Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “NORTRIPTYLINE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,243 records · Page 69Linked to original sources
PubMed1988

Antidepressive effect of amitriptyline treatment with plasma drug levels controlled within three different ranges.

Seventy-four depressed patients were treated with amitriptyline for 4-6 weeks. Their doses were individually adjusted to maintain the sum of the plasma levels of amitriptyline (AT) and nortriptyline (NT) within one of three different ranges, randomly allocated. Allowance was made for individual plasma binding of the drugs. In the 50 patients between 25 and 65 years of age, the antidepressive response at low plasma drug levels was somewhat poorer than at medium or high levels, which were equally effective. In this age group an association was found between outcome and the individual rate of AT metabolism, expressed as "reciprocal clearance" (RC), the steady-state plasma concentration of AT plus NT divided by the daily AT dose. Good antidepressive outcome was associated with high RC. The implications of these findings for patient treatment and for the interpretation of other studies are discussed. The 18 patients between 65 and 80 years of age showed no significant differences between the effectiveness of treatment at different plasma drug levels, and no significant associations between outcome and RC.

Aged↗
PubMedDate not supplied

Modulation by antidepressant drugs of CNS postsynaptic alpha 2-adrenoceptors mediating mydriasis in the rat.

The modulation of central postsynaptic alpha 2-adrenoceptors mediating mydriasis in the pentobarbitone-anaesthetized rat was studied after the acute and short/long-term administration of antidepressant treatments (drugs, electroshock). The acute administration of cyclic antidepressant drugs (2.5 mg/kg, i.v.) resulted in different mydriatic effects (amitriptyline greater than protriptyline approximately imipramine greater than clomipramine greater than nortriptyline greater than desipramine approximately maprotiline) which were attenuated (17-55%) by idazoxan (1 mg/kg, i.v., 5 min) and reserpine (5 mg/kg, s.c., 18 h) indicating that, besides the well-known anticholinergic properties of some of these drugs, their mydriatic effects are due in part to activation of alpha 2-adrenoceptors (through endogenous noradrenaline). In contrast, the long-term (7-21 days) but not the short-term (1-4 days) administration of cyclic antidepressant drugs (2.5-10 mg/kg, i.p.), MAO inhibitors (1 mg/kg, i.p.), lithium (20 mg/kg, i.p.) and electroshock (150 mA, 63 Hz, 8 ms during 300 ms) resulted in dose- and time-dependent reductions of the dose-pupillary response curve for clonidine (ED50 increased 1.2-2.0-fold; Emax decreased by 9-29%) which indicated desensitization of postsynaptic alpha 2-adrenoceptors. In line with these findings, treatment for 7 days with clonidine (0.1-1 mg/kg, i.p.) or idazoxan (3-10 mg/kg, i.p.) led to an opposite modulation (down- and up-regulation) of the dose-pupillary response curve for clonidine. The main results demonstrate that cyclic antidepressant drugs, through indirect mechanisms which involve endogenous noradrenaline, can modulate the sensitivity of brain postsynaptic alpha 2-adrenoceptors mediating mydriasis in the rat.

Anesthesia↗
PubMed1986

Clonidine--induced behavioural despair in mice: reversal by antidepressants.

The effects of various alpha 2 adrenoceptor agonists on forced swimming-induced despair behaviour were studied in mice. Clonidine, B-HT 920 and guanfacine significantly prolonged the total immobility duration. Clonidine-induced behavioural despair was antagonized by prior treatment with yohimbine. The tricyclic antidepressants imipramine, desipramine, trimipramine, amitriptyline, nortriptyline and doxepin, the MAO inhibitor tranylcypromine, and the antimanic agent lithium reversed clonidine-induced behavioural despair. Chronic treatment with imipramine evoked more pronounced reversal as compared to acute treatment. Amphetamine, a psychostimulant, inhibited clonidine-induced enhancement of immobility duration but diazepam, a skeletal muscle relaxant was without any effect. On the other hand, adenosine showed potentiation of the submaximal response of clonidine. These observations suggest that clonidine-induced behavioural despair is probably mediated through its presynaptic action on alpha 2 adrenoceptors, resulting in reduced central noradrenergic outflow. The present data proposes a simple test system to induce depression-like syndrome in animals, sensitive to antidepressant therapy.

