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At least 847 records · Page 47Linked to original sources
PubMed1984

Platelet met-enkephalin immunoreactivity and 5-hydroxytryptamine concentrations in migraine patients: effects of 5-hydroxytryptophan, amitriptyline and chlorimipramine treatment.

In thirty patients with common migraine the platelet concentrations of met-enkephalin immunoreactivity (ME) (76 +/- 9 pg/mg protein) were similar to those in 23 healthy volunteers (77 +/- 5), suggesting that there is no alteration in the ME pool in this biochemical compartment in migraine. Chronic treatment (4 weeks) with drugs that interfere with 5-hydroxytryptamine (5-HT) synthesis or uptake induced the expected changes in platelet 5-HT levels, i.e. a rise following administration of the 5-HT precursor 5-hydroxytryptophan (daily dose: 300-500 mg, n = 9) and a decrease after amine uptake inhibition by amitryptyline (30-75 mg, n = 7) and even more by chlorimipramine (30-50 mg, n = 9). Platelet ME concentrations rose by up to approximately 90% over the basal values after either 5-hydroxytryptophan (significantly from week 2) or amitriptyline (at week 2) and were unchanged after chlorimipramine, indicating that 5-HT and ME concentrations in platelets can vary independently. The high platelet ME levels following 5-hydroxytryptophan and amitriptyline cannot be explained at present. They might be due either to increased ME synthesis, possibly in the megakaryocyte, or to decreased utilization by platelets or both.

5-Hydroxytryptophan↗
PubMed2002

Effect of amitriptyline on gastric ulceration.

Amitriptyline significantly inhibited alcohol, aspirin, indomethacin and cold-restraint stress-induced ulceration. Secretory studies conducted in pyloric-ligated rats revealed that the drug, at the doses employed, significantly reduced total acidity and protein content. However, significant reductions of the gastric volume were only observed at the highest dose of the drug. In another set of experiments, when 50% alcohol (v/v) was administered to the pyloric-ligated rats pretreated with amitriptyline, it was observed that the drug significantly reduced the pH, total acidity and protein content.

Amitriptyline↗
PubMed1977

Three double-blind comparative trials of mianserine (ORG GB 94) and amitriptyline in the treatment of depressive illness.

The results of double-blind comparative trials carried out simultaneously in three Finnish hospitals are presented. The antidepressant activity and side-effects of mianserine (ORG GB 94) and amitriptyline were compared. No statistically significant differences were found between the two treatments. It was found, however, that mianserine had clearly less anticholinergic side-effects than amitriptyline.

Adolescent↗
PubMed1999

Effects of amitriptyline, amitriptylinoxide, doxepine and clozapine on N-methyl-D-aspartate-evoked release of [3H]-acetylcholine in rat caudatoputamen.

The tricyclic antidepressants amitriptyline (CAS 549-18-8), amitriptylinoxide (CAS 4317-14-0) and doxepine (CAS 1229-29-4) as well as the atypical neuroleptic clozapine (CAS 5786-21-0)--all of them substances with well-established clinical efficacy--were investigated in order to elucidate their effect on N-methyl-D-aspartate (NMDA) receptor-mediated events. Modulation of NMDA receptor function was studied using the model of NMDA-evoked [3H]-acetylcholine ([3H]-ACh) release in slices of rat caudatoputamen. All substances reduced [3H]-ACh release in a concentration dependent manner. Significant inhibition occurred in the low micromolar range with the exception of amitriptylinoxide which was less potent in vitro (amitriptylinoxide is not being metabolized in vitro). Amitriptyline and clozapine at 10 mumol/l both decreased the maximum effect of NMDA by around 17%, but left its EC50 unchanged. This suggests a "classical" non-competitive antagonism and excludes an uncompetitive or "use-dependent" antagonism. Considering the important role of NMDA receptor-mediated effects in spinal nociception the analgesic properties of tricyclic antidepressants may partly be explained by their inhibitory action on spinal NMDA receptors, in addition to their enhancement of monoaminergic transmissions in the dorsal horn.

