• The Korean Journal of Physiology and Pharmacology
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• v.21 no.2
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• pp.225-232
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• 2017

We demonstrated the effect of nortriptyline, a tricyclic antidepressant drug and serotonin reuptake inhibitor, on voltage-dependent $K^+$ (Kv) channels in freshly isolated rabbit coronary arterial smooth muscle cells using a whole-cell patch clamp technique. Nortriptyline inhibited Kv currents in a concentration-dependent manner, with an apparent $IC_{50}$ value of $2.86{\pm}0.52{\mu}M$ and a Hill coefficient of $0.77{\pm}0.1$. Although application of nortriptyline did not change the activation curve, nortriptyline shifted the inactivation current toward a more negative potential. Application of train pulses (1 or 2 Hz) did not change the nortriptyline-induced Kv channel inhibition, suggesting that the effects of nortiprtyline were not use-dependent. Preincubation with the Kv1.5 and Kv2.1/2.2 inhibitors, DPO-1 and guangxitoxin did not affect nortriptyline inhibition of Kv channels. From these results, we concluded that nortriptyline inhibited Kv channels in a concentration-dependent and state-independent manner independently of serotonin reuptake.

• Korean Journal of Biological Psychiatry
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• v.8 no.2
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• pp.266-270
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• 2001

Objective : The purpose of this study was to compare the plasma amitriptyline and nortriptyline level between before and after fluoxetine addition with patients who were currently taking amitriptyline. Method : From the inpatient and outpatient unit of Soon Chun Hyang University Hospital, Chunan, fourteen subjects who were taking amitriptyline 25mg more than 1 week at least were given fluoxetine 20mg. Before and 2 weeks after fluoxetine addition, the plasma level of amitriptyline and nortriptyline are analyzed simultaneously by High Performance Liquid Chromatography(HPLC). At the same times, HAM-D(Hamilton Rating Scale for Depression) score and the UKU(Uldvalg for Klinske Unders${\Phi}$ gelser) side effect scale were checked. Results : After fluoxetine addition to the patients who were taking amitriptyline, the plasma level of amitriptyline, nortriptyline and sum of amitriptyline and nortriptyline had risen. The mean plasma amitriptyline level increased from $168.9{\pm}89.4ng/ml$ to $183.0{\pm}102.0ng/ml$ after fluoxetine addition(p=0.011), but the change was not statistically significant. The mean plasma nortriptyline level increased significantly from $114.3{\pm}70.2ng/ml$ to $168.0{\pm}86.2ng/ml$ after fluoxetine addition(p=0.011). In addition, the mean plasma level of total amitriptyline and nortriptyline increased significantly from $283.1{\pm}125.3ng/ml$ to $350.9{\pm}78.4ng/ml$ after fluoxetine addition(p=0.016). After fluoxetine addition, no significant change was noted in the UKU side effect scale score. Conclusion : As consequence of comparison of plasma amitriptyline and nortriptyline level before and after fluoxetine addition, mean amitriptyline, nortriptyline and total plasma level was increased after fluoxetine addition. This suggests that coadministration of amitriptyline and fluoxetine may induce improvement of depressive symptom in depressive patients by way of increased plasma level of amitriptyline.

• Bulletin of the Korean Chemical Society
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• v.33 no.7
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• pp.2163-2167
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• 2012

A rapid, specific, and reliable LC-MS/MS-based bioanalytical method was developed and validated in rat plasma for the simultaneous quantitation of amitriptyline and its metabolite nortriptyline. Chromatographic separation of these analytes was achieved on a Gemini C18 column ($50{\times}4.60mm$, $5{\mu}m$) using reversed-phase chromatography. The mobile phase was an isocratic solvent system consisting of 1% formic acid in water and methanol (10:90, v/v), at a flow rate of 0.2 mL/min. The analytical range was set as 0.1-500 ng/mL for amitriptyline and 0.08-500 ng/mL for nortriptyline using a $200{\mu}L$ plasma sample. The accuracy and precision of the assay were in accordance with FDA regulations for the validation of bioanalytical methods. The validated method was successfully applied to a pharmacokinetic study in six rats after oral administration of amitriptyline (15 mg/kg). This method allows laboratory scientists to rapidly determine amitriptyline and nortriptyline concentrations in plasma.

