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At least 811 records · Page 45Linked to original sources
PubMed1989

Chronic treatment with amitriptyline produces subsensitivity to the hypothermic effects of clonidine.

1. Supersensitivity or up-regulation of presynaptic alpha 2-adrenoceptors may be involved in the pathogenesis of depression. 2. The authors used a thermoregulation paradigm to test the hypothesis that chronic treatment with a tricyclic antidepressant amitriptyline (AMI) produces subsensitivity to the hypothermic effects of the alpha 2 agonist clonidine. 3. Treatment with amitriptyline produced blunting of the hypothermic response to clonidine. 4. Subsensitivity persisted for at least 21 days--that point after the discontinuation of the tricyclic at which the animals were last challenged with clonidine. 5. These findings are consistent with previous reports that tricyclic antidepressants produce subsensitivity of alpha 2 adrenoceptors.

Amitriptyline↗
PubMed1990

Repeated treatment with amitriptyline or electroconvulsive shock does not affect thyrotropin releasing hormone receptors in discrete rat brain structures.

We studied the effect of repeated treatment with amitriptyline (10 mg/kg, p.o., twice daily for 14 days) or electroconvulsive shock (ECS) (once daily for 10 days) on the thyrotropin-releasing hormone (TRH) content and TRH receptors in the cerebral cortex, nucleus accumbens, striatum and septum of the rat. Repeated amitriptyline did not significantly affect the density or affinity of TRH receptors in the examined structures, but caused a marked increase in the TRH content in the striatum and nucleus accumbens. Long-term treatment with ECS reduced the density and affinity of TRH receptors in the septum only, but it increased the TRH concentration in the cerebral cortex and striatum. These results, together with the literature data, indicate that there is no simple relationship between the brain content (and release) of TRH and the functional sensitivity of TRH receptors on one hand, and the density of these receptors on the other.

Amitriptyline↗
PubMed1982

A controlled study of amitriptyline in the treatment of chronic pain.

This paper reports a study in which a double-blind controlled cross-over study of amitriptyline vs. placebo was carried out in a group of patients referred to a multidisciplinary pain clinic for the management of chronic intractable pain for which no substantial organic cause could be demonstrated. Of 52 patients entering the 12-week trial, 20 withdrew before completion. No differences were found in terms of global improvement on either agent. Subjective reports indicated a greater reduction in pain at 2 and 4 weeks on amitriptyline, but no difference at 6 weeks. None of the baseline measures was predictive of response.

Amitriptyline↗
PubMed1985

Reduction of arthritis and pain behaviour following chronic administration of amitriptyline or imipramine in rats with adjuvant-induced arthritis.

Tricyclic antidepressants (TCAs) are used extensively to treat chronic pain in man without an adequate explanation for their activity. The purpose of the present study was to investigate this problem by testing the effect of chronic TCAs in an animal pain model: the arthritic rat. Sprague-Dawley rats with adjuvant-induced arthritis were injected daily for 4 weeks with amitriptyline (10 mg/kg) or imipramine (10 mg/kg) or saline, beginning 21 days after the induction of arthritis. Baseline evaluations were made prior to the injection series and at 4 weeks, 24 h after the last injection. Both TCAs significantly reduced 'scratching' and increased 'exploring' behaviour, without changing the response to graded foot pressure. In addition clinical signs of arthritis (ankle circumference, swelling, conjunctivitis, balanitis ...) were significantly reduced, while mobility was increased. This study shows that both amitriptyline and imipramine decrease pain behaviour and arthritis in this chronic pain model. Possible 'antiinflammatory' effects of TCAs and their eventual 'analgesic' effect will be discussed.

Amitriptyline↗
PubMed1994

Postmortem release of amitriptyline from the lungs; a mechanism of postmortem drug redistribution.

