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At least 1,279 records · Page 71Linked to original sources
PubMed1983

Rapid high pressure liquid chromatographic determination of amitriptyline hydrochloride in tablets and injectables: collaborative study.

A previously reported high pressure liquid chromatographic method for the determination of amitriptyline hydrochloride in dosage forms was modified to permit its use as a stability-indicating method. The modified method, entailing a nitrile bonded microparticulate column, a methanol-0.005M ammonium acetate (90 + 10) mobile phase, and photometric detection at 239 nm, was collaboratively tested by 10 laboratories. Each collaborator received samples of synthetic and commercial tablets and injections. The recovery from a synthetic injection at the 10.06 mg/mL spiking level averaged 98.6%. The amount of declared found in commercial injections averaged 103.1%. The pooled reproducibility SD (CV%) and repeatability SD (CV%) were +/- 2.12 (2.15) and +/- 1.81 (1.84), respectively. The recovery from synthetic tablet composite at the 7.45% spiking level averaged 102.0%. The amount of declared found for commercial 25 mg and 100 mg tablets averaged 96.7 and 97.9%, respectively. The pooled reproducibility SD (CV%) and repeatability SD (CV%) for these 3 tablet samples were +/- 1.89 (1.86) and +/- 1.66 (1.64), respectively. Content uniformity analysis of commercial 25 mg and 100 mg tablets (n = 10) gave amounts of declared values averaging 100.5% (range 92.4-108.8%) and 99.3% (range 89.6-107.0%), respectively. The pooled reproducibility SD (CV%) and repeatability SD (CV%) were +/- 3.23 (3.2) and +/- 2.78 (2.8), respectively. A commercial injectable preparation spiked with dibenzosuberone was also collaboratively analyzed by a thin layer method. The method was adopted interim official first action.

Amitriptyline↗
PubMed1983

Ventricular arrhythmias induced by doxepin and amitriptyline: case report.

A case is described of ventricular arrhythmias associated with doxepin and amitriptyline treatment in a patient with preexisting heart disease. A significant correlation was found between the occurrence of premature ventricular depolarizations and serum levels of both antidepressants.

Amitriptyline↗
PubMed1982

Amoxapine and amitriptyline: serum levels and clinical response in patients with primary unipolar depression.

Amoxapine, a new antidepressant of the dibenzoxazepine class, was compared with amitriptyline in 80 patients with primary unipolar depressive disorders. In a four-week double-blind trial, the two medications were equally effective and had similar onsets of therapeutic action. The range of side effects was similar, although there was a trend for fewer side effects in the amoxapine group. Serum levels were not related to therapeutic response for either medication.

Adolescent↗
PubMedDate not supplied

[Different effects of tricyclic (clomipramine and amitriptyline) and tetracyclic (maprotiline) antidepressors on the release of thyroid stimulating hormone, prolactin and growth hormone to thyrostimulating releasing hormone in patients with psychoaffective disorders (author's transl)].

The hormonal alterations induced by tricyclic and tetracyclic antidepressors (AD) were studied in patients with psychoaffective disorders (PAD) to ascertain the role of certain biogenic amines in the regulation of thyroid stimulating hormone (TSH), prolactin (PRL) and growth hormone (GH). The responsiveness of plasma TSH, PRL and GH to synthetic thyrostimulating release hormone (TRH; 250 microgram i.v.) was determined in 57 patients distributed in 5 groups according to the treatment: 10 non treated patients, 16 tricyclic (clomipramine and amitriptyline) treated patients, 6 patients treated by clomipramine in association with lithium, 6 tetracyclic (maprotiline) treated patients and 19 patients treated by major neuroleptics. Results of untreated patients were compared to those observed in 10 age and sex matched normal subjects. Basal plasma levels of TSH were normal in all the patients. The TSH response to TRH (delta TSH) was blunted in non treated patients. delta TSH was normal in the patients treated by maprotiline or neuroleptics and increased in the group treated by tricyclic AD in association with lithium. Basal plasma levels of PRL and PRL response to TRH (delta PRL) were decreased in the women treated by tricyclic AD, but remained normal under maprotiline. They were markedly increased in the neuroleptic group. No inadequate response of GH to TRH was noted in our series of patients. The different hormonal effects induced by AD--dissociation between delta TSH and delta PRL under tricyclics and normal or increased delta TSH under maprotiline--may be logically explained by the various ways of action of these AD on the brain monoamines. delta TSH decrease and tendency to an increased delta PRL observed with clomipramine argue for a serotoninergic regulation of these two hormones, whereas the normalisation of delta TSH under maprotiline argues for a noradrenergic regulation of this hormone. Effectively, tricyclic AD inhibits mainly the serotonin recaptation and tetracyclic inhibits rather norepinephrine recaptation. The persistent delta TSH increase observed in the group treated by the association clomipramine-lithium demonstrates that the tricyclics do not interact with the hypophyso-thyroid positive feedback.

