Am J Phys Med Rehabil. 1992 Oct;71(5):279-82.
Lack of effect of amitriptyline in murine myotonia.

Carter GT, Longley KJ, Walsh SA, Entrikin RK.

Department of Physical Medicine and Rehabilitation, University of California, Davis.

Amitriptyline, a tricyclic antidepressant, has been reported to diminish signs of human myotonic muscular dystrophy, but has not been examined in other myotonias. Normal and myotonic (ADRmto) mice were injected acutely with either amitriptyline, phenytoin, procainamide or 0.9% saline. In addition, two groups of myotonic mice were injected chronically with either 0.9% saline or amitriptyline for 28 days. Behavior, assessed before injection using a "drop test," was re-evaluated at 30-min intervals for up to 180 min postinjection, as well as at the end of the 28-day chronic trial. If improvement in behavior was noted, the mice were then evaluated with insertional needle electromyography (EMG) and in vitro contractility (maximal tetanic tension and relaxation time) studies. Neither acute nor chronic amitriptyline administration had any beneficial effect on behavior, EMG or contractile parameters in myotonic mice. Phenytoin abolished abnormal EMG activity and improved behavior. Procainamide improved behavior and contractility parameters but had no effect on EMG. These results confirm that the myotonic mouse is responsive to classic antimyotonic agents, but not to amitriptyline.

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J Chromatogr. 1992 Jul 24;578(2):273-82.
Column switching and high-performance liquid chromatography in the analysis of amitriptyline, nortriptyline and hydroxylated metabolites in human plasma or serum.

Hartter S, Hiemke C.

Department of Psychiatry, University of Mainz, Germany.

A column-switching system for the direct injection of plasma or serum samples, followed by isocratic high-performance liquid chromatography and ultraviolet detection, is described for the simultaneous quantitation of the tricyclic antidepressant amitriptyline, its demethylated metabolite nortriptyline and the E- and Z-isomers of 10-hydroxy amitriptyline and 10-hydroxynortriptyline. The method included adsorption of amitriptyline and metabolites on a reversed-phase C8 clean-up column (10 microns; 20 mm x 4.6 mm I.D.), washing of unwanted material to waste and, after on-line column-switching, separation on a cyanopropyl analytical column (5 microns; 250 mm x 4.6 mm I.D.). The compounds of interest were separated and eluted using acetonitrile-methanol-0.01 M phosphate buffer (pH 6.8) (578:188:235, v/v) within less than 20 min. Various drugs frequently co-administered with amitriptyline or other antidepressants did not interfere with the determinations. In plasma samples spiked with 25-300 ng/ml, the recoveries were between 84 and 112% and the inter-assay coefficients of variation were 3-11%. After a minor modification, as little as 5 ng/ml could be quantitated. There were linear correlations (r greater than 0.99) between drug concentrations of 5-500 ng/ml and the detector signal. The method allows routine measurements of amitriptyline, nortriptyline and hydroxylated metabolites in blood plasma or serum of patients treated with amitriptyline or nortriptyline, and enables the results to be reported within 1 h.

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Eur J Pharmacol. 1988 Nov 15;157(1):51-60.
Non-selectivity of amitriptyline for subtypes of brain muscarinic receptors demonstrated in binding and functional assays.

McKinney M, Lee NH, Anderson DJ, Vella-Rountree L, el-Fakahany EE.

Department 47U, Abbott Laboratories, North Chicago, IL 60064.

