Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new amitriptyline research articles will be listed here shortly after becoming available to us.
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Medical research on amitriptyline
NMR characterization of the host-guest inclusion complex between beta-cyclodextrin and doxepin.
Magn Reson Chem. 2008 Jul 9;
Cruz JR, Becker BA, Morris KF, Larive CK
The interaction between doxepin, a member of the tricyclic antidepressant (TCA) class of drugs, with beta-cyclodextrin (beta-CD) was investigated using NMR. Several TCAs have been reported to form a complex with beta-CD having 1:1 stoichiometry. Previous results from UV-visible spectroscopy, fluorescence measurements, and molecular modeling indicated that for imipramine, desipramine, and amitriptyline, the TCA aliphatic tail is included in the cyclodextrin cavity with apparently no interaction of the tricyclic ring. An alternative view of the doxepin-beta-CD complex is presented in this work using analysis of complexation-induced chemical shifts (CICSs), the method of continuous variation (Job's analysis), and analysis of ROESY spectra. The Job's plot derived from the NMR spectral data confirms that the complex formed has 1:1 stoichiometry. The largest changes in the CICS data were observed for the aromatic protons of one of the doxepin rings, with much smaller chemical shift changes observed for the protons of the other aromatic ring and the doxepin tail. Perhaps the most significant evidence for inclusion of the doxepin tricyclic ring is the strong ROESY cross peaks between the doxepin aromatic resonances and the protons located inside the beta-CD cavity. Changes in the doxepin (1)H NMR spectrum and the behavior of ROESY exchange cross peaks suggest that inclusion complex formation decreases the rate of internal motions of doxepin. Copyright (c) 2008 John Wiley & Sons, Ltd.
Clin Toxicol (Phila). 2008 Jun 16; 1-9
Akgun A, Kalkan S, Hocaoglu N, Gidener S, Tuncok Y
Objective. We investigated the effects of adenosine receptor antagonists on amitriptyline-induced cardiotoxicity in isolated rat hearts. Methods. The amitriptyline concentrations that prolonged the QRS duration more than 150% (10(-4) M) and 50-75% (5.5 x 10(-5) M) were accepted as the control groups for two experimental protocols, respectively. In the first protocol, amitriptyline (10(-4) M) was infused following pretreatment with a selective adenosine A(1) receptor antagonist, DPCPX (8-cyclopentyl-1,3-Dipropylxanthine,10(-4) to 10(-6) M) or a selective adenosine A(2a) receptor antagonist, CSC (8-3-chlorostyryl-caffeine,10(-4) to 10(-6) M). In the second protocol, amitriptyline (5.5 x 10(-5) M) was infused following pretreatment with DPCPX (10(-4) M) or CSC (10(-5) M). Left ventricular developed pressure (LVDP), dp/dt(max), QRS duration and heart rate (HR) were measured. Results. In the first protocol, 10(-4) M DPCPX pretreatment shortened QRS duration at 50 minutes when compared to the control group (p < 0.05). In the second protocol, pretreatment with 10(-4) M DPCPX shortened the QRS duration at 40, 50, and 60 minutes after amitriptyline infusion when compared to the control group (p < 0.05, p < 0.01 and p < 0.05, respectively). Pretreatment with 10(-5) M CSC prolonged QRS duration at 20, 30, and 60 minutes (p < 0.05). Amitriptyline infusion following pretreatment with DPCPX or CSC did not change LVDP, dp/dt(max,) or HR when compared to control in both protocols (p > 0.05). Conclusion. While 10(-4) M DPCPX shortened QRS prolongation, 10(-5) M CSC prolonged QRS duration in the isolated rat hearts with prolonged QRS duration induced by 5.5 x 10(-5)M amitriptyline. An adenosine A(1) receptor antagonist, DPCPX, might shorten amitriptyline-induced QRS prolongation by activating beta adrenergic receptors.