Animals↗
PubMed1993

Minor and clinically non-significant interaction between toloxatone and amitriptyline.

The possibility of a pharmacokinetic interaction between amitriptyline and toloxatone (a new MAOI-A) has been studied in 17 depressed in-patients. Amitriptyline and its demethylated and hydroxylated metabolites in blood and urine were measured at steady state after the administration of amitriptyline with and without toloxatone in steady state. The metabolic status of patients was determined using the dextromethorphan phenotyping test. There was only a minor pharmacokinetic interaction between amitriptyline (AMT) and toloxatone, with a small increase in the AMT/NT (nortriptyline) plasma ratio: 0.68 before and 0.78 after toloxatone. The urinary excretion and plasma levels of AMT and its metabolites were not affected by the co-therapy. Three of the patients were poor metabolisers, but this did not predict the magnitude of the drug interaction. The interaction does not justify plasma level monitoring of amitriptyline as the change in pharmacokinetics was so small.

Adult↗
PubMed1993

Tricyclic antidepressant plasma levels after augmentation with citalopram: a case study.

In a depressed patient, the addition of citalopram 40-60 mg per day to treatment with amitriptyline 75 mg per day had no effect on the plasma levels of amitriptyline and nortriptyline, but it led to clinical improvement without the appearance of adverse effects. This and similar findings in four other patients comedicated with citalopram and amitriptyline (2 patients), clomipramine or maprotiline suggest that citalopram differs from other selective serotonin reuptake inhibitors, such as fluvoxamine and fluoxetine, which have been shown to increase tricyclic antidepressant plasma levels.

Antidepressive Agents, Tricyclic↗
PubMed1986

Amitriptyline and oxaprotiline in the treatment of hospitalized depressive patients. Clinical aspects, psychophysiology, and drug plasma levels.

Amitriptyline (AT) and the noradrenaline reuptake inhibiting antidepressant oxaprotiline (OT = hydroxymaprotiline) were compared in 59 primary depressive inpatients in a 4-week double blind parallel group design. In the Hamilton Depression Rating Scale and 2 self-rating scales AT proved to be more efficient than OT, mainly with respect to disturbances of appetite and sleep. Agitated patients receiving OT needed more additional tranquilizing medication. The number of side-effects did not differ. Both drugs increased heart rate and skin resistance level (SRL) to about the same degree and did not influence the number of spontaneous fluctuations of SRL, habituation of SRL orienting responses (OR), frequencies of respiration and blinking. Salivation was temporarily more impaired by AT. All physiological variables differed between patients and 30 healthy controls during the whole 4-week trial. Clinical outcome showed a linear relation to OT plasma levels. For AT a therapeutic window was confirmed for concentrations of AT and its metabolite nortriptyline between 125 and 200 ng/ml. Patients whose SRL-OR habituated rapidly had a better outcome than slow habituators. Urinary excretion of 3-methoxy-4-hydroxyphenylglycol was lower in patients than in controls but could not predict outcome with either drug.

Amitriptyline↗
PubMed1976

On the classification of antidepressant drugs.

Clinical, pharmacologic, and biochemical profiles of antidepressant drugs have been analyzed statistically. A method derived from multivariate statistics separates mere drug potency from the spectral information contained in the profiles. The dimensionality of the spectra is also reduced and this results in a diagram of associations and dissociations between the antidepressants and their scales of observation. The spectra of antidepressants show three poles which have been labeled as D (desipraminelike), A (amitriptylinelike), and M (MAOI). Clinical spectra agree better between one another than various pharmacologic spectra do. Monoamine oxidase inhibitors are readily differentiated from the tricyclic compounds. The latter appear in the sequence: desipramine, nortriptyline, imipramine, and amitriptyline. This sequence can also be reproduced from biochemical spectra of central and peripheral blockade of norepinephrine and serotonin reuptake.

Affect↗
PubMed1984

Comparative animal studies on cardiovascular toxicity of tri- and tetracyclic antidepressants and citalopram; relation to drug plasma levels.

