Now-a-days, the occurrence of antidepressant residues in surface waters has become a major concern. Amitriptyline (AMI) has been described to treat depression and other disorders for decades. However, little is known about its effect on non-target organisms. The aim of this study was to assess the potential impact of AMI on the mRNA expression of antioxidant and detoxification enzymes during the early embryonic development of zebrafish (Danio rerio). Fertilized D. rerio embryos were exposed to AMI at concentrations of 300 ng/L and 30 μg/L and sampled 24, 48, 96, and 144 h post fertilization (hpf) to assess the mRNA expressions of cytochrome P450 1A1, glutathione-S-transferase, glutathione peroxidase, superoxide dismutase, and catalase. The time courses of the mRNA expressions of antioxidant and detoxification enzymes revealed characteristic changes during embryonic development causing generally transient changes post hatching; however, AMI did not cause any significant impact except in the case of CAT after 144 h, which was significantly upregulated by the AMI concentration of 30 μg/L. The results suggest that the antidepressant AMI causes only moderate to minor impacts on antioxidant and detoxification enzymes during early embryonic development of the non-target organism D. rerio and that CAT is the only biomarker affected by AMI.

• Keywords
• CAT, CYP1A, Fish, GPx, GST, SOD,
• MeSH
• Amitriptyline pharmacology   therapeutic use   MeSH
• Antidepressive Agents, Tricyclic pharmacology   therapeutic use   MeSH
• Antioxidants metabolism   MeSH
• Zebrafish MeSH
• Embryo, Nonmammalian drug effects   metabolism   MeSH
• Embryonic Development drug effects   MeSH
• RNA, Messenger metabolism   MeSH
• Oxidative Stress drug effects   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Amitriptyline MeSH
• Antidepressive Agents, Tricyclic MeSH
• Antioxidants MeSH
• RNA, Messenger MeSH

OBJECTIVE: Monoamine oxidase (MAO), the enzyme responsible for metabolism of monoamine neurotransmitters, has an important role in the brain development and function, and MAO inhibitors have a range of potential therapeutic uses. We investigated systematically in vitro effects of pharmacologically different antidepressants and mood stabilizers on MAO activity. METHODS: Effects of drugs on the activity of MAO were measured in crude mitochondrial fraction isolated from cortex of pig brain, when radiolabeled serotonin (for MAO-A) or phenylethylamine (for MAO-B) was used as substrate. The several antidepressants and mood stabilizers were compared with effects of well known MAO inhibitors such as moclobemide, iproniazid, pargyline, and clorgyline. RESULTS: In general, the effect of tested drugs was found to be inhibitory. The half maximal inhibitory concentration, parameters of enzyme kinetic, and mechanism of inhibition were determined. MAO-A was inhibited by the following drugs: pargyline > clorgyline > iproniazid > fluoxetine > desipramine > amitriptyline > imipramine > citalopram > venlafaxine > reboxetine > olanzapine > mirtazapine > tianeptine > moclobemide, cocaine >> lithium, valproate. MAO-B was inhibited by the following drugs: pargyline > clorgyline > iproniazid > fluoxetine > venlafaxine > amitriptyline > olanzapine > citalopram > desipramine > reboxetine > imipramine > tianeptine > mirtazapine, cocaine >> moclobemide, lithium, valproate. The mechanism of inhibition of MAOs by several antidepressants was found various. CONCLUSIONS: It was concluded that MAO activity is acutely affected by pharmacologically different antidepressants at relatively high drug concentrations; this effect is inhibitory. There are differences both in inhibitory potency and in mechanism of inhibition between both several drugs and the two MAO isoforms. While MAO inhibition is not primary biochemical effect related to their therapeutic action, it can be supposed that decrease of MAO activity may be concerned in some effects of these drugs on serotonergic, noradrenergic, and dopaminergic neurotransmission.

• MeSH
• Affect drug effects   MeSH
• Amitriptyline pharmacology   MeSH
• Antidepressive Agents pharmacology   MeSH
• Antimanic Agents pharmacology   MeSH
• Benzodiazepines pharmacology   MeSH
• Citalopram pharmacology   MeSH
• Cyclohexanols pharmacology   MeSH
• Desipramine pharmacology   MeSH
• Fluoxetine pharmacology   MeSH
• Imipramine pharmacology   MeSH
• Monoamine Oxidase Inhibitors pharmacology   MeSH
• Iproniazid pharmacology   MeSH
• Clorgyline pharmacology   MeSH
• Cocaine pharmacology   MeSH
• Valproic Acid pharmacology   MeSH
• Lithium pharmacology   MeSH
• Mianserin analogs & derivatives   pharmacology   MeSH
• Mirtazapine MeSH
• Mitochondria drug effects   enzymology   MeSH
• Moclobemide pharmacology   MeSH
• Monoamine Oxidase drug effects   metabolism   MeSH
• Morpholines pharmacology   MeSH
• Cerebral Cortex cytology   MeSH
• Olanzapine MeSH
• Pargyline pharmacology   MeSH
• Swine MeSH
• Reboxetine MeSH
• In Vitro Techniques MeSH
• Thiazepines pharmacology   MeSH
• Venlafaxine Hydrochloride MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Amitriptyline MeSH
• Antidepressive Agents MeSH
• Antimanic Agents MeSH
• Benzodiazepines MeSH
• Citalopram MeSH
• Cyclohexanols MeSH
• Desipramine MeSH
• Fluoxetine MeSH
• Imipramine MeSH
• Monoamine Oxidase Inhibitors MeSH
• Iproniazid MeSH
• Clorgyline MeSH
• Cocaine MeSH
• Valproic Acid MeSH
• Lithium MeSH
• Mianserin MeSH
• Mirtazapine MeSH
• Moclobemide MeSH
• Monoamine Oxidase MeSH
• Morpholines MeSH
• Olanzapine MeSH
• Pargyline MeSH
• Reboxetine MeSH
• Thiazepines MeSH
• tianeptine MeSH Browser
• Venlafaxine Hydrochloride MeSH