The characteristics of interaction of amitriptyline, a tricyclic antidepressant, with rat brain muscarinic receptors were assessed using both radioligand binding and functional assays. In competition studies, amitriptyline displaced muscarinic ligand binding from a single high-affinity site in homogenates of various brain regions which have a different distribution of M1 and M2 receptor subtypes. The affinity of amitriptyline for muscarinic receptors was also comparable in all brain regions. Furthermore, amitriptyline identified a single species of muscarinic receptors in intact cells dissociated from the cerebral cortex and in cerebrocortical slices. The non-selectivity of amitriptyline for muscarinic receptor subtypes in these preparations was in contrast to the selectivity exhibited by pirenzepine. This non-selective nature of amitriptyline was also evident in functional assays, since this antidepressant was equipotent at antagonizing M1-mediated increase in phosphoinositide hydrolysis and M2-mediated inhibition of cyclic AMP formation in dissociated cortical cells. Atropine was also equipotent at blocking both responses but was 20- to 30-fold more potent than amitriptyline. These results demonstrate that amitriptyline behaves as a non-selective muscarinic antagonist using both radioligand binding and functional measurements.

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Br J Gen Pract. 1992 Jun;42(359):244-6.
Acute herpes zoster and postherpetic neuralgia: effects of acyclovir and outcome of treatment with amitriptyline.

Bowsher D.

Pain Research Institute, Liverpool.

This retrospective study was designed to assess the effects of acyclovir treatment of acute herpes zoster on subsequent postherpetic neuralgia, and to examine the effects of amitriptyline in the treatment of postherpetic neuralgia. Eighty seven patients with postherpetic neuralgia of three or more months' duration were studied: 24 of them had had their herpes zoster treated with oral acyclovir. At first presentation, only 25% of the 24 patients who had had their herpes zoster treated with acyclovir selected the word group containing burning on the McGill pain questionnaire compared with 76% of the 63 patients who had not received acyclovir. A higher proportion of patients who had had acyclovir than had not selected the word group which contains the word aching (63% versus 49%). Acyclovir thus appears to change the nature of postherpetic neuralgia. Postherpetic neuralgia was treated with amitriptyline, alone or in combination with distigmine and/or sodium valproate. There was a strong correlation between pain relief and the interval between the occurrence of herpes zoster and the initiation of treatment with amitriptyline--early treatment is almost twice as likely to be successful as late. Since conventional analgesics and sympatholytic drugs are of no benefit in the treatment of established postherpetic neuralgia, the sequelae of herpes zoster must, therefore, be recognized and treated with amitriptyline as soon as possible.

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Clin Pharmacol Ther. 1992 Oct;52(4):350-8.
Enantioselective amitriptyline metabolism in patients phenotyped for two cytochrome P450 isozymes.

Breyer-Pfaff U, Pfandl B, Nill K, Nusser E, Monney C, Jonzier-Perey M, Baettig D, Baumann P.

Institut fur Toxikologie, Universitat Tubingen, Germany.

In 26 hospitalized patients with depression, a combined pharmacogenetic test with dextromethorphan, a substrate of cytochrome P450IID6, and mephenytoin, the S-form of which is hydroxylated by a P450IIC isozyme, was carried out before amitriptyline therapy. Metabolites were determined in 24-hour urine samples collected on treatment day 8, and the contributions of individual compounds, including the four isomers of 10-hydroxy amitriptyline and 10-hydroxynortriptyline to total excretion were calculated. Formation of (-)-E-10-hydroxy amitriptyline and (-)-E-10-hydroxynortriptyline apparently depends on the activity of cytochrome P450IID6 because negative correlations existed between the log metabolic ratio of dextromethorphan and the relative quantities of these enantiomers. In contrast, correlations were positive for nortriptyline, (+)-E-10-hydroxynortriptyline, (-)-Z-10-hydroxynortriptyline, and (+)-Z-10-hydroxynortriptyline. The mephenytoin hydroxylase seems to participate in side-chain demethylation to the secondary and primary amines, because the log metabolic ratio of mephenytoin correlated negatively with the relative quantity of E-10-hydroxydidesmethylamitriptyline and positively with that of amitriptyline and its N-glucuronide.

