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@#Introduction: Smoking is associated with a higher risk of mortality, especially in smokers with cardiovascular and respiratory diseases. Smoking cessation remains the most effective approach in reducing smoking-related illness risks at all ages. For elderly smokers, smoking cessation has been proved to prolong life expectancy and reduce the risk of stroke and ischemic heart disease. However, a wide selection of smoking cessation medications makes prescribing challenging, especially among elderly smokers. Inability to recommend the best treatment may reduce the smoking cessation success rate in the elderly. Therefore, this study compares the effectiveness of pharmacotherapy available and correlate the effect of ageing on the effectiveness, leading to the recommendation of the best medication for elderly smokers. Method: A systematic searching strategy was performed in three different databases by using predetermined search strings. Results: Overall, this systematic review revealed that varenicline showed the greatest smoking cessation rate among the elderly, followed by bupropion and NRT. Conclusion: It is suggested that varenicline offered the best medical aid for smoking cessation in the elderly.
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A Simple, rapid, specific, accurate, economical and precise UV spectrophotometric and RP-HPLC methods (inaccordance with ICH guidelines) were developed and validated for determination of Nortriptyline hydrochlorideand Pregabalin in tablet dosage form. The first method was based on Q - absorbance ratio, and absorbances ofboth drugs were determined at 239 nm (λmax of Nortriptyline Hydrochloride) and 235 nm (Iso-absorptive Point)when dissolved in methanol. It is found that Pregabalin does not have chromophoric group. To be UV-sensitive,it was compulsory to introduce chromophoric group in Pregabalin structure and make it UV-sensitive. This wasachieved by converting the primary amine group of Pregabalin through reaction with benzoyl chloride to formbenzoylated derivative of Pregabalin. Benzoylated Pregabalin was determined at 225 nm using UV-visiblespectrophotometer. The second method was based on RP-HPLC. The chromatographic separation was performedon an Inertsil ODS C18 column (250 x 4.6mmx 5 μm) with a mobile phase of 0.56 %w/v Sodium hexane sulphonicacid dissolved in water acetonitrile (50:50 %v/v, pH 4.5 adjusted with Glacial Acetic Acid) at flow rate of 1.0mL/min with DAD detection wavelength at 210 nm. Retention times of Nortriptyline Hydrochloride andPregabalin were 7.3894 min and 4.0506 min, respectively. Beer-Lambert’s law obeyed the concentration rangeof 2-12 μg/mL for Nortriptyline Hydrochloride and 10-60 μg/mL for Pregabalin. The results indicated that bothspectrophotometric and RP-HPLC methods were linear, accurate, precise and robust with RSD values less than0.2% and % recovery was within the standard limits (99 - 102%).
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Background: The efficacy and safety of Pregabalin and Nortriptyline have been proved individually in low backache with radicular pain. However, there are limited number of studies comparing the efficacy of Pregabalin and Nortriptyline in Chronic Low Backache (CLBA) with radicular pain. Hence the present study was designed to determine the efficacy as well as tolerability of Pregabalin in comparison with that of Nortriptyline for reduction of pain in CLBA. The present study was an open label prospective observational study.Methods: Patients with CLBA, 15-60 years of age without specific cause and significant neurological deficit were included in the study. Severity of pain was assessed by Visual Analogue Scale (VAS). Patients were followed up at 2 and 4 weeks and their VAS scores and side effects were noted.Results: Both Pregabalin and Nortriptyline were effective in reducing pain, from baseline to 2 weeks and up to 4 weeks of treatment in chronic low backache with radicular pain, but there was no statistically significant difference between the two treatment groups. The incidences of side effects were less in the Nortriptyline treatment group as compared to Pregabalin.Conclusions: From the results of the present study it can be concluded that both Pregabalin and Nortriptyline were equally effective in the treatment of chronic low backache with radicular pain, but the incidence of adverse effects were more with Pregabalin as compared to Nortriptyline.
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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.
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Coronary Vessels , Muscle, Smooth , Myocytes, Smooth Muscle , Nortriptyline , SerotoninABSTRACT
Objective: To establish a determination method for the related substances in nortriptyline hydrochloride by HPLC. Methods:An Agilent C18 (250 mm × 4. 6 mm,5 μm) column was adopted with a mobile phase consisting of acetonitrile-0. 2% trieth-ylamine(pH 3. 0)(34 ∶66). The flow rate was 1. 0 ml·min-1, the detection wavelength was set at 210 nm, the column temperature was 40℃ and the injection volume was 20 μl. Results:The resolutions of the related substances were acceptable. The detection limit and the quantitation limit of the samples was 0. 40 ng and 1. 35 ng, respectively. Conclusion: The method is sensitive, accurate and specific, and can be used to determine the related substances in nortriptyline hydrochloride.