BACKGROUND: The increasing cost of pharmaceuticals in the Czech Republic has led to the restriction on prescriptions of expensive new antidepressants. The aim of the study was to compare the costs and outcomes of using amitriptyline, citalopram and fluoxetine in the treatment of major depression. METHODS: Ninety patients (69 women) with a mean age of 44.5 years (S.D. = 14.3) suffering from major depression were treated with amitriptyline (N = 31), citalopram (N = 29) and fluoxetine (N = 30). Direct medical costs and effectiveness (indicated by the number of hospitalization-free days) were assessed in a prospective, open, intent-to-treat study. RESULTS: Neither cost nor effectiveness were significantly different among the treatment groups. CONCLUSION: Amitriptyline treatment is not less expensive nor more effective than citalopram or fluoxetine therapies. There is no advantage in restricting patients from treatment with SSRIs, which have fewer adverse effects and a decreased risk of a lethal overdosage in comparison with tricyclic antidepressants.

• MeSH
• Amitriptyline economics   therapeutic use   MeSH
• Antidepressive Agents economics   therapeutic use   MeSH
• Citalopram economics   therapeutic use   MeSH
• Depressive Disorder drug therapy   economics   MeSH
• Adult MeSH
• Fluoxetine economics   therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Drug Costs MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH
• Names of Substances
• Amitriptyline MeSH
• Antidepressive Agents MeSH
• Citalopram MeSH
• Fluoxetine MeSH

Some antidepressant drugs, especially tricyclic ones--(TCA), have cardiovascular side effects. To compare the effects of antidepressant drugs, the electrocardiogram (ECG), vectorcardiogram (VCG), and body surface maps (BSM) were recorded in psychiatric patients without cardiovascular diseases treated by a) TCA amitriptyline or dosulepin (daily dose 50-200 mg, 22 patients), b) lithium (serum level 0.66 +/- 0.08 meq/l, 21 patients), c) selective serotonine reuptake inhibitor citalopram (daily doses 20-60 mg, 30 patients), and in 23 control patients. In the TCA-treated patients, the heart rate was increased, QT and RR intervals shortened (p < 0.01, antimuscarinic effect). This was not observed in lithium- and citalopram-treated patients. All antidepressants decreased the absolute maximum values of depolarization isointegral maps, lithium and TCA reduced the initial and citalopram the later phase of depolarization. Citalopram slightly diminished the amplitude of the R wave. The results confirm the antimuscarinic effects of TCA in therapeutic doses and specify the intraventricular effects of antidepressants.

• MeSH
• Amitriptyline adverse effects   MeSH
• Muscarinic Antagonists MeSH
• Antidepressive Agents, Tricyclic adverse effects   MeSH
• Antidepressive Agents adverse effects   MeSH
• Citalopram adverse effects   MeSH
• Adult MeSH
• Dothiepin adverse effects   MeSH
• Mental Disorders drug therapy   MeSH
• Electrophysiology MeSH
• Electrocardiography MeSH
• Cardiovascular Diseases chemically induced   physiopathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Lithium adverse effects   MeSH
• Selective Serotonin Reuptake Inhibitors adverse effects   MeSH
• Heart drug effects   physiopathology   MeSH
• Heart Rate drug effects   MeSH
• Tachycardia chemically induced   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Amitriptyline MeSH
• Muscarinic Antagonists MeSH
• Antidepressive Agents, Tricyclic MeSH
• Antidepressive Agents MeSH
• Citalopram MeSH
• Dothiepin MeSH
• Lithium MeSH
• Serotonin Uptake Inhibitors MeSH

Gel electrophoresis of DNA was used for estimation of DNA changes caused in C6 glioma cells by treatment with psychotropic drugs (imipramine, amitryptiline and fluoxetine). Some discrete bands containing a population of short DNA fragments appeared after 1 and 5 days of cultivation. Apoptotic DNA breaks were verified at single cell level using the TUNEL test in cells treated with fluoxetine.