J Pharm Biomed Anal. 2008 May 28;
de Castro A, Concheiro M, Quintela O, Cruz A, López-Rivadulla M
In this paper, a fast, sensitive and selective LC-MS/MS method is described for the simultaneous determination of amitriptyline, imipramine, clomipramine, fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram and venlafaxine, as well as some of their main metabolites (nortriptyline, desipramine, norclomipramine and norfluoxetine), in oral fluid and plasma. The sample (0.2mL) was extracted with an automated solid-phase extraction system (ASPEC XL), using mixed mode OASIS MCX cartridges. Chromatographic separation was performed in a Sunfire C18 IS column (20mmx2.1mm, 3.5mum), using a gradient of acetonitrile and ammonium formate (pH 3; 2mM) as mobile phase, which allowed the elution of all the compounds in less than 5min. The method has been fully validated in both specimens. This method was initially applied to the analysis of oral fluid and plasma samples from patients on antidepressant treatment in order to assess for which compounds it was likely to find a good correlation between both matrices. The best results were obtained for venlafaxine, so the study was extended for this compound, comparing the ratio between oral fluid and plasma concentrations (R(OF/PL)) in five patients on venlafaxine treatment when both samples were collected simultaneously on four different occasions. An important inter and intraindividual variability was found in oral fluid concentrations for 150mg dose (mean=287.5ng/m, range 58.8-531.2ng/mL) and for 75mg dose (mean=186.3ng/mL, range=82.1-289.2ng/mL). R(OF/PL) was calculated for each patient on the four different occasions, showing also a high variability (CV=24.2-69.6%).
Studies on Somnolence in the Daytime Caused by Drugs Used for Neuropathic Pain.
J Pharmacol Sci. 2008 Jun 28;
Takeda Y, Ishida T, Tsutsui R, Toide K, Tanimoto-Mori S, Watanabe S, Kanai Y, Kamei C
In the present study, the characteristics of the sleep features of amitriptyline, mexiletine, and N-(4-tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropyradine-1(2H)-carbox-amide (BCTC) were studied. Electrodes were chronically implanted into the frontal cortex and the dorsal neck muscles of rats for electroencephalogram (EEG) and electromyogram (EMG) measurements, respectively. EEG and EMG were recorded with an electroencephalograph, and SleepSign ver. 2.0. was used for sleep-wake state analysis. Recordings were performed from 11:00 to 17:00. Amitriptyline caused significant decreases in sleep latency and total wake time and an increase in total non-rapid eye movement (non-REM) sleep time. Mexiletine caused a significant decrease in sleep latency, but no significant effect was observed in total wake time and total non-REM sleep time. On the other hand, BCTC, which is an antagonist of transient receptor potential vaniloid 1 (TRPV1), showed no significant effect on sleep latency, total wake time, total non-REM sleep time, and total REM sleep time. From these results, it can be concluded that a TRPV1 antagonist may become a useful drug for neuropathic pain without sedative side effects in the daytime, different from amitriptyline and mexiletine.
Am J Obstet Gynecol. 2008 Jul; 199(1): 71.e1-10
Stanford EJ, Chen A, Wan GJ, Lunacsek OE, Sand PK
OBJECTIVE: The aim of this study was to examine treatment modalities, health care resource utilization, and costs in patients diagnosed with interstitial cystitis (IC). STUDY DESIGN: Patients with a diagnosis of IC were identified from a national managed care administration claims database and classified into treatment cohorts. All-cause health care resource utilization and costs were calculated by treatment cohort. RESULTS: Patients treated with narcotics plus nonnarcotic analgesics were associated with higher mean health care costs. Patient cohorts treated with some of the more common oral therapies for interstitial cystitis, including pentosan polysulfate sodium, amitriptyline, and hydroxyzine, were associated with lower costs. Physician visits were fewest among patients treated with pentosan polysulfate sodium plus amitriptyline and hydroxyzine. Physician visits were higher for cohorts that included dimethyl sulfoxide plus cystoscopy or bladder irrigation, or narcotics plus nonnarcotic analgesics. CONCLUSION: Interstitial cystitis is associated with substantial costs and health care resource utilization.
Talanta. 2008 Jun 15; 75(5): 1293-9
Yazdi AS, Razavi N, Yazdinejad SR
Dispersive liquid-liquid microextraction (DLLME) coupled with gas chromatography-flame ionization detection (GC-FID) was applied for the determination of two tricyclic antidepressant drugs (TCAs), amitriptyline and nortriptyline, from water samples. This method is a very simple and rapid method for the extraction and preconcentration of these drugs from environmental sample solutions. In this method, the appropriate mixture of extraction solvent (18 microL Carbon tetrachloride) and disperser solvent (1 mL methanol) are injected rapidly into the aqueous sample (5.0 mL) by syringe. Therefore, cloudy solution is formed. In fact, it is consisted of fine particles of extraction solvent which is dispersed entirely into aqueous phase. The mixture was centrifuged and the extraction solvent is sedimented on the bottom of the conical test tube. 2.0 microL of the sedimented phase is injected into the GC for separation and determination of TCAs. Some important parameters, such as kind of extraction and disperser solvent and volume of them, extraction time, pH and ionic strength of the aqueous feed solution were optimized. Under the optimal conditions, the enrichment factors and extraction recoveries were between 740.04-1000.25 and 54.76-74.02%, respectively. The linear range was (0.005-16 microg mL(-1)) and limits of detection were between 0.005 and 0.01 microg mL(-1) for each of the analytes. The relative standard deviations (R.S.D.) for 4 microg mL(-1) of TCAs in water were in the range of 5.6-6.4 (n=6). The performance of the proposed technique was evaluated for determination of TCAs in blood plasma.