• Archives of Craniofacial Surgery
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• v.21 no.4
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• pp.253-256
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• 2020

Parotid gland plays the most critical role in saliva secretion in the oral cavity. Parotid gland injuries due to facial trauma can cause various complications such as formation of a fistula or sialocele. Thus, such saliva-related complications can interfere with wound healing and increase the risk of infection. Several previous studies have discussed the treatment of fistula or sialocele. Nonetheless, prevention of such complications is of utmost importance. We present a case of parotid gland injury due to trauma to the cheeks that was surgically treated, with early postoperative management involving oral administration of nortriptyline and closed drainage, without complications.

• 대한임상약리학회:학술대회논문집
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• 1992.11a
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• pp.31-31
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• 1992

• YAKHAK HOEJI
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• v.57 no.4
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• pp.289-292
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• 2013

A total of 2,080 forensic autopsies in Seoul, Incheon and Gyeonggi province were performed by the National Forensic Service (NFS) in 2010. After analysing blood samples collected at autopsies by GC-MS and LC-MS/MS, the types and prevalence of drugs and poisons in blood were investigated using our laboratory information management system. Among 2,080 cases, 1,061 cases (51%) were positive for drugs and poisons. Surprisingly, antidepressants were identified in 137 cases which comprised 13% of the positive cases. Twelve different kinds of antidepressants were determined: Amitriptyline, fluoxetine, nortriptyline, trazodone, imipramine, mirtazapine, citalopram, venlafaxin, clomipramine, paroxetine, sertraline and bupropion. Amitriptyline was the most frequently detected antidepressant and was identified in 39 cases. Moreover, amitriptyline, fluoxetine, and nortriptyline were included in the list of the 20 most commonly encountered drugs or poisons in the analysis of blood collected at autopsies from 2007 to 2009, indicating the prevalence of their use. In this study, the 137 antidepressant-related deaths were classified by the mode of death to predict the prevalence of these drugs. As a result, those deaths were divided into four groups based on the cause and mode of death: 56 cases of suicide with fatal concentrations of antidepressant drugs in blood, 6 homicidal cases directly or indirectly related to antidepressants, 59 natural deaths with antidepressants detected in blood and 16 deaths caused by fire or other accidents with antidepressants detected in blood. Because incidents involving antidepressants have been increasing, especially in suicides or homicides, it is necessary for the health authorities and law enforcement administrations to cooperate and share the statistical data for curbing the abuse of antidepressants. This report is expected to provide the reference data related with antidepressants for the investigation of the deaths.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.195-195
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• 2001

The inhibitory potentials of TCAs (imipramine, desipramine, amitriptyline, and nortriptyline) on phenytoin p-hydroxylation and probe metabolic pathways of each CYP isoforms were evaluated from incubation studies of human liver microsomes and cDNA-expressed cytochrome P450s in vitro in order to understand the mechanism of drug interaction between TCAs and phenytoin, a substrate of CYP2C9 and CYP2C19. (omitted)

• YAKHAK HOEJI
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• v.43 no.3
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• pp.289-293
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• 1999

Many poly (vinyl chloride : PVC) membrane electrodes were investigated for the determination of basic drugs, chlorpromazine, amitriptyline, nortriptyline, etc. These electrodes are based on the use of the ion-association complexes of the basic drugs with eriochrome cyanine R, chromoxane cyanine, chrome azurol S and picric acid as ion-exchange sites in a plasticized PVC matrix. All ion-exchangers except picrate complex were not proper for use, because those complexes in plasticized membrane were excluded into aqueous working solution. These drug electrodes show excellent Nernstian responses in the concentration ranges $10^{-2}~10^{-6}$ mol $dm^{-3}$. Their selectivity with respect to each other, as well as their work-able pH range have been investigated. The major advantages of the proposed methods are their simplicity and speed.