• MeSH
• Amitriptyline pharmacology   MeSH
• Antidepressive Agents pharmacology   MeSH
• Apoptosis * MeSH
• Fluoxetine pharmacology   MeSH
• DNA Fragmentation drug effects   MeSH
• Glioma pathology   MeSH
• Imipramine pharmacology   MeSH
• Humans MeSH
• Tumor Cells, Cultured MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Amitriptyline MeSH
• Antidepressive Agents MeSH
• Fluoxetine MeSH
• Imipramine MeSH

In the submitted case-history the authors publish the case of successful treatment of a 9-year-old girl whose life was at risk after intoxication with a large dose of amitriptyline. Concurrently they deal with the social background of emotional disorders and some peculiar features in this girl with suicidal behaviour; attention is also drawn to specific features of the psychopathological picture of psychiatric child morbidity.

• MeSH
• Amitriptyline poisoning   MeSH
• Child MeSH
• Humans MeSH
• Poisoning diagnosis   therapy   MeSH
• Suicide, Attempted MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Female MeSH
• Publication type
• English Abstract MeSH
• Journal Article MeSH
• Case Reports MeSH
• Names of Substances
• Amitriptyline MeSH

An isocratic reversed-phase high-performance liquid chromatographic method with on-line solid-phase extraction for the simultaneous determination of amitriptyline and nortriptyline in serum has been developed. A 250-microliters serum sample is injected directly onto a commercially available CN cartridge and, after a washing step, the retained solutes are backflushed onto a bonded-phase CN column using a column-switching technique and a mobile phase composed of acetonitrile (26%) and 0.05 M phosphate buffer with diethylamine. Serum is diluted with 0.1 M sodium lauryl sulphate and centrifuged before the injection. Detection at 210 nm ensures sufficient sensitivity. The recovery is almost quantitative and the relative standard deviation ranges from 2.8 to 8.0% for concentrations of 200-40 ng/ml. Being rapid and simple, the method is convenient for routine use.

• MeSH
• Amitriptyline blood   MeSH
• Humans MeSH
• Nortriptyline blood   MeSH
• Chromatography, High Pressure Liquid methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Amitriptyline MeSH
• Nortriptyline MeSH

In a 21-day investigation in 15 patients with depression the authors investigated the incidence of undesirable side-effects in relation to plasma amitriptyline levels. The authors found the upper range of plasma concentrations when the patient's risk is minimal as regards serious undesirable complications. This upper limit is 350 micrograms/l; as compared with previous work, they consider amitriptyline levels from 150 to 350 350 micrograms/l safe and therapeutically effective. The authors consider investigation of plasma levels indicated in risk patients and in patients with an inadequate response to treatment.

• MeSH
• Amitriptyline adverse effects   blood   therapeutic use   MeSH
• Depressive Disorder blood   drug therapy   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• English Abstract MeSH
• Journal Article MeSH
• Names of Substances
• Amitriptyline MeSH

The authors assessed in a 21-day investigation the levels of amitriptyline and its metabolites in plasma and saliva, using the RIA method, in an attempt to reveal the relationship between the therapeutic effect and the assessed concentrations. They did not find a clear relationship between the therapeutic effect and plasma levels; when eliminating extreme maximal and minimal values, we may speak of concentrations where clinical improvement is recorded: from 150 to 450 micrograms/l. The concentration in saliva correlated at higher levels with the plasma concentration; this gives a theoretical chance of screening by this method. From the clinical aspect it is essential to express an opinion on the development of side-effects in relation to plasma levels. This problem will be discussed in a subsequent paper.

• MeSH
• Amitriptyline analogs & derivatives   pharmacokinetics   therapeutic use   MeSH
• Depressive Disorder drug therapy   metabolism   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• English Abstract MeSH
• Journal Article MeSH
• Names of Substances
• Amitriptyline MeSH

In an attempt to establish a radioimmunoassay (RIA), imipramine and amitriptyline immunogens were prepared; desmethyl derivatives were converted into hemisuccinates, conjugated with bovine serum albumin and used for rabbit immunization. [3H]Amitriptyline (4.3 TBq/mmol) and [3H]imipramine (2.9 TBq/mmol) were prepared by catalytic dehalogenation or reductive alkylation. Dibenzazepines and dibenzcycloheptanodienes were determined in biological fluids by a direct method without deproteinization (lower detection limit of 0.5 microgram.l-1); using high-yield methods they were extracted from cell membranes. Assay of tricyclic antidepressants in humans showed that these substances disappear from plasma much earlier than from cell membranes. Dissociation of the antidepressants bound to cell membranes is slow and their plasma concentrations are not influenced by standing for 2 h at 4 degrees C. During preparing the membranes for binding studies these substances are not removed, and they may affect the results of the binding studies.

• MeSH
• Amitriptyline blood   MeSH
• Erythrocyte Membrane chemistry   MeSH
• Imipramine blood   MeSH
• Humans MeSH
• Ligands MeSH
• Radioimmunoassay methods   MeSH
• Reproducibility of Results MeSH
• Sensitivity and Specificity MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Amitriptyline MeSH
• Imipramine MeSH
• Ligands MeSH