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med.uni-jena.de

INTRODUCTION: A double-blind, randomized phase-III study was conducted with the aim to compare the efficacy and safety of venlafaxine ER (extended release) with that of amitriptyline ER in moderately depressed outpatients. METHODS: Patients with major depression of moderate severity, HAM-D (Hamilton Depression scale, 21 items) score 20-26, were given a six-week double-blind treatment with venlafaxine ER and amitriptyline ER in a dosis of 75 mg each, which could be increased to 150 mg, if necessary. Efficacy was assessed using HAM-D and CGI (clinical global impression) scores. Safety analysis was carried out using the HAM-D item 3 to assess suicidality, the d2 test to evaluate attention and drug screening for benzodiazepines. Adverse events were recorded at each visit. RESULTS: 160 patients were randomized. There were 151 patients available for analysis in the intent-to-treat (ITT) population. The according-to-protocol (ATP) population consisted of 117 patients, with 60 patients in the venlafaxine ER group and 57 in the amitriptyline ER (extended release) group. The non-inferiority of venlafaxine ER compared to amitriptyline ER with reference to the primary efficacy parameter, the change of HAM-D total score, could be proven in both the ITT population and the ATP population. There were no significant differences between groups in the HAM-D response rates and the CGI scores of items 1 (severity) and 2 (improvement). Venlafaxine ER showed a more favorable safety profile than amitriptyline ER: adverse drug reactions were less frequent under venlafaxine ER than under amitriptyline ER. Most of the discontinuations in the amitriptyline ER group were due to dry mouth. The d2 test showed greater improvement of performance under venlafaxine ER. DISCUSSION: In this study with patients treated for major depression of moderate severity, the non-inferiority of venlafaxine ER compared to amitriptyline ER with respect to the chosen efficacy parameter could be demonstrated. Venlafaxine ER showed a more favorable safety profile than amitriptyline ER.

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centras.lt

The problem of acute intoxication has become very urgent now due to a great number of various chemical preparations accumulated during the last decades in the environment. Intoxications with psychotropic drugs and their mixtures form the significant part of the intoxications; there is an increasing tendency of intoxication with several preparations at a time. Amitriptyline and codeine are the preparations, which more frequently can cause intoxication. Fluoxetine is one of the newest and often used antidepressants. Under certain circumstances, like overdose, using all preparations together, long term using or using for suicide, these preparations can be even a cause of death. In such cases amitriptyline, fluoxetine and codeine become the objects of chemical-toxicological analysis. The possibility of the separation and identification of amitriptyline, fluoxetine and codeine in the mixture using thin-layer chromatography was established. Dragendorf reagent, modified by Munje, is most suitable for the spray-distinct of the chromatographic plates for all three substances. Amitriptyline research limit, using this developer, is 0.4 micro g, fluoxetine - 1.6 micro g, codeine - 0.8 micro g. Most acceptable for separation the components of the mixture are 5 mobile phases: 1. Diethyl acetate-methanol-ammonium hydroxide (concentrated solution) (85:10:5). Amitriptyline, fluoxetine and codeine R(f) medium values respectively are 0.94; 0.63; 0.51. 2. Buthylacetate-methanol-ammonium hydroxide (concentrated solution) (85:10:5). Amitriptyline, fluoxetine and codeine R(f) medium values respectively are 0.65; 0.24; 0.15. 3. Cyclohexane-diethyl acetate-diethyl amine (70:15:15). Amitriptyline, fluoxetine and codeine R(f) medium values respectively are 0.93; 0.75; 0.37. 4. Cyclohexane-buthylacetate-diethyl amine (70:15:15). Amitriptyline, fluoxetine and codeine R(f) medium values respectively are 0.92; 0.51; 0.25. 5. Acetone-1,4-dioxane-ammonium hydroxide (concentrated solution) (30:68:2). Amitriptyline, fluoxetine and codeine R(f) medium values respectively are 0.82; 0.62; 0.42. Recommended methodology for the separation and identification of amitriptyline, fluoxetine and codeine in the mixture using thin-layer chromatography is statistically reliable: when confidence level is 0.95, relative error is less than 0.05; standard deviation is from 0.007 to 0.03. Recommended methodology suits for mixture, extracted from biological liquids, components separation and identification.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14617874&dopt=Abstract Elavil amitriptyline[PubMed - in process]