An experimental rat model was used to study postmortem redistribution of amitriptyline (AMI). Two hours after a subcutaneous injection with 20 mg of amitriptyline, the rats (n = 40) were anaesthetized and blood samples were drawn from the femoral vein and the heart. The rats were then sacrificed by CO2 and left at room temperature for either 0.1, 1, 2, 5, 24, 48, or 96 h. Postmortem blood samples from the heart and the inferior vena cava, and tissue samples from the lungs, heart, liver, right kidney, thigh muscle, the wall of the abdominal vena cava and brain were analyzed by high performance liquid chromatography. A significant increase was observed within 2 h postmortem in heart blood and later also in blood from the inferior vena cava. At 96 h postmortem the concentration increase was 4.4 +/- 0.5-fold (P < 0.01) and 3.0 +/- 1.1-fold (P < 0.05) as compared to the antemortem values observed in heart blood and blood from the inferior vena cava, respectively (mean +/- SEM). In the lungs there was a fall in the concentration of AMI from 148 +/- 16.7 mumol/kg at 0.1 h to 49.1 +/- 7.8 mumol/kg at 96 h postmortem (P < 0.01). In the vessel wall of the abdominal vena cava there was also a significant fall in drug concentration, while in heart muscle and liver an increase in drug concentration was observed. In animals where the lungs were removed agonally (n = 7), the drug concentration in heart blood had increased significantly less at 2 h postmortem.(ABSTRACT TRUNCATED AT 250 WORDS)

Amitriptyline↗
PubMed1991

Interaction of mianserin, amitriptyline and haloperidol with guinea pig cerebral histamine H2 receptors studied with [125I]iodoaminopotentidine.

Tricyclic antidepressants were previously shown to potently inhibit the histamine-induced activation of H2 receptors linked to adenylate cyclase in cerebral membranes, and this effect was postulated to represent the mechanism of their therapeutic activity. However, these drugs were found to be much less potent (up to more than hundred-fold) at H2 receptors mediating cyclic AMP responses in intact cells. We have presently assessed whether this large difference in potency of antidepressants, also observed with haloperidol, results from a modified pharmacological specificity of the H2 receptor according to the medium composition. We have studied the binding of [125I]iodoaminopotentidine (125I-APT) to striatal or hippocampal membranes under various experimental conditions. At equilibrium the Kd of 125I-APT, a highly selective ligand for H2 receptors, was six times higher in a supplemented Tris buffer used for adenylate cyclase assays in cell-free systems than in a Krebs-Ringer medium used in studies with intact cells. The medium composition also variously affected the Ki values of the four compounds studied amitriptyline, mianserin, haloperidol and tiotidine. Whereas the Ki value of amitriptyline was little affected, that of the other compounds was four to five times lower in the supplemented Tris buffer than in the Krebs-Ringer medium. With the exception of tiotidine, the Ki values of other compounds in the binding test performed in this medium, were intermediate between those derived from the antagonism of histamine-induced cyclic AMP responses in membranes and intact cells. These data indicate that the difference between the two test responses is diversely attributable to several factors according to the compounds, the main ones being medium composition and possibly cell disruption.

Amitriptyline↗
PubMed1995

Fluvoxamine and fluoxetine: interaction studies with amitriptyline, clomipramine and neuroleptics in phenotyped patients.

The in vivo pharmacokinetic interaction between two selective serotonin reuptake inhibitors (SSRI) (fluvoxamine, fluoxetine) and tricyclic antidepressants (TCAs) (amitriptyline, clomipramine) or neuroleptics (haloperidol, cyamemazine, levomepromazine, propericiazine) was assessed in 29 in-patients. They were phenotyped twice with dextromethorphan and mephenytoin: first in steady state conditions while under treatment with TCAs or neuroleptics; and also 10 days after an associated treatment with fluvoxamine (150 mg day(-1)) or fluoxetine (20 mg day(-1)). A clear and statistically significant increase in the mean urinary metabolic ratio (MR) of dextromethorphan/dextrorphan and in the mean mephenytoin S/R ratio (S/R) was seen with the fluvoxamine and fluoxetine treatment. The mean MR increased from 0.13 to 0.27 (P<0.01) with fluoxetine and from 0.34 to 0.84 with fluvoxamine (P<0.05). The (dextromethorphan) 'extensive metabolizer' phenotype switched to the 'poor metabolizer' phenotype in six patients by the 10-day fluoxetine treatment, and in two patients by the fluvoxamine treatment. The mean S/R increased from 0.24 to 0.34 (P<0.05) with fluoxetine, and from 0.33 to 0.58 (P<0.002) with fluvoxamine. These results are in agreement with the observed modification of TCA plasma levels after the SSRI association. During fluvoxamine treatment, amitriptyline and clomipramine plasma levels (P<0.06 both) tendentially increased, and those of demethylclomiprarnine decreased (P<0.06). Fluoxetine addition lead to a significant increase (P<0.02) of the desmethylclomipramine plasma levels. Fluvoxamine induced a moderate augmentation of the plasma levels of haloperidol and its reduced metabolite and no change in the plasma levels of cyamemazine and levomepromazine. But patients treated with neuroleptics are to few to draw any firm conclusion. This study suggests, that fluoxetine and fluvoxamine differ in their interaction with the metabolism of some other basic psychotropic drugs, by a mechanism which implies CYP2D6 and CYPmeph and possibly other isoformes of cytochrome P-450. Moreover, the interactions produced varied with the TCA prescribed.