The aim of the present study was to compare cardiovascular and/or cardiotoxic effects of eight anti-depressants (imipramine, chlorimipramine, amitriptyline, nortriptyline , doxepin, maprotiline, mianserin and citalopram) in anaesthetized cats after oral dosing and in conscious rabbits after intravenous infusion. In the cats drug plasma levels were determined as well. When estimated from ECG recordings, citalopram and chlorimipramine in particular, but also mianserin, appeared less cardiotoxic than the other drugs tested. The cardiovascular effects seen in the cats were with few exceptions identical for all the drugs tested but not seen at the same dose (concentration). Safety margins were defined as minimal doses or plasma levels when ECG changes (conduction or rhythm) or cardiovascular effects (+/- 10% change of initial value in a series of parameters) occurred in experimental animals divided by maximal therapeutic dose or mean plasma levels in patients. From comparisons of the safety margins it is concluded that except for citalopram and mianserin (safety margins 80 and 18 respectively in cats and greater than 15 in rabbits) all the other drugs tested (safety margins less than or equal to 9) have a cardiotoxic potential. The probability that cardiovascular side effects may occur is less pronounced for citalopram (safety margins 10-32) than for all the other drugs tested (safety margins ranging from 0.1 to less than 5).

Anesthesia↗
PubMed1981

Amitriptyline pharmacokinetics. Single doses of Lentizol compared with ordinary amitriptyline tablets.

Two separate single doses of Lentizol (W. R. Warner, Pontypool, U.K.), a sustained-release preparation of amitriptyline (AT) were taken by each of six healthy subjects. Plasma concentrations of AT and of nortriptyline (NT) were determined at intervals over a period of 48 or 72 h. Faeces were collected and their drug content measured. Results were compared with those obtained when the same subjects took ordinary AT tablets. AT was found in the faeces after the ingestion of Lentizol or of ordinary AT tablets. However, after NT tablets negligible amounts of NT appeared in the faeces. AT was sometimes absorbed slowly from Lentizol, but on other occasions it was absorbed as rapidly as from ordinary tablets. Plasma levels of AT 24 h after the dose were usually not higher after Lentizol than after an equal dose of ordinary tablets. The systemic bioavailability of Lentizol as judged by areas under the plasma concentration-time curves, both for AT and for the NT formed metabolically, was on average lower than that of the ordinary tablets. However, the amounts of AT found in the faeces were not large enough to account for the AT area reduction by simple failure of absorption. Possible explanations of the discrepancy are discussed.

Amitriptyline↗
PubMed1985

Cardiovascular effects of amitriptyline in the treatment of elderly depressed patients.

Thirteen elderly depressed patients (age 60-82 years) were treated for 5 weeks with a fixed dose of amitriptyline 100 mg (sustained release preparation). In all patients the sum of concentrations of amitriptyline and nortriptyline exceeded 130 micrograms/l, which is the recommended plasma level. Cardiovascular side effects were recorded by monitoring heart rate, blood pressure, standard ECG and systolic time intervals. During treatment, a transient increase in the supine heart rate was observed without significant changes in the supine blood pressure. The orthostatic drop in blood pressure was markedly increased during treatment without a compensatory increase in heart rate, and these changes remained significant during the whole investigational period. PQ and QRS were significantly increased during treatment, and significant changes in the systolic time intervals were found indicating impairment of myocardial conduction and contractility. In three patients medication was discontinued due to cardiovascular side effects.

Aged↗
PubMed1980

Stimulus properties of antidepressants in the rat.

Various doses of bupropion HCl (Wellbatrin) (5, 10, and 20 mg/kg), a new phenylaminoketone antidepressant, were employed as cues in a two-lever operant discrimination from saline control injections in rats on an FR10 schedule of food reinforcement. Subjects reached and maintained a high level of discrimination in the O vs 20 mg/kg bupropion stimulus condition but not at the lower doses. In generalization testing, the following compounds produced dose-related responding on the bupropion lever: viloxazine, nomifensine, caffeine, d-amphetamine, cocaine, methylphenidate, and benzylpiperazine. Drugs that failed to show dose-related generalization included phenethylamine, thyrotropin-releasing hormone, imipramine, nortriptyline, amitriptyline, desipramine, mianserin, chlordiazepoxide, diazepam, scopolamine, phenobarbital, and morphine. With the important exception of viloxazine, the generalization profile of bupropion seems to reflect its previously reported locomotor stimulant effects in the rat rather than its antidepressant activity and suggests that species differences exist between man and rat with regard to the pharmacologic activity of this new antidepressant.