Acetylcholine↗
PubMed1994

Heart rate variability in depressed patients and differential effects of paroxetine and amitriptyline on cardiovascular autonomic functions.

Twenty-four unmedicated patients with episodes of major depression (DSM-III-R) and an age- and sex-matched group of 24 normal subjects underwent a heart rate analysis. The battery of cardiovascular reflex tests included the coefficient of variation while resting (CVr) and during deep breathing (CVdr), a spectral analysis of heart rate variability, the Valsalva test, and the posture index. The depressed patients showed no significant abnormalities in any of the tests as compared to the healthy subjects. The 24 patients were randomly allocated for treatment with either amitriptyline or paroxetine. During treatment with 20 mg paroxetine per day, patients showed no changes in cardiovascular autonomic function tests after 14 days. However, treatment with 150 mg amitriptyline per day decreased all heart rate parameters significantly due to anticholinergic side effects, except heart rate, which increased significantly. As autonomic side effects are a potential hazard of antidepressant therapy, the data suggest that paroxetine is an appropriate antidepressant for cases with pre-existing cardiovascular autonomic neuropathy.

Adult↗
PubMed1986

A double-blind comparative trial of zimelidine, amitriptyline, and placebo in patients with mixed anxiety and depression.

We performed a randomized, double-blind clinical trial comparing the efficacy and safety of zimelidine with amitriptyline and placebo in outpatients with major depression, in particular patients with mixed anxiety/depressive symptomatology. Overall, amitriptyline was more effective than zimelidine and placebo after 4 weeks of treatment. However, when those patients with more severe depression were specifically examined, both antidepressants were equal in efficacy and superior to placebo. We also found no evidence for a greater likelihood of a zimelidine-induced peripheral neuropathy in this study. The present results suggest that zimelidine may be more effective in the treatment of severely depressed patients, rather than those with more mild mixed anxiety/depressive syndromes.

Adult↗
PubMed1983

Pharmacokinetics of amitriptyline N-oxide in rats after single and prolonged oral administration.

Amitriptyline N-oxide (AMINO) was given to male Wistar rats orally in single and multiple doses, and the levels of the drug and its main metabolite amitriptyline (AMI) were assayed in blood and brain by HPLC. After the single dose of AMINO (20 mg/kg), the levels of the parent compound and of AMI in the brain were higher than in blood. In the brain Cmax of AMINO and AMI were similar, whereas in the blood Cmax of AMI was considerably lower than that of the parent compound. After chronic treatment with AMINO (10 mg/kg twice daily, at 12 h intervals, for 14 days) the brain level of AMI reached the value of approx. 4 micrograms/g of tissue and remained nearly stable for 12 h after the last dose. Brain Cmax of AMINO was approx. 2 micrograms/g; the drug was eliminated more rapidly than AMI and 24 h after the last dose it was not detectable. The blood level of AMINO exceeded the level of AMI, but the difference was less marked than that observed after a single dose. The brain and blood levels of both drugs were considerably higher than those observed in the acute experiment. When AMI was given to rats chronically (dosage and schedule as above) its blood and brain levels were 2-5 times higher than the corresponding levels of AMI after treatment with AMINO, and its elimination was more rapid. Our results indicate that after oral administration of AMINO to rats AMI is formed in significant amounts, its brain level is high and becomes more stable after chronic treatment.

Administration, Oral↗
PubMed1982

A double-blind clinical trial of nomifensine vs. amitriptyline in depressed patients.

This article describes a controlled clinical trial comparing nomifensine and amitriptyline in endogenously depressed inpatients. It is also the first trial of the ICPP-BLIPS, a computer based clinical trial data documentation system. Using strict methodological criteria, careful quality control and comprehensive and systematic data display and data analysis, we have been able to show clearcut efficacy differences between nomifensine and amitriptyline (favouring the later) and clearcut differences in the profile of side effects between these drugs. Future studies utilizing this methodology are recommended were definitive and documented results of clinical trials are desired.