Adult↗
PubMed2005

Are the effects of the antidepressants amitriptyline, maprotiline, and fluoxetine on inhibitory avoidance state-dependent?

State-dependent learning (SDL) is a phenomenon in which the retrieval of newly acquired information is possible if the subject is in the same physiological state as during the encoding phase. SDL makes it possible to separate the effects of drugs per se on learning from the effects due to changes in drug state during the task. The present work was designed to investigate whether the antidepressants amitriptyline (30 mg/kg), maprotiline (25 mg/kg), and fluoxetine (15 mg/kg) produce SDL of the inhibitory avoidance conditioning in male and female CD1 mice. In three separate experiments, independent groups were used for each pharmacological treatment and for each sex using a 2 x 2 experimental design. The results do not show SDL in any of the drugs. In the case of amitriptilyline, the data can be attributed to a memorization deficit, while the maprotiline results are interpreted as simultaneously influenced by memorization deficit and performance facilitation due to motor impairment. Fluoxetine treatment did not produce any deteriorating effect on the conditioning. Drugs had some different effects on the performance of males and females, males showing a slightly higher deterioration than females with administration of amitriptyline and maprotiline. This study shows that these antidepressants affect the acquisition/consolidation but not the retrieval process in the inhibitory avoidance learning.

Amitriptyline↗
PubMed2005

Amitriptyline prevents thermal hyperalgesia and modifications in rat spinal cord GABA(B) receptor expression and function in an animal model of neuropathic pain.

Using an animal model of neuropathic pain, behavioral and biochemical experiments were performed to assess the effects of this condition on pain threshold and GABA(B) receptor sensitivity and subunit gene expression in the rat lumbar spinal cord. The results indicate that partial sciatic nerve ligation decreases thermal and mechanical pain withdrawal latencies, and increases baclofen-stimulated [35S]GTPgammaS binding and GABA(B) receptor subunit gene expression in the rat lumbar spinal cord, suggesting that neuropathic pain may be due, in part, to a deficiency in GABAergic transmission. The experiments also demonstrate that daily administration (10 mg/kg, i.p.) of amitriptyline, a tricyclic antidepressant used for the treatment of neuropathic pain, for 1 week after surgery prevents the decline in thermal pain threshold, the increase in GABA(B2) gene expression, and development of increased GABA(B) receptor function in spinal cord resulting from nerve damage. These findings indicate that the efficacy of amitriptyline as a treatment for neuropathic pain may be related to an ability to maintain spinal cord GABA(B) receptor activity.

Amitriptyline↗
PubMed2005

Effects of amitriptyline and gabapentin on bilateral hyperalgesia observed in an animal model of unilateral axotomy.