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Objective: To study the pharmacokinetics and brain/plasma concentration ratio of nortriptyline at multiple doses in mice which were pre-treated with physiological saline, piperine and verapamil. Methods: A total of 216 male Kun Ming mice[(25±3) g] were equally divided into 4 groups randomly. Each group was intragastrically administered physiological saline (B), piperine (170 μg/kg), piperine (5 mg/kg) and verapamil (5 mg/kg) for 8 days. On the 8th day, 1 h atfer giving the above drugs, each mice was intraperitoneally injected nortriptyline (13 mg/kg). The mice were sacriifced by picking off eyeballs at the time intervals of 5, 15, 30 min, and 1, 2, 4, 6, 8 and 12 h, andthe cerebra were collected and weighted. Nortriptyline in mouse plasma and brain was determined by HPLC-MS/MS. The pharmacokinetic properties of the plasma, brain and brain/plasma were calculated. Results: hTe AUC0-12 h of brain/plasma concentration ratio in the 170 μg/kg piperine group was significantly lower than that in the other groups (P<0.05), while the AUC0-12 h of brain/plasma concentration ratios in the 5 mg/kg piperine group and the verapamil group were not signiifcantly different from those of untreated mice. Conclusion: Piperine (170 μg/kg) may induce P-glycoprotein expression in the blood-brain barrier, while piperines at 5 mg/kg has no influence on P-glycoprotein expression in the blood-brain barrier.
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Background: Prisoners endure some of the worst health outcomes of any population group in the community. Smoking rates among prisoners remain high despite a significant reduction in smoking rates among the general public. This protocol describes a study in which we will assess the effectiveness of a smoking cessation intervention conducted among male prisoners. Methods/Design: 425 male smoking prisoners will be recruited. After completion of a baseline assessment, participants will receive a multi-component smoking cessation intervention comprising two half hour individual sessions of cognitive behavioural therapy and nicotine replacement therapy with either active Nortriptyline or placebo. Blinded follow up assessments will be conducted at 3, 6 and 12 months. Discussion: This study will provide data on the efficacy of Nortriptyline as a smoking cessation aid for male prisoners in combination with a multi-component smoking cessation intervention. No other smoking cessation randomised controlled trials on male prisoners has been published. Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR) identifier: #12606000229572. http://www.anzctr.org.au/trial_view.aspx?ID=1329.
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Physiology of vascular system in designing therapeutics is yet in its infancy. Co–Morbid conditions like depression and hypertension are complex physiological and pathological situations where PBPK drug interactions are highly probable due to change in systemic blood pressure resulting in organ perfusion that is an important determinant of drug dispersion. To generate evidence in support of this probability, a single 100 mg dose of Amitriptyline an object drug was administered with 10 mg of Amlodipine as a precipitating drug in an open label, randomized parallel group, controlled clinical study based on PK/PD analysis model. Hypertensive patients with depression test group (TI), Hypertensive patients with out depression, test group (TII), Normotensive patients with depression, control group (CI) and Normal healthy volunteers, control group (CII), having 25 participants each were enrolled in this study. Plasma samples after single dose Amitriptyline at 0, 1, 2, 4, 8, 12, 24 hours were drawn along with measurement of heart rate, respiratory rate and blood pressure. A wash out period of 7 days for the two test groups (TI and TII) was given. Amlodipine 10 mg was administered which lowered the DBP by nearly 5 to 10 mm Hg, when the Amitriptyline was administered orally and the plasma samples were drawn for PK analysis along with PD parameters in a designed time event profile. Estimation of Amitriptyline and its metabolite Nortriptyline was performed by HPLC. Pharmacokinetic parameters were calculated using a non-compartmental model. After Amlodipine induced fall in DBP in both test groups, T1/2, C max, T max, CLT, AUC of Amitriptyline and Nortriptyline changed in both the test groups (TI and TII).
