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PubMed1986

Irregular chronic stress related selective presynaptic adaptation of dopaminergic system in rat striatum: effects of (-)deprenyl and amitriptyline.

Rats were exposed to irregular chronic stress (IRCS, an animal model of depression). Changes in dopamine and serotonin utilization by striata and hippocampi were measured. IRCS did not influence serotonin uptake, serotonin, dopamine, 5-hydroxyindolacetic acid and homovanillic acid levels, while it decreased 3,4-dihydroxyphenylacetic acid level and dopamine uptake. This would reflect selective presynaptic adaptation to IRCS. Neither (-)deprenyl (21 X 0.25 mg/kg, s.c.), nor amitriptyline (21 X X 15 mg/kg, i.p.) could prevent the effects of IRCS.

Adaptation, Physiological↗
PubMed1988

Effects of perphenazine, diazepam and nitrazepam on amitriptyline metabolism in rat.

Repeated coadministration of amitriptyline (AMT) and perphenazine (PPZ) decreased the AMT-induced increase of hepatic microsomal aminopyrine N-demethylase, aniline hydroxylase, NADPH-cytochrome c reductase and UDP-glucuronyltransferase (UDP-GT) activities in rats. This may be explained by a fact that inhibition of AMT metabolism in hepatic microsomes by PPZ led to increase the non-conjugated formation of AMT and its metabolites in the liver, brain, urine and feces. On the other hand, a slight decrease of drug metabolizing enzyme activity by diazepam (DZP) but not by nitrazepam (NTZ) was enhanced by combined treatment of AMT, whereas the enhancement of UDP-GT activity by DZP or NTZ was suppressed by coadministration of AMT. At the same time there was no clear increase of non-conjugated formation of AMT metabolites in rat urine and feces during combined treatment.

Amitriptyline↗
PubMed1988

Valpromide increases the plasma concentrations of amitriptyline and its metabolite nortriptyline in depressive patients.

The effects of valpromide on amitriptyline (AMT) and nortriptyline (NT) plasma levels were examined in 20 depressed inpatients. They all were treated with AMT, 125 mg once daily, and 10 patients also received 600 mg of valpromide daily after 10 days on AMT. In the 10 patients receiving valpromide in addition to AMT, the mean AMT level increased from 70.5 +/- 35 to 105.5 +/- 49 ng/ml (p less than 0.0003) and the mean NT level from 61.0 +/- 34 to 100.5 +/- 65 ng/ml (p less than 0.01). This increase was not related to valpromide metabolite plasma levels, nor to the age of the patients. The addition of valpromide to a stable AMT regimen may result in an increase of antidepressant plasma level with clinical implications.

Adult↗
PubMed1988

Determination of amitriptyline and cocaine by GC and GC/MS in biological fluids.

A method of identification and quantitative determination of amitriptyline and cocaine at trace levels in biological fluids is described. After the extraction of both drugs from the biological material in an alkaline medium, and posterior purification and concentration of the extract, one proceeds to unequivocal identification using the combined capillary GC/MS system with the Selected Ion Monitoring (SIM) technique. Quantitative determination is carried out by GC with a N-P detector. The precision of the method and limits of sensitivity are presented.

Amitriptyline↗
PubMedDate not supplied

Leu-enkephalin content in rat brain during prolonged treatment with imipramine or amitriptyline.

The influence of imipramine (IMI) or amitriptyline (AMI) on the level of immunoreactive leu-enkephalin (ir-LENK) in the striatum and hypothalamus was studied in rats. Each drug was given by drinking water once or over periods of 1, 3, 4 and 6 months. The ir-LENK in brain perfusates was measured after 3 or 9 month treatment with IMI. The results obtained indicate that during prolonged administration of IMI the central enkephalinergic system is dynamically changed. We have observed that chronic (but not acute) administration of IMI induced different effects on LENK level in the examined structures than changes caused by treatment with AMI.

Amitriptyline↗
PubMed1988

Phenytoin prophylaxis of cardiotoxicity in experimental amitriptyline poisoning.