Adult↗
PubMed1982

Role of the central adrenergic system in mediating amitriptyline-induced alteration in the mammalian blood-brain barrier in vivo.

All tricyclic antidepressants increase the degree of equilibration of [3H]water across the cerebral capillary (Ew) as measured by a dual-label radioactive tracer technique. By using amitriptyline (AMI) as a prototype, a series of studies was conducted to determine the mechanism for this drug effect. The AMI-induced increase in Ew was blocked by 6-hydroxydopamine ablation of central aminergic neurons and by pretreatment with phenoxybenzamine, an alpha adrenergic antagonist. Pretreatment with propranolol, a beta adrenergic antagonist, did not block the AMI-induced increase. Central serotonergic ablation by p-chloroamphetamine had no effect on the AMI-induced increase. Treatment with atropine and hydroxyzine separately also did not alter Ew. Based on these results, the AMI-induced increase in Ew appears to be mediated by the effect of the drug on central adrenergic neurons. The serotonergic, anticholinergic and antihistaminergic actions of AMI, by themselves, do not appear to play a role in this phenomenon. The results are compatible with the concept that the central adrenergic system functions, in part, to regulate the cerebromicrocirculation.

Amitriptyline↗
PubMed1983

Diabetic neuropathic pain: control by amitriptyline and fluphenazine in renal insufficiency.

Seven patients with diabetes of ten to 24 years' duration and renal insufficiency were treated with fluphenazine and amitriptyline in an attempt to control severe pain in the extremities. Six patients had relief of pain within five days of initiation of therapy. One patient had no pain relief despite mood alteration. The relief of pain persisted whether renal function was stable or declining. This form of therapy is safe and as effective in patients with neuropathic pain and mild to moderate renal insufficiency as in patients with normal renal function.

Adult↗
PubMed1981

Amoxapine and amitriptyline in the outpatient treatment of endogenous depression.

This double-blind investigation compared onset of action, efficacy, and safety of amoxapine and amitriptyline in 46 endogenously depressed outpatients. Statistical analysis demonstrated relatively few significant differences in improvement between the two groups. Most of the differences favored amoxapine, however, and on all measures there were clear trends favoring amoxapine for more rapid onset of action or greater overall efficacy or both.

Adolescent↗
PubMed1980

[Amitriptyline and imipramine poisoning].

Two cases of severe poisoning by tricyclic antidepressants (Amitriptylin, Imipramin) are reported. Both patients 3 and 11 years old children, developed a typical clinical picture with cardiovascular, neurological and atropine features. Beside a general supportive management, in one case physostigmin was used as antidote. Alternative treatments of enuresis in childhood are recommended.

Amitriptyline↗
PubMed1980

Amitriptyline therapy of obsessive-compulsive neurosis.

Substantial improvement in 2 patients with obsessive-compulsive neurosis resulted from the administration of amitriptyline. No other pharmacologic or psychologic intervention had previously been effective in these patients. This tricyclic antidepressant has a pharmacologic spectrum of action very similar to chlorimipramine. Both drugs cause significant impairment in serotonin (5-hydroxytryptamine) reuptake. Evidence for a relative deficit in the central availability of 5-hydroxytryptamine (5-HT) in obsessive-compulsive phenomena is presented and a rationale for the use of these agents evolves.

Adult↗
PubMed1995

N-demethylation of amitriptyline in vitro: role of cytochrome P-450 3A (CYP3A) isoforms and effect of metabolic inhibitors.

Biotransformation of amitriptyline (AMI) to its demethylated product nortriptyline (NT) was studied in vitro with human liver microsomes from four different donors, preselected to reflect a range of metabolic rates. Reaction velocity versus substrate concentration was consistent with a sigmoid Vmax model. Vmax varied from 0.42 to 3.42 nmol/mg/min, Km from 33 to 89 microM AMI. Ketoconazole was a highly potent inhibitor of N-demethylation, with a mean Ki value of 0.11 +/- 0.013 microM (+/- S.D.), whereas quinidine (up to 50 microM), a CYP2D6 inhibitor, and alpha-naphthoflavone (up to 5 microM), a CYP1A2 inhibitor only at low concentrations, showed no effect. All selective serotonin reuptake inhibitors (SSRIs) tested had an inhibitory effect on the formation of NT, with mean Ki values of 4.37 (+/- 3.38) microM for sertraline, 5.46 (+/- 1.95) microM for desmethylsertraline, 9.22 (+/- 3.69) microM for fluvoxamine, 12.26 (+/- 5.67) microM for norfluoxetine, 15.76 (+/- 5.05) microM for paroxetine, and 43.55 (+/- 18.28) microM for fluoxetine. A polyclonal rabbit antibody against rat liver CYP3A1, in antibody/microsomal protein ratios varying from 1:1 to 10:1, inhibited N-demethylation of AMI to an asymptotic maximum of 60%. These results are consistent with several case reports describing impairment of AMI metabolism by SSRIs. Inhibition of AMI demethylation by low concentrations of ketoconazole and by anti-3A antibody supports an important role for CYP3A isoforms in mediating this reaction.