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OBJECTIVE: To evaluate the effectiveness of nicotine replacement therapy (NRT), bupropion, nortriptyline and combination therapy and describe factors associated with treatment success. INTRODUCTION: Clinical trials clearly demonstrate the efficacy of pharmacotherapy in smoking cessation. However, it is only after its use in real-life settings that clinical effectiveness and limitations of a treatment are fully known. METHODS: Patients attended a four-session cognitive-behavioral program and received medicines free of charge. Abstinence from smoking was assessed at each visit. RESULTS: A total of 868 smokers (68.8 percent women) were included. Their mean age was 49.6 years; the amount smoked was 25 cigarettes/day and the Fagerströ m Score was 6.6. Abstinence rates after 6 months and 1 year were 36.5 percent and 33.6 percent. In univariate analysis, male gender, age (>50), higher number of cigarettes smoked, cardiovascular comorbidities, longer interval from the last cigarette and combined treatment of nortriptyline plus NRT were predictive of abstinence, while neuropsychiatric comorbidities and the answer ''yes'' to the question ''Do you smoke more often during the first hours after waking'' were correlated with failure. In a multivariate model, predictors of abstinence were neuropsychiatric comorbidities, the answer ''yes'' to the question ''Do you smoke more often during the first hours after waking'' and combined treatment of nortriptyline plus NRT. Male gender and a longer period from the last cigarette were correlated with lower abstinence rate. CONCLUSION: Satisfactory success rates were obtained in a teaching hospital. Factors such as age, daily cigarette consumption, number of pack-years and dependency score were not reliable markers of abstinence. The combination nortriptyline+NRT was independently associated with higher abstinence rates.
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Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Smoking Cessation/methods , Smoking/drug therapy , Age Factors , Bupropion/therapeutic use , Combined Modality Therapy , Follow-Up Studies , Multivariate Analysis , Nicotine/therapeutic use , Nortriptyline/therapeutic use , Retrospective Studies , Sex Factors , Time Factors , Treatment OutcomeABSTRACT
Huntington's disease (HD) is an autosomal dominant neurodegenerative disease. A cardinal histopathologic feature of HD is the progressive loss of striatal medium spiny neurons. As there is no effective treatment for this fatal disease so far, we explore the therapeutic potential of nortriptyline to identify drugs that might be effective treatments for HD. N548mu [ 1955-128] huntingtin stable ST14A cell line was cultured and incubated in the presence or absence of serial concentrations of nortriptyline. Then R6/2 transgenic HD mice were treated with nortriptyline from five to twenty-one weeks of age. Nortriptyline protected striatal cells expressing mutant huntingtin when shifted to a nonpermissive temperature. Nortriptyline delay the disease onset to 127 d in R6/2 mice as compared with 102 d in saline-treated controls, but nortriptyline did not significantly delay mortality. As a gross marker of lack of systemic toxicity, there was no significant difference in the weight of the treated and control R6/2 mice. The results demonstrate that clinically reasonable doses of one of the identified drugs, nortriptyline, delays disease onset in a mouse model of the disease more than any previously identified compound. The most desirable features of a drug for HD are minimal toxicity and the ability to extend symptom-free living. Nortriptyline appears to be one such good candidate.
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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.
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Humans , Male , Middle Aged , Antidepressive Agents, Tricyclic/adverse effects , Cytochrome P-450 CYP2D6/genetics , Depression/drug therapy , Genotype , Nortriptyline/adverse effectsABSTRACT
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.
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Humans , Amitriptyline , Depression , Fluoxetine , Inpatients , Nortriptyline , Outpatients , PlasmaABSTRACT
AIM To develop a sensitive, specific and reliable reversed phase high performance liquid chromatographic method(RP\|HPLC) to determine the total and unbound(free) concentrations in human plasma of amitriptyline and its major metabolite, nortriptyline. METHODS\ The assay involved a simple extraction procedure. The mobile phase consisted of acetonitrile and distilled water(30∶70, V/V ), containing triethylamine(0 5%) and orthophosphoric acid(0 3%), pH 3 1. Separation was achieved on the C18 ODS column and the effluent was measured for UV absorption at 240 nm. RESULTS The calibration curves were linear in the range of 4～400 ?g?L -1 for total concentration, and in the range of 4～64 ?g?L -1 for free concentration for both amitriptyline and nortriptyline. The lowest limits of detection were 4 ?g?L -1 for both compounds. The absolute recovery rates were 102 0%?3 77% for amitriptyline and 99 3%?7 13% for nortriptyline. The precision values(RSD) of intra day and inter day for both amitriptyline and for nortriptyline were determined to be