Zh Nevrol Psikhiatr Im S S Korsakova. 2008; 108(6): 43-46
Tarasova SV, Amelin AV, Skoromets AA
Efficacy of antidepressants fluvoxamine, amitriptyline and transcranial electrostimulation of the brain in the treatment of chronic daily headache has been studied. Amitriptyline had the highest effect in dosage 50 mg daily but was not well tolerated by patients that resulted in that only 50% of them finished the study. Fluvoxamine had high efficacy and good tolerability in the treatment of chronic daily headache and medication overuse headache. Small dosages of amitriptyline and fluvoxamine potentiated the analgesic effect of transcranial electrostimulation of the brain. The combination of antidepressants with transcranial electrostimulation of the brain alleviated the negative effect of the withdrawal of overused analgesics and may be recommended for out-patient use.
[Antidepressant drugs in the treatment of tension-type headache.]
Med Clin (Barc). 2008 May 24; 130(19): 751-7
Medina Ortiz O, Arango C, Ezpeleta D
Tension-type headache is the most common form of headache. Eighty percent of cases occur before 40 years of age. A wide variety of antidepressants have been used to treat it. Tricyclics are the only antidepressants that have demonstrated their effectiveness in treating chronic tension-type headache, amitriptyline being the drug of choice. Selective serotonin reuptake inhibitors and other families of antidepressants have not shown conclusive results yet. The present study is a review of the scientific evidence available on antidepressants for treatment of this kind of headache.
J Psychopharmacol. 2008 Jun 26;
van den Broek WW, Mulder PG, van Os E, Birkenhäger TK, Pluijms E, Bruijn JA
Abstract With respect to the pharmacological characteristic, venlafaxine is comparable with tricyclic antidepressants (TCAs), and venlafaxine might be comparable in efficacy. We performed a systematic review investigating the relative efficacy and tolerability of venlafaxine compared with TCAs (imipramine, clomipramine, amitriptyline, nortriptyline and desipramine). Relevant double-blind randomised trials were identified from systematic searches of electronic databases. An exact analysis of the estimated odds ratios of response of the TCA relative to venlafaxine showed no overall significance of treatment effect (P = 0.38). The odds ratios were not homogenous across studies (P = 0.0213). The average dose of venlafaxine was 103.5 mg/day and for the TCA 106.1 mg/day. An exact analysis of the estimated odds ratios of the withdrawals and side effects in the trials with a TCA relative to venlafaxine showed no overall significance of withdrawal. From our review, no significant difference in treatment effect between low dose of both venlafaxine and the TCAs could be found. In our opinion, because of the heterogeneity of the odds ratios, one cannot conclude that they are of equal efficacy.
Neurosci Lett. 2008 Aug 1; 440(2): 181-4
Sawynok J, Reid AR, Fredholm BB
Amitriptyline is used to treat neuropathic pain in humans. It produces antinociception in several animal models of pain, and this effect is blocked by methylxanthine adenosine receptor antagonists which implicates adenosine it its actions. Here, the antinociceptive effect of amitriptyline, and the ability of caffeine to reverse it, were examined using the formalin test (a model of persistent pain) in wild type mice and mice lacking the adenosine A(1) receptor (A1R). Amitriptyline produced dose-related suppression of flinching in wild type mice following both systemic and intraplantar drug administration; both of these effects were unaltered in A1R -/- mice. Following systemic administration, caffeine reversed the systemic effect of amitriptyline in wild type, but not A1R -/- mice; -/+ mice exhibited an intermediate effect. Intraplantar administration of caffeine also reversed the effect of intraplantar amitriptyline in A1R +/+, but not in -/- or +/- mice. These results indicate that adenosine A(1) receptors are not required in order for amitriptyline to cause antinociception in mice, but they are required to see caffeine reversal of this antinociceptive effect. When A1Rs are present, actions of amitriptyline may, however, partly depend on A1Rs.