Tricyclic antidepressants (TCA) are drugs with Type IA antiarrhythmic properties that cause severe cardiac conduction blocks, hypotension, and ventricular dysrhythmias at toxic levels. Phenytoin has been proposed as a prophylaxis and treatment of these dysrhythmias, since it is thought to improve conduction in this setting. Anesthetized dogs were given a loading dose of phenytoin, followed by constant amitriptyline infusion until death. Variables known to affect TCA toxicity, such as arterial pH, were carefully controlled. There were no significant differences between the phenytoin and control group in any physiologic parameter, including toxicity, drug levels, or dose to death. However, duration and frequency of episodes of ventricular tachycardia were dramatically increased in the phenytoin group. It is concluded that prophylactic phenytoin in this animal model provides no benefits and may in fact increase the severity of ventricular tachycardia and hypotension. In addition, it is speculated that similar adverse effects of phenytoin might be seen in other Type IA antiarrhythmics if the extremely toxic levels seen in this study with TCA were reached.

Amitriptyline↗
PubMed1977

A comparison of maprotiline (Ludiomil) and amitriptyline (1).

The study described here was designed to see if it was possible to show an earlier onset of action for maprotiline (Ludiomil) compared with amitriptyline while at the same time demonstrating equal long-term effectiveness and certainly no greater side-effects. A between-patient double-blind trial with 40 patients supported these aims and was statistically significant (p less than 0.001) with regard to early onset of antidepressant effect.

Amitriptyline↗
PubMed1986

Quantitative homogeneous enzyme immunoassays for amitriptyline, nortriptyline, imipramine, and desipramine.

We describe specific EMIT homogeneous enzyme immunoassays for amitriptyline, nortriptyline, imipramine, and desipramine in patients' serum samples. Before analysis, an easily performed extraction step involving the use of 500 microL of sample and a 1-mL disposable column eliminates cross-reacting polar metabolites. The range of the standard curve for the first three drugs is 25 to 250 micrograms/L, and for desipramine is 50 to 500 micrograms/L. Within-run and between-run CVs are less than 10% throughout the range of the assays. Results for patients' samples obtained by this method and by "high-performance" liquid chromatography compare well, showing a slope range of 0.94-1.04 and correlation coefficients ranging from 0.93 to 0.96, depending on the assay.

Amitriptyline↗
PubMed1985

A double-blind comparison of clovoxamine and amitriptyline in the treatment of depressed outpatients.

Forty-two outpatients with major depression were treated in a 4-week double-blind parallel-group comparison of the new antidepressant clovoxamine--a member of oximethers of aralkylketones--with amitriptyline. The two drugs were comparable in efficacy, although because of the small sample size a moderate clinical difference between treatments may not have been detected. The magnitude of unwanted effects also was comparable, but clovoxamine produced fewer "anticholinergic" effects; this was determined by patient complaints of typical anticholinergic symptoms, by decreased salivary flow, and by a new signal detection memory test.

Adolescent↗
PubMed1985

Long-term amitriptyline in chronic depression.

Medication was discontinued under a placebo-controlled, double-blind, six-month protocol with 17 chronically depressed patients who had been taking an average daily dose of 138 mg amitriptyline (AMI) for an average of 3.7 years. Only one of nine patients became depressed on active medication, while of the 15 patients receiving a placebo trial, 11 had a depressive recurrence at an average time of 9.3 weeks. These 11 were subsequently restarted on AMI, and responded similarly to the way in which acutely depressed patients respond, although the patients showed either a need for less AMI or decreased symptoms, compared to entry. Tolerance did not develop to anticholinergic side-effects during long-term medication. Twelve of the 15 patients on placebo showed a withdrawal reaction during the first few weeks of tapered AMI discontinuation which could be distinguished from recurrence of depression. This study suggests that the majority of patients on long-term antidepressant will suffer a recurrence of depressive symptoms when the medication is discontinued.

Amitriptyline↗
PubMed1985

A controlled trial of amitriptyline and cianopramine in major depression.

The therapeutic efficacy and adverse effects of amitriptyline and cianopramine were compared in a double-blind, randomized, flexible-dose trial in 40 patients with major depressive episodes. The two drugs were equally effective in reducing scores on the Hamilton Psychiatric Rating Scale for Depression and on a global scale. Both drugs were associated with significant adverse effects. Fewer adverse effects were associated with cianopramine, however, which lacks antimuscarinic activity.

Amitriptyline↗
PubMed1986

The DST as a predictor of acute response to treatment with ECT, chlorimipramine, amitriptyline, and phenelzine.