Adult↗
PubMed1982

[Comparison of the Hamilton Depression Rating Scale and the Self Rating Scale BS (v. Zerssen) within a double blind study on the antidepressant effects of trazodone verus amitriptyline (author's transl)].

From October 1977 until March 1978 a prospective study was performed on 30 depressive patients of both sexes, age 20 to 60 years. In a double-blind design patients received either amitriptyline or trazodone for 28 days. The course of therapy was controlled six times by means of the Hamilton Rating Scale for Depression (HRS) and the Zerssen-Contentment Scale (BS). The following results were obtained: By the statistical analysis of the HRs scores no difference in the antidepressant properties of trazodone and amitriptyline can be demonstrated. The same result is obtained by use of the BS scores. Therefore the antidepressant efficacy of the two medications can be called equal. When comparing day 10 to day 0, a correlation between the two data pools of RSp = 0.719 (p less than 0.01) according to Spearmen was found. Upon comparing the 28th day with the pre-treatment day, RSp comes out to be 0.809. When applying Anova no significant correlation for the pre-treatment day can be demonstrated (RL = 0.260); yet at the end of the study the correlation comes out to be extremely high (RL = 0.940, p less than 0.1). When considering each day of the study, RL results to be 0.808 (p less than 0.001). Thus, a high correlation can be demonstrated for the HRS and BS.

Administration, Oral↗
PubMed1982

A controlled double-blind study of femoxetine and amitriptyline in patients with endogenous depression.

The new selective serotonin (5-HT)-uptake inhibitor femoxetine was compared with amitriptyline in a double-blind clinical trial comprising 77 depressed patients. The depressive symptoms were evaluated with the Hamilton rating scale, and a global clinical evaluation. Both drugs showed an antidepressive effect and no significant differences were found. Femoxetine induced a significantly lower frequency of dry mouth and blurred vision; this difference is presumably due to the weak anticholinergic effect of this substance. A small but significant weight loss was observed in the femoxetine group but not in the amitriptyline group.

Amitriptyline↗
PubMed1982

Central action of amitriptyline N-oxide.

The central action of amitriptyline N-oxide (AMINO) has been compared with amitriptyline (AMI) in biochemical and pharmacological studies in rats and mice. It has been found in rats that both drugs prevent 6-OH-dopamine-induced depletion of brain noradrenaline (NA). At the same time AMINO increases and AMI lowers the NA level, both being without effect on 3-methoxy-4-hydroxyphenylglycol concentrations in the brain. AMINO and AMI potentiate the depletion of 5-hydroxytryptamine (5-HT) induced by p-chloroamphetamine in the rat brain and it may be considered as evidence that both drugs do not inhibit 5-HT uptake in vivo. Neither AMINO nor AMI affects the rat brain level of 5-HT but at higher doses they elevate the 5-hydroxy-indoleacetic acid concentrations. AMINO antagonizes the head twitch reaction induced by 5-hydroxytryptophan in mice and tryptamine convulsions in rats. The hyperthermia induced by fenfluramine (in rats at a high ambient temperature) as well as the stimulation of the hind limb flexor reflex in spinal rats, induced by fenfluramine or LSD, are also inhibited. AMINO antagonizes the 5-HT-induced increase in blood pressure in pithed rats. All the above effects are similar to those induced by AMI, only the active doses of AMINO are higher. The results presented indicate that AMINO, like AMI, inhibits NA uptake and is a 5-HT antagonist.

5-Hydroxytryptophan↗
PubMed1979

Seizures during lithium-amitriptyline therapy.

