No abstract available.
Nortriptyline* ; Pharmacokinetics*

No abstract available.
Nortriptyline* ; Plasma*

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 IC₅₀ value of 2.86±0.52 µM and a Hill coefficient of 0.77±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.
Coronary Vessels ; Muscle, Smooth* ; Myocytes, Smooth Muscle* ; Nortriptyline* ; Serotonin

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+/-89.4ng/ml to 183.0+/-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+/-70.2ng/ml to 168.0+/-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+/-125.3ng/ml to 350.9+/-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 comparson 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.
Amitriptyline* ; Chungcheongnam-do ; Depression ; Fluoxetine* ; Humans ; Inpatients ; Nortriptyline ; Outpatients ; Plasma*

It was not above two or three decades from the changes began that regarding nicotine dependence as a kind of addictive disorder and a therapeutic target. Despite the short period of history, lots of medications were developed and showing significant clinical outcomes. In this review, we introduce the both of medications available at this time and in the status of developing for nicotine dependence. The clinical efficacies, practical ways of prescription, and common adverse events of the medications currently available are described through the survey of literatures. The novel medications in the process of developing are arranged by the proposed mechanism of action and summarized the phases of clinical trials at present. Among the diverse pharmacological tools now available, nicotine replacement and bupropion could be the first-line recommendation drugs and nortriptyline and clonidine could be the second-line recommendation drugs. Other medications like several antidepressants (e.g., moclobemide), buspirone, and naltrexone may be helpful in some specific population. Most of medications currently available have uncertainties in the aspects of their mechanisms of action except nicotine replacement materials; however, medications in developing have clearer neurobiological basis in their applications. Therefore, we can expect higher treatment outcomes by new products. Additionally, introduction of nicotine vaccines for high-risk group is drawing near. It could be possible for the individualizing for strategies of smoking cessation according to the patients' specific situation in a future.
Antidepressive Agents ; Bupropion ; Buspirone ; Clonidine ; Naltrexone ; Nicotine* ; Nortriptyline ; Prescriptions ; Smoking Cessation ; Tobacco Use Disorder* ; Vaccines

BACKGROUND: Optimal use of tricyclic antidepressants (TCAs) requires serum monitoring to determine if the appropriate therapeutic range has been attained and to assess possible side effects. This study was to evaluate the resolution capacity of the following four mobile phases which were previously reported; mobile phase I (methanol, acetonitrile and 5 mmol/L Na2HPO4: 41/15/44 by volume), II (methanol, acetonitrile and 5 mmol/L Na2HPO4,: 15/60/25 by volume), III (acetonitrile and 2-propanol: 95/5 by volume) and IV (methanol and n-butylamine: 99.5/0.5 by volume). METHODS: Amitriptyline (AT), nortriptyline (NT), imipramine (IMI) and doxepin (DOX) were used for the selection of appropriate mobile phase in high performance liquid chromatographic (HPLC) determination. TCAs were extracted from serum with hexane, isoamyl alcohol (99:1). The drug was re-extracted into 0.1 N HCl and an aliquot was injected into the HPLC. The analytical column was C-18 reversed phase column (3.9 mm x 30 cm; Waters, USA) with the flow rate of 1.5 mL/min. The UV detector signal was monitored at 254 nm. RESULTS: Mobile phase I disclosed 9.8-15.8 retention time (min), 5.1-8.8 capacity ratio and 1.0-2.2 resolution factors for the above four TCAs. Precision studies using this mobile phase demonstrated a coefficient variation of 2.4-4.7% in the concentration range of 500-125 ng/mL. Analytical recovery of AT and IMI was 85-90% at a concentration of 125 ng/mL and 250 ng/mL. CONCLUSIONS: Mobile phase I provided a reliable and excellent resolution of TCAs in the use of HPLC with the C-18 reversed phase column and UV absorbance detector.
2-Propanol ; Amitriptyline ; Antidepressive Agents, Tricyclic* ; Chromatography, High Pressure Liquid ; Doxepin ; Imipramine ; Nortriptyline