Plasma cortisol levels of 41 patients suffering from major depressive episodes were measured at 4 p.m. and 10 p.m. one day after administration of 1 mg dexamethasone at 10 p.m. Comparison of cortisol results to clinical improvement measured by the Beck Depression Inventory before and after 5 weeks of treatment with either ECT, chlorimipramine, amitriptyline, or phenelzine showed no difference between nonsuppressors and suppressors in relation to clinical improvement. Clinical prediction of the outcome of acute response to these treatments using an initial DST does not seem feasible.

Amitriptyline↗
PubMed1985

Plasma levels of amitriptyline: effect of age and sex.

Routine doses of amitriptyline were given to 110 inpatients who were examined for clinical predictors of variability in steady-state total tricyclic antidepressant plasma levels. Increasing age (p less than .01) and female sex (p less than .05) were associated with higher plasma levels.

Adult↗
PubMed1985

[The use of low-dose amitriptyline in psychogeriatrics. A clinical, pharmacokinetic and pharmacogenetic study].

Two groups of six depressive psychogeriatric patients (age 69-93) have been treated for three weeks with either 25 mg or 50 mg of amitriptyline (AT) per day. Before the beginning of the treatment and after 8, 15 and 22 days of medication, the patients (7 outpatients and 5 hospitalized patients) underwent various psychopathological tests (Hamilton, Crichton) and biochemical investigations, i.e. clinical chemistry and hematology, analyses of AT and nortriptyline (NT), in the plasma. In some subjects the hydroxylated metabolites and the binding of these substances to plasma proteins were also measured. Except one patient, all responded favourably to the treatment. No difference between the two doses has been observed as regards their clinical efficacy and incidence of side effects. The plasma levels of AT and NT were below those generally recommended in the literature. The monitoring served to identify some cases of noncompliance and, in one patient, a deficiency of hydroxylation of AT, confirmed by the debrisoquine test. These results suggest that the "therapeutic window" needs redefinition and that low-dose medication with antidepressants is indicated in a psychogeriatric population.

Aged↗
PubMed1974

Treatment of the painful shoulder syndrome with amitriptyline and lithium carbonate.

Thirty-four patients with painful shoulder syndrome (PSS) were psychologically assessed and the results compared with those from a control group presenting other musculoskeletal disorders. A significantly greater prevalence of depression was found in the former group. Fifty-six patients with PSS were treated with only lithium and amitriptyline for four months; 44 patients showed marked clinical improvement and radiologic clearing of dystrophic calcification. Lithiumamitriptyline therapy, when compared with physiotherapy in another series of 11 patients, was found to be far superior. Some possible biochemical links between depression and PSS are outlined, and the theory that PSS may be a clinical entity of psychogenic origin is discussed.

Adult↗
PubMed1979

The effects of physostigmine on amitriptyline induced cardiotoxicity in dogs.

When 0.5 mgs of physostigmine salicylate was injected intravenously into adult beagle dogs which had been severely poisoned with amitriptyline, a transient improvement in cardiac output, systolic blood pressure, intraventricular conduction and in the maximum rate of rise of arterial blood pressure (arterial dP/dT max.) was observed. These effects were maximal at 15-20 minutes after injection and had largely disappeared 30 to 35 minutes after the injection.

Amitriptyline↗
PubMed1978

Relative toxicity of amitriptyline, imipramine, maprotiline and mianserin after intravenous infusion in conscious rabbits.

1. Amitriptyline, imipramine, maprotiline and mianserin were administered intravenously to conscious rabbits. 2. Of the four compounds, mianserin was the least toxic, as assessed by the occurrence of convulsions, cardiotoxicity and eventual death. 3. The applicability of the results from this test system to man is debatable, but the indications are that the relative toxicity of mianserin may be low.

Amitriptyline↗
PubMed1983

A comparative study of bupropion and amitriptyline in depressed outpatients.

A double-blind controlled trial comparing a standard antidepressant drug, amitriptyline, with a new compound, bupropion, was conducted at six centers. There was a placebo washout, after which patients were assigned in a randomized fashion to one of the two treatments. No significant difference was found in therapeutic response to the two drugs after 4 weeks of treatment. Anticholinergic and cardiovascular side effects were less common in the bupropion-treated patients.

Adolescent↗