1-Naphthylamine↗
PubMedDate not supplied

[Optimization of the components of intensive care of heart and hemodynamic disorders in patients with acute amitriptyline poisoning].

Cardio- and hemodynamics were examined in 56 patients with acute suicidal poisonings with amitriptyline, a tricyclic antidepressant, in order to select and optimize the main agents for intensive care of disorders developing in the circulatory system. Adsorption detoxication in parallel with adequate correction of volemic disorders was found to be advisable. A possibility of hemodynamic stabilization in patients with normo- and tachycardia without sharp hypotonia by nonspecific antidotes proserine or obsidan was shown, and by inotropic support with dobutrex in patients with signs of exotoxic shock. The mechanisms underlying the efficacy of therapy are discussed.

Acute Disease↗
PubMedDate not supplied

[Amitriptyline facilitates the analgesic effect of adrenal medulla autograft in the lumbar subarachnoid space of the rat].

OBJECTIVES: To investigate the possible enhancement of analgesic effect induced by treatment with amitriptyline (AMI) after the autografting of suprarenal medulla into the subarachnoid lumbar space in the rat. MATERIAL AND METHODS: Four experimental groups were formed (control + saline solution [SS]; control + AMI; transplant + SS and transplant + AMI). AMI (10 mg/kg i.p.) or SS was administered for 28 days after surgery. The tail-flick test, with baseline values taken before surgery, was used to measure threshold pain on days 1, 4, 7, 14, 21 and 28. RESULTS: Suprarenal medullae transplantation afforded evident analgesic effect from day 1 to day 28. Analgesic effect was enhanced in transplanted rats treated with AMI from day 4 of treatment, with more evident effect on day 28. No analgesic effect per se was observed in the control group. CONCLUSIONS: Our results confirm that grafting per se has an analgesic effect and that it can be improved by systematic treatment with AMI. These results suggest new possibilities for using suprarenal medulla grafts for pain.

Adrenal Medulla↗
PubMed1976

[Double-blind comparative study on the effects of lofepramine and amitriptyline in depressive outpatients (author's transl)].

The anticholinergic side-effects of tricyclic antidepressants are unpleasant for the patients. Lofepramine, a new tricyclic antidepressant, has in animal studies been shown to have weak anticholinergic effects and a low acute toxicity. The aim of the present study was to see whether these pharmacological properties led to a lower rate of side-effects in depressed patients. In a double-blind trial 40 outpatients were treated with lofepramine or amitriptyline. Assessments were made with the Hamilton Scale, the Wakefield Self-Assessment Scale and a Side-effect Scale. 33 patients completed the trial. Both drugs proved effective. There were small differences in favour of lofepramine both in therapeutic efficacy and frequency of side-effects.

Amitriptyline↗
PubMedDate not supplied

Tissue distribution and metabolism of amitriptyline after repeated administration in rats.

Plasma concentration, tissue distribution, and metabolism of amitriptyline (AMI) in rats pretreated with AMI (20 mg/kg/day, ip dose, for 7 days; treated) were compared with control rats. Plasma concentrations of AMI after intravenous administration (2 and 10 mg/kg) to the treated rat were significantly higher than those to the control rat in both doses. The difference in the plasma concentration between both groups may be caused by a change of tissue distribution of AMI, because the blood cell-to-plasma concentration ratio and the tissue-to-blood concentration ratio values for various tissues in the treated rat were smaller than those in the control, respectively. The plasma unbound fraction of AMI in the treated rat was significantly smaller (p < 0.05). alpha 1-Acid glycoprotein concentration in plasma of the treated rat was approximately twice that in the control rat. These results suggest that the decrease of tissue distribution of AMI in the treated rat may be caused by the decrease in the plasma unbound fraction of AMI with the increase of alpha 1-acid glycoprotein in plasma. The area under the plasma concentration-time curve for AMI and its main metabolite, nortriptyline, in the treated rat after intraportal administration of AMI was 1/3 and 3-fold those in the control rats, respectively. On the other hand, the hepatic intrinsic clearance (CLH,Int) of the unbound drug in the treated rat was approximately twice that of the control, suggesting that the increase of the (CLH,Int) by repeated administration of AMI may result in the induction of oxidative metabolism.

Amitriptyline↗
PubMed1994

Amitriptyline in the treatment of interstitial cystitis.

Limited data and an accumulated body of anecdotal experience with the tricyclic class of antidepressants suggest that this group of drugs (especially amitriptyline) may be an effective treatment modality in nonulcerative interstitial cystitis. Both the ease of administration and the relatively rapid onset of relief make these types of drugs appropriate to consider for first-line therapy after bladder distention has failed.

Amitriptyline↗
PubMed1993

[Poisoning with a high dose of amitriptyline in a 9-year-old girl].

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.

Amitriptyline↗