyline pharmacokinetics. The biotransformation of amitriptyline into nortriptyline was significantly different between subjects with the CYP2C19*2/*2, *2/*3, and *3/*3 genotypes and those with the other genotypes, with an estimated metabolic clearance of 17 and 61.5 L/h, respectively. Clearance of amitriptyline through pathways other than biotransformation into nortriptyline was estimated as 18.8 and 30.6 L/h for subjects with the CYP2D6*10/*10 and *10/*5 genotypes and those with the other genotypes, respectively. This study demonstrated a quantitative effect of the CYP2C19 and CYP2D6 genotypes on amitriptyline and nortriptyline pharmacokinetics. Production of nortriptyline from amitriptyline was associated with CYP2C19 genotypes, and clearance of amitriptyline through pathways other than biotransformation into nortriptyline was associated with CYP2D6 genotypes. These observations may be useful in developing individualized, optimal therapy with amitriptyline.

show abstract

mentioning

confidence: 99%

“…Amitriptyline is a tricyclic antidepressant that is widely prescribed for the treatment of psychiatric disorders, including major depression, obsessive‐compulsive disorder, panic attacks, and generalized anxiety disorder . In addition, amitriptyline is commonly used to treat neuropathic pain …”

mentioning

confidence: 99%

Quantitative Modeling Analysis Demonstrates the Impact of CYP2C19 and CYP2D6 Genetic Polymorphisms on the Pharmacokinetics of Amitriptyline and Its Metabolite, Nortriptyline

Koh

Pak

Choi

et al. 2018

The Journal of Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…Duloxetine is a serotonin noradrenaline reuptake inhibitor (SNRI) which inhibits serotonin (5-HT) and noradrenaline (NA) reuptake and is widely used in the treatment of chronic pain, including neuropathic pain ( Finnerup et al, 2015 ). Increase in NA concentrations in the spinal dorsal horn through reuptake inhibition is thought to be one of the analgesic mechanisms of duloxetine ( Hoshino et al, 2015 , Hiroki et al, 2017 ). Duloxetine was found to rapidly and significantly suppress mechanical hypersensitivity in an animal model of neuropathic pain ( Hoshino et al, 2015 , Hiroki et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

“…Increase in NA concentrations in the spinal dorsal horn through reuptake inhibition is thought to be one of the analgesic mechanisms of duloxetine ( Hoshino et al, 2015 , Hiroki et al, 2017 ). Duloxetine was found to rapidly and significantly suppress mechanical hypersensitivity in an animal model of neuropathic pain ( Hoshino et al, 2015 , Hiroki et al, 2017 ). However, in human patients, number needed to treat (NNT) of duloxetine is approximately 6 ( Finnerup et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

The efficacy of duloxetine depends on spinal cholinergic plasticity in neuropathic pain model rats

Kato

Suto

Obata

et al. 2022

IBRO Neuroscience Reports

View full text Add to dashboard Cite

“…BMS patients can also pose a therapeutic challenge to clinicians who are consulted to evaluate these patients [2]. Amitriptyline is widely used as an analgesic in chronic pain as it helps inhibit pain signals by activating descending pain inhibitory pathways [3]. Thus, amitriptyline has been a first-line treatment for BMS.…”

Section: Introductionmentioning

confidence: 99%

An increase in corrected QT interval may indicate a good clinical response to amitriptyline in female patients with burning mouth syndrome

Mikuzuki¹,

Aota²,

Toyofuku³

et al. 2018

NNB

View full text Add to dashboard Cite

Burning mouth syndrome (BMS) is characterized by a burning sensation of the oral mucosa in the absence of underlying causes. BMS patients can pose a therapeutic challenge to clinicians. Amitriptyline has been a first-line treatment for BMS and is known to prolong corrected QT interval (QTc) in a dose dependent manner. However, little is known about the QTc lengthening effect of amitriptyline at analgesic dosages. The objective of this study was to evaluate changes in QTc in female BMS patients treated with amitriptyline. We conducted a single-center retrospective observational study and evaluated 40 female BMS patients. The QTc interval did not show statistically significant increase with amitriptyline (p=0.1502). However, the change in QTc of amitriptyline-responders was significantly longer than that of nonresponders (p=0.0142). The change in QTc may be a non-invasive maker of clinical responses to amitriptyline in female BMS patients.

show abstract

Effects of repeated administration of amitriptyline on modulation of noradrenergic descending inhibitory system in a rat model of neuropathic pain

Cited by 6 publications

References 0 publications

Quantitative Modeling Analysis Demonstrates the Impact of CYP2C19 and CYP2D6 Genetic Polymorphisms on the Pharmacokinetics of Amitriptyline and Its Metabolite, Nortriptyline

Quantitative Modeling Analysis Demonstrates the Impact of CYP2C19 and CYP2D6 Genetic Polymorphisms on the Pharmacokinetics of Amitriptyline and Its Metabolite, Nortriptyline

The efficacy of duloxetine depends on spinal cholinergic plasticity in neuropathic pain model rats

An increase in corrected QT interval may indicate a good clinical response to amitriptyline in female patients with burning mouth syndrome

Contact Info

Product

Resources

About