Epileptiform seizures occurred in a 34-year-old woman who was receiving amitriptyline and lithium carbonate therapy for treatment of endogenous depression. While receiving amitriptyline maintenance therapy, she was given lithium on two separate occasions, and despite serum levels of lithium in the therapeutic range, grand mal seizures developed. The seizures may represent a toxic reaction either to lithium or to combined drug therapy. Controlled studies are needed to evaluate both the efficacy and toxicity of combined drug therapy in affective disorders.

Adult↗
PubMed2006

Prolonged clinical effects in modified-release amitriptyline poisoning.

BACKGROUND: Tricyclic antidepressant poisoning is often associated with significant cardiovascular and central nervous system toxicity. Effective treatment includes the use of appropriate gastric decontamination techniques, the administration of sodium bicarbonate, and meticulous supportive care. Tricylcic antidepressant toxicity typically lasts 24-48 hours following a significant overdose. CASE REPORT: We describe a case of tricyclic antidepressant poisoning where significant clinical toxicity (QRS prolongation, metabolic acidosis) was observed for up to 4 days following ingestion of a modified-release preparation of amitriptyline. Successful patient recovery was associated with the use of multidose activated charcoal and repeated administration of intravenous sodium bicarbonate. CONCLUSIONS: Clinicians should be aware of the potential for prolonged tricyclic toxicity in patients who have ingested modified-release amitriptyline in overdose. Gastric decontamination techniques such as multidose activated charcoal and whole bowel irrigation should be considered where there is evidence of ongoing tricyclic antidepressant absorption or clinical toxicity following ingestion of a modified-release preparation. These interventions may be indicated for prolonged periods (greater than 36 hours) post ingestion.

Acidosis↗
PubMed1999

Extrapolating in vitro data on drug metabolism to in vivo pharmacokinetics: evaluation of the pharmacokinetic interaction between amitriptyline and fluoxetine.

Recently, models have been proposed to extrapolate in vitro data on the influence of inhibitors on drug metabolism to in vivo decrement in drug clearance. Many factors influence drug clearance such as age, gender, habits, diet, environment, liver disease, heredity, and other drugs. In vitro investigation of hepatic cytochrome P450 activity has generally centered on genetic influences and interactions with other drugs. This group of enzymes is involved in many, although not all, drug interactions. The interaction of amitriptyline and fluoxetine is an example. Of the different in vitro paradigms, interaction studies utilizing human liver microsomal preparations have proved to be the most generally applicable for in vitro scaling models. Assuming Michaelis-Menten conditions and applying nonlinear regression, a hybrid inhibition constant (Ki) can be generated that allows classification of the inhibitory potency of an inhibitor toward a specific reaction. This constant is largely independent of the substrate concentration, but in vivo relevance is critically dependent on the inhibitor concentration in the site of metabolic activity, the liver cell cytosol. Many lipophilic drugs are extensively bound to plasma protein but, nonetheless, demonstrate extensive partitioning into liver tissue. This is not compatible with diffusion only of the unbound drug fraction into liver cells. The introduction of a partition factor, based on data from a number of possible sources, provided a reasonable basis for the scaling of in vitro data to in vivo conditions. Many interactions could be reconstructed or predicted with greater accuracy and clinical relevance for interactions such as terfenadine or midazolam and ketoconazole. Even for less marked interactions such as amitriptyline and fluoxetine, this model provides a forecast consistent with the clinically observed range of 22-45% reduction in oral clearance, although this interaction is complicated by the presence of two inhibitors, fluoxetine and norfluoxetine. The concept of in vitro-in vivo scaling is promising and might ultimately yield a fast and more cost-effective screening for drug interactions with reduced human drug exposure and risk.

Amitriptyline↗
PubMed1998

A randomized, double-blind, placebo-controlled study of moclobemide and amitriptyline in the treatment of fibromyalgia in females without psychiatric disorder.