Nociceptive responses in an animal model of peripheral nerve injury were studied. The left common sciatic nerve was exposed, tightly ligated at two locations and transected between the ligatures. A bilateral decrease in the nociceptive threshold to mechanical stimulation was observed within 3 h after the operation. The skin of the lateral dorsal part of the injured paw was hypoalgesic, while the medial dorsal paw innervated by the intact saphenous nerve and the contralateral dorsal paw exhibited hyperalgesia. Amitriptyline, an antidepressant, at 25, 50 and 100 mg/kg per day, p.o., and gabapentin, an anticonvulsant, at 30, 100 and 300 mg/kg per day, p.o., significantly inhibited the decrease in the mechanical nociceptive threshold in the injured and uninjured paws. The effects of amitriptyline at 25 and 50 mg/kg were evident at doses that did not cause neurologic deficits as assessed by the inclined screen test. Indomethacin, a cyclooxygenase inhibitor, and morphine (except at the highest dose of 30 mg/kg, s.c.) showed no analgesic effects in this model. The tail-flick latency was also significantly decreased compared with intact rats. Similar bilateral hyperalgesia was observed when axotomy was performed using silk thread instead of chromic gut. When this axotomy model was applied to mice, the nociceptive thresholds in both paws immediately showed a significant decrease in the same manner as in rats. The bilateral and systemic hyperalgesia observed in this axotomy model, which resembles the clinical features of chronic neuropathic pain, suggests the involvement of the central nervous system in the maintenance of the chronic pain state.

Amines↗
PubMed2005

Neuroendocrine (HPA axis) and clinical correlates during fluvoxamine and amitriptyline treatment.

The effect of amitriptyline on hypothalamic-pituitary-adrenocortical (HPA) axis activity was compared with that of fluvoxamine in 38 patients suffering from DMS-IV major depressive disorder. Basal plasma adrenocorticotropic hormone and cortisol levels were determined in the so-called "observation window" of an hour (08:00-09:00 h), and cortisol levels were determined again at 20:00 h. Clinical and biochemical assessments were performed before therapy (T0), at day 14 (T14), and at day 42 (T42) of the course of antidepressant treatment. At T0, neuroendocrine parameters did not differ in patients from those in controls, except for the ratio between cortisol levels at 20:00 h and the mean level of the "window" (ratio F20/F8), which was significantly higher, suggesting a dysregulation of the circadian pattern of cortisol. Although a decrease in the ratio F20/F8 was already apparent at T14 of both treatments, the repeated measures analysis of variance failed to demonstrate a significant variation with time (T0, T14, and T42) and with treatment (amitriptyline and fluvoxamine) for any hormonal measure. At T42, both treated groups showed a similar level of clinical improvement. Our results did not demonstrate any effect of antidepressant therapy on the cortisol circadian rhythm abnormality.

Adrenocorticotropic Hormone↗
PubMed2005

Amitriptyline and nortriptyline serum determination by micellar liquid chromatography.

INTRODUCTION: Amitriptyline and nortriptyline are tricyclic antidepressants which act by enhancing the actions of norepinephrine and serotonin caused by blocking the re-uptake of various neurotransmitters at the neuronal membrane. A micellar liquid chromatographic procedure was developed to determine these drugs in serum samples for use in clinical monitoring. METHODS: The chromatographic determination of these highly hydrophobic substances was carried out using a 0.15 M SDS-6% (v/v) pentanol buffered at pH 7, in a C18 column, and electrochemical detection at 650 mV. The flow-rate was 1.5 mL/min. The analysis time was 14 min. RESULTS: The limits of detection (ng/mL) in serum were 0.25 and 0.31 for amitriptyline and nortriptyline, respectively. Repeatability and intermediate precision were evaluated at three different concentrations in serum samples. DISCUSSION: Untreated serum samples were injected directly into the HPLC system after filtration, leading to be a simple procedure that can be applied in routine analyses for Therapeutic Drug Monitoring.

Amitriptyline↗
PubMed2000

In vitro studies of the phototoxic potential of the antidepressant drugs amitriptyline and imipramine.

Amitriptyline and imipramine, two tricyclic antidepressant drugs, have been studied to evaluate their phototoxic potential using various models. Reactive oxygen species production was investigated. A negligible production of singlet oxygen was observed for both compounds whereas a significant production of superoxide anion was noted for amitriptyline in particular. Moderate red blood cell lysis under UVA light (365 nm) was induced in the presence of the two drugs at a concentration of 50 microM. Cellular phototoxicity was investigated on a murine fibroblast cell line (3T3). The two drugs were phototoxic causing cell death at a concentration of 100 microM and a UVA dose in the range of 3.3-6.6 J/cm2. Furthermore, the two drugs photosensitized the peroxidation of linoleic acid, as monitored by the formation of dienic hydroperoxides. The presence of BHA and GSH, two free radical scavengers, significantly reduced the lipid oxidation photoinduced by the drugs, suggesting a predominant involvement of radical species. Finally, the involvement of nucleic acids in the phototoxicity mechanism was also investigated using a pBR322 plasmid DNA as a model.