• Korean Journal of Clinical Pharmacy
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• v.22 no.4
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• pp.356-366
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• 2012

Background: Chemotherapy-induced peripheral neuropathy (CIPN) involving sensory and motor nerve damage or dysfunction is a common and serious clinical problem that affects many patients receiving cancer treatment. This condition may pose challenges for the clinician to diagnose and manage, particularly in patients with coexisting conditions or disorders that involve the peripheral nervous system. Many chemotherapeutic agents used today are associated with the development of serious and dose-limiting CIPN that can adversely affect the administration of planned therapy and can impair quality of life by interference with the patients' activities of daily living. The most important clinical objective in the evaluation of patients with CIPN is to determine their level of functional impairment involving activities of daily living. These findings are used to make medical decisions to continue, modify, delay, or stop treatment. The most commonly reported drugs to cause CIPN include taxanes, platinum agents, vinca alkaloids, thalidomide, and bortezomib. We aimed to determine PN incidence during cisplatin, carboplatin and oxaliplatin administration. Methods: We collected data from 125 patients who received at least one cycle of cisplatin, carboplatin or oxaliplatin. They completed a self-reported questionnaire and items related to their disease and peripheral neuropathy. The investigators filled in part of items about disease and treatment. Patient Neurotoxicity Qeustionnaire developed by Bionumerik company were applied for PN assessment. Results: The incidences of sensory neurotoxicities of cisplatin, carboplatin and oxaliplatin were respectively 23%, 56% and 50%. The incidences of motor neurotoxicities of cisplatin, carboplatin and oxaliplatin were respectively 18%, 42% and 19%. The incidences of severe neurotoxicities of cisplatin, carboplatin and oxaliplatin were respectively 13%, 28% and 14%. The incidences of PN were associated with cumulative dose but not age, gender and concurrent illness. 19.2% of the patients (24/125) were prescribed with gabapentin, nortriptyline or gabapentin plus nortriptyline to reduce these peripheral symptoms and 75% of the patients answered the drug were effective. Conclusion: Incidence of PN after cisplatin or oxaliplatin administration is cumulative dose-related. Physician-based assessments under-reported the incidence and severity of CIPN. To overcome this limitation, diagnostic tools specifically designed to assess peripheral neuropathy severity associated with chemotherapy must be developed.

• Journal of Oral Medicine and Pain
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• v.44 no.3
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• pp.83-91
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• 2019

Purpose: Venlafaxine and duloxetine have been shown to be effective in the treatment of neuropathic pain disorders. However, knowledge about the efficacy of venlafaxine and duloxetine on burning mouth syndrome (BMS) is still insufficient. The purpose of this study was to investigate the efficacy of venlafaxine and duloxetine on refractory BMS patients. Methods: Twelve refractory BMS patients who were prescribed venlafaxine or duloxetine were included in this study. These patients did not respond to previous administration of clonazepam, alpha-lipoic acid, gabapentin, and nortriptyline. All participants were the primary type of BMS patients who had no local and systemic factors related to the oral burning sensation. The intensities of oral symptoms following venlafaxine or duloxetine administration were compared with those before administration and at baseline. Results: Venlafaxine and duloxetine were prescribed to four and nine patients, respectively. One patient was prescribed both medications in turn. Among them, only two patients showed improvement of oral symptoms without side effects. In the other ten patients, symptoms failed to improve. Six of them reported that the drug was ineffective, and four of them stopped taking the medications on their own due to intolerable side effects, such as insomnia, constipation, drowsiness, dizziness, and xerostomia. Conclusions: Venlafaxine and duloxetine may only relieve oral symptoms in a minority of refractory BMS patients. Further large-scale studies are needed to determine the potential clinical factors that could predict the efficacy of venlafaxine and duloxetine.