OBJECTIVE: To study the usefulness of moclobemide and amitriptyline in the treatment of fibromyalgia (FM) in females without psychiatric disorder. METHODS: In the present four centre, 12 week study, 130 female FM patients not suffering from psychiatric disorders were randomized to receive amitriptyline (AMI; 25 37.5 mg), moclobemide (MOCLO; 450-600 mg) or identical placebo. RESULTS: Seventy-four, 54 and 49 per cent of patients on AMI, MOCLO and placebo, respectively, were judged as responders. The patients on AMI also managed best regarding the respective improvements during the trial in general health, pain, sleep quality and quantity, and fatigue on visual analogue scales (VAS), the areas of the Nottingham Health Profile (NHP), as well as in the three Sheehan's functional disability scales. In the within-group comparisons, MOCLO also improved pain assessed both on VAS and on the NHP pain dimension, but the improvement was invalidated by the poor success of the drug with regard to sleep. The tolerabilities of all three drugs were comparable. CONCLUSION: The study indicates that MOCLO may not be helpful in FM patients free from clinically meaningful psychiatric problems.

Adolescent↗
PubMed1994

Postmortem changes in blood amitriptyline concentration.

Detailed toxicological studies were undertaken on two suicides by amitriptyline overdose, one with salicylate also. In the first case, 10 initial blood samples taken 21 h after body discovery and an estimated 28 1/2 h after overdose had drug concentration (mg/L) ranges of 2.5-12 for amitriptyline (AM), 0.7-3.1 for nortriptyline (NOR), and 81-244 for salicylate (SAL). Ten blood samples taken 42 h later showed corresponding ranges of 1-39 AM, 0.6-7.0 NOR, and 86-310 SAL. Sample haemoglobin concentrations (range, 8.7-23.5 g/dl) did not correlate with drug concentrations. Postmortem increase in pulmonary vein AM concentration occurred more rapidly than in the pulmonary artery, likely reflecting relative ease of diffusion across the vessel walls from lung (AM, 60 mg/kg). In nine tissue samples, drug concentrations (mg/kg) were highest in the liver: AM, 301; and SAL, 670. Considerable drug residue was present in gastric contents, duodenal contents, and seven sequential small bowel contents. In both cases, sanguineous putrefactive pleural fluid showed higher AM concentrations on the left than on the right (2.0 vs 1.4 and 23 vs 16), likely reflecting diffusion from gastric drug residue. The detailed case data illustrate the intensity and complexity of postmortem drug diffusion from reservoirs in solid organs, such as the lungs, and unabsorbed gastric residue, into the blood and putrefactive fluids.

Adult↗
PubMed1994

Comparative effects of fluoxetine, amitriptyline and serotonin on functional motor recovery after sensorimotor cortex injury.

A recent investigation of the effects of the antidepressants desipramine and trazodone on behavioral recovery in brain-injured animals suggested that antidepressants, which act to increase noradrenergic activity in the brain, may facilitate the rate of recovery, whereas those that act to increase serotonergic (5-HT) activity may hinder recovery and reinstate deficits in recovered animals. The present study was designed to evaluate these findings further by assessing the effect of a single intraperitoneal injection of fluoxetine (a relatively pure 5-HT reuptake blocker), amitriptyline (a mixed 5-HT and noradrenergic reuptake blocker with alpha 1-adrenergic receptor blocking activity) or a single intraventricular infusion of 5-HT on recovery of beam-walking ability in animals with a unilateral sensorimotor cortex injury. None of the drugs significantly affected the rate of recovery. Although fluoxetine was ineffective in reinstating the motor deficit in recovered animals, amitriptyline reinstated the deficit in a dose-dependent fashion. Infusion of 5-HT resulted in an extremely transient reinstatement of the deficit, which was largely attributable to its short-term sedative properties. These results suggest that 5-HT may be less involved in functional recovery than previously thought. They also add further support to previous findings that indicate that drugs which act to antagonize alpha 1-adrenergic activity (e.g., phenoxybenzamine) may interfere with motor recovery after sensorimotor cortex injury. An appreciation of the potential impact of certain antidepressants on functional recovery in brain-injured patients appears warranted.

Amitriptyline↗