Amitriptyline↗
PubMed1978

Ion-pair liquid chromatography of amitriptyline and metabolites in plasma.

A method is described for the determination of amitriptyline and nortriptyline in the plasma of patients during treatment. The method is based on liquid chromatography of the amines as ion-pairs with perchlorate. The separation column is packed with silica gel, and a mixture of diisopropyl ether, dichloromethane, methanol and water containing the counter ion is used as eluent. High efficacy and stability of the system is achieved. The separation of metabolites is demonstrated. The cis- and trans-10-hydroxy isomers of amitriptyline and nortriptyline are easily resolved with this chromatographic system.

Amitriptyline↗
PubMed1984

Amitriptyline and its basic metabolites determined in plasma by gas chromatography.

Gas chromatography was used to determine plasma levels of amitriptyline, nortriptyline and their 10-hydroxy derivatives after conversion to the dehydro compounds by heating with acid. The primary amine 10-hydroxydesmethylnortriptyline is also dehydrated and the dehydro compound coincides on the chromatogram with dehydronortriptyline. Treatment of the extract with salicylaldehyde selectively removed the primary amine, which was determined by difference. Cis- and trans-hydroxydesmethylnortriptyline were isolated from urine by thin-layer chromatography and used to standardize the estimation. The stability of all the metabolites in plasma was investigated. Results are given for hydroxydesmethylnortriptyline levels in the plasma of 41 patients treated with amitriptyline.

Amines↗
PubMed1989

Use of amitriptyline in the treatment of interstitial cystitis.

A total of 25 patients with interstitial cystitis who had failed standard therapy with hydrodistension of the bladder during anesthesia and intravesical dimethyl sulfoxide instillation underwent treatment with the tricyclic antidepressant amitriptyline. The initial dosage of 25 mg. before bed was increased gradually during a 3-week period to 75 mg. at bedtime. Of the patients 20 were able to tolerate the medication for a minimum of 3 weeks and could be evaluated for response. A significant improvement was noted in pain and daytime frequency. Of 9 patients 8 experienced relief of dyspareunia and 11 of 19 reported diminished urinary urgency. Eight patients have experienced virtual total remission of symptoms and have been on the drug for 4 to 28 months. It appears reasonable to consider the use of amitriptyline in patients with interstitial cystitis refractory to standard therapy.

Adult↗
PubMedDate not supplied

The efficacy of amitriptyline and acetaminophen in the management of acute low back pain.

Thirty-nine patients with acute low back pain were treated with amitriptyline (150 mg/d) or acetaminophen (2,000 mg/d) in a controlled double-blind design for 5 weeks. Both groups revealed mild depression, normal coping, and increased anxiety at the beginning, with significant improvement in anxiety state and pain at the end of treatment. A repeated measures analysis of variance demonstrated that amitriptyline was more effective than acetaminophen in reducing pain intensity from the second week of treatment. Age and depression were the only significant pretreatment predictors of posttreatment pain. The study evaluates the significance of these findings.

Acetaminophen↗
PubMed1978

Amitriptyline plasma-concentration and clinical effect. A World Health Organisation Collaborative Study.

54 patients in five centres participated in a study of the relationship between steady-state plasma-levels of amitriptyline (AT) and its active metabolite nortriptyline (NT) and therapeutic response. The participants were inpatients who, after a 7-12 day period of assessment, were rated greater than or equal to 16 on the Hamilton rating scale for depression. They were given 75 mg of amitriptyline for 3 days and then 150 mg daily for an active-treatment period of 6 weeks. Clinical ratings and plasma-samples were obtained at baseline then at 2, 4, and 6 weeks after starting therapy. Contrary to the findings of three previous trials, no important correlations were found between steady-state plasma-levels and therapeutic outcome or corrected side-effects. Corrected side-effects correlated negatively with therapeutic outcome. There seems little advantage in routine monitoring of AT and NT, since variations in plasma-levels do not account for the considerable variation in therapeutic outcome.

Adult↗