To study the effect of alpha1-acid glycoprotein 1 (ORM1) polymorphism on the concentration of free nortriptyline in serum, genotyping analysis was employed in ORM1 by sequencing. Eighteen unrelated male adults were chosen and given a single dose of 25 mg nortriptyline orally, then the blood samples were taken at 0, 1, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96 and 168 hours after drug administration. Nortriptyline and 10-OH-nortriptyline in serum and ultrafiltrate were detected for the total and free concentration by using HPLC-MS/MS. Pharmacokinetic parameters were compared among different ORM1 genotypes. No significant differences were shown in the pharmacokinetic parameters of total nortriptyline and 10-OH-nortriptyline. The mean AUC(0-infinity) of free nortritpyline in ORM1 * F/ * F1 subjects was significantly higher than that in ORM1 * F1/ * S and ORM1 * S/ * S subjects [(119.1 +/- 74.4) ng x mL(-1) x h vs (51.4 +/- 23.2) ng x mL(-1) x h and (42.4 +/- 11.6) ng x mL(-1) x h]. The percentage of protein binding in subjects with ORM1 * F1/ * F1 genotype at 2, 3, 4, 6, 8 and 12 h after administration was slightly lower than in those with ORM1 * F1/ * S and ORM1 * S/ * S genotypes while the distinct difference was shown at 4 h (P < 0.05). Different ORM1 genotypes might affect the protein binding percentage and the concentration of serum free nortriptyline. The ability binding to the drug was higher in subjects with ORM1 * S/ * S genotype than in those with other two genotypes, so as to cause the lower concentration of free nortriptyline.
Adult ; Area Under Curve ; Genotype ; Humans ; Male ; Nortriptyline ; analogs & derivatives ; blood ; pharmacokinetics ; Orosomucoid ; genetics ; metabolism ; Polymorphism, Genetic ; Protein Binding

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most serious complications associated with anticancer drugs. CIPN leads to a lower quality of life and dysfunction of the sensory, motor, and autonomic systems, and often causes patients to discontinue chemotherapy. It is usually misdiagnosed and undertreated due to a lack of consensus and unclear pathophysiology, for which many mechanisms have been suggested, including mitochondrial dysfunction, various pain mediators, abnormal spontaneous discharge in A and C fibers, and others. To date, no agents have been shown to effectively prevent CIPN, leading to debate as to the standard protocol. Duloxetine has demonstrated a moderate therapeutic effect against CIPN. Although tricyclic antidepressants (such as nortriptyline or desipramine), gabapentin, and a topical gel containing baclofen (10 mg), amitriptyline HCL (40 mg), and ketamine (20 mg) showed inconclusive results in CIPN trials, these agents are currently considered the best options for CIPN treatment. Therefore, further studies on the pathophysiology and treatment of CIPN are needed.
Amitriptyline ; Antidepressive Agents, Tricyclic ; Baclofen ; Consensus ; Drug Therapy* ; Humans ; Ketamine ; Nerve Fibers, Unmyelinated ; Neuralgia* ; Nortriptyline ; Peripheral Nervous System Diseases ; Quality of Life ; Duloxetine Hydrochloride

Chemotherapy induced peripheral neuropathy (CIPN) could debilitate the quality of life in the patients with cancer. According to the severity of CIPN, the modification of dosage of chemotherapeutic agents and switch to other drugs can be unavoidable. Platinum such as cisplatin and oxalipatin, vinka alkaloids, bortezomib, and taxane can cause CIPN. The characteristics and severity of CIPN depends on the dosages, duration of exposure of chemotherapeutic agents, comcomittant illness or other drugs affecting on peripheral nervous system and the methods of assessment for CIPN. The symptoms may last for several months or permanently even after quitting chemotherapy. Typically it distributed bilaterally and starts from the distal part of extremities and is presented progressively in stocking and glove pattern. Sensory nerve is more involved rather than motor nerve and amplitude of sensory nerve conduction is observed in CIPN. Prevention for CIPN is not effective at present. Tricyclic antidepressant including amitriptyline or nortriptyline and gabapentine have been tried in the practice for the management of CIPN despite of the lack of significant evidence through clinical trials. Recently duloxetine has been reported to decrease pain in the patients with CIPN compared with the patients with placebo (p = 0.03).
Alkaloids ; Amitriptyline ; Cisplatin ; Drug Therapy ; Extremities ; Humans ; Neural Conduction ; Nortriptyline ; Peripheral Nervous System ; Peripheral Nervous System Diseases* ; Platinum ; Quality of Life ; Bortezomib ; Duloxetine Hydrochloride

We present a case with decreased metabolic activity of CYP2D6, a cytochrome P450 enzyme catalyzing the metabolism of nortriptyline (NT). Conventional dosage regimen led to toxic plasma concentration of NT and adverse effects such as dry mouth, constipation, and dizziness in this case with genotype CYP2D6*5/*10B. This case suggests the clinical usefulness of pharmacogenetic testing in individualized dosage adjustments of NT.
Antidepressive Agents, Tricyclic/*adverse effects/pharmacokinetics ; Cytochrome P-450 CYP2D6/*genetics/metabolism ; Depression/*drug therapy/genetics ; Genotype ; Humans ; Male ; Middle Aged ; Nortriptyline/*adverse effects/pharmacokinetics