Animals↗
PubMed1982

Time course of plasma drug levels during once-daily oral administration of clomipramine.

Fourteen depressed in-patients were treated with 150 mg clomipramine (CLO) daily, given as one oral dose. Using a gas-chromatographic method, concentrations of CLO and desmethyl clomipramine (DMCLO) were determined in plasma samples taken at frequent intervals during 24 h. The plasma level of each compound 12 h after the dose correlated well with the average value in the same patient, calculated over the whole 24-h period. Levels at other times gave poorer correlations, and at 24 h it was particularly poor. Plasma DMCLO concentrations were usually maximum 4-6 h after the dose. The ratios of maximum to minimum levels averaged only 1.31 +/- 0.15 SD. Peak CLO levels occurred 3 or 4 h after the dose. Maximum; minimum ratios averaged 2.72 +/- 0.73 SD, contrasting with the much smaller fluctuations of plasma nortriptyline (NT) levels observed in patients given this drug once daily. The difference is not due to a shorter half-life of CLO, but to the absorption and/or distribution behaviour of the two drugs. Although not fully understood, this difference between tertiary and secondary amines appears to hold generally among the tricyclic antidepressants.

Administration, Oral↗
PubMed1984

Determination of free fractions of tricyclic antidepressants.

The plasma protein binding of amitriptyline, imipramine, clomipramine, and their primary demethylated metabolites were studied by means of a method combining dialysis and gas chromatography. Equilibrium in dialysis of serum containing amitriptyline and its metabolite nortriptyline was attained in about 0.5 h with the drug dissolved in the serum compartment, and in about 2 h with the drug passing from the buffer to the serum compartment. The calculation of free fractions was influenced by variations with dialysis time in the volumes of serum and buffer. Increase of pH in serum increased the protein binding of the weakly basic drugs studied, and made the Donnan distribution effects more pronounced. At pH 7.4, the Donnan effect was negligible. Binding parameters for the 6 tricyclic antidepressant substances studied were estimated for the binding to alpha 1-acid glycoprotein and for total binding in serum. For alpha 1-acid glycoprotein, the k-values ranged from 1 X 10(5) to 8 X 10(5) M-1, and for pooled serum from 0.4 X 10(5) to 8 X 10(5) M-1. The determined number of binding sites on the alpha 1-acid glycoprotein was, on average 0.87 for the 6 substances. In serum, the binding capacity was 2-14 times the concentration of alpha 1-acid glycoprotein.

Antidepressive Agents, Tricyclic↗
PubMed1981

The noradrenaline receptor coupled adenylate cyclase system in brain. Lack of modification by changes in the availability of serotonin.

The present studies were undertaken to ascertain whether or not an alteration in the availability of serotonin (5HT) can modify central noradrenergic function at the level of the noradrenaline (NA) receptor coupled adenylate cyclase system in brain. The chronic but not acute administration of the 5HT uptake inhibitors amitriptyline and chlorimipramine reduced the sensitivity of the cyclic AMP generating system to NA in the limbic forebrain. This subsensitivity was linked to a decrease in the Bmax value of beta-adrenergic binding sites without appreciable changes in the Kd values, as assessed by specific 3H-dihydroalprenolol binding. The specific 5HT uptake inhibitor fluoxetine did not change either the responsiveness of the cyclic AMP generating system to NA or the density of beta-adrenergic receptor sites. Raphé lesions which selectively reduced the level of 5HT also did not cause any changes in the neurohormonal responsiveness or the density of beta-adrenergic receptor sites. In contrast, medial forebrain bundle lesions which reduced the levels of both 5HT and catecholamines (NA and dopamine) in the forebrain, increased the responsiveness of the cyclic AMP generating system to NA. It can thus be concluded that a selective change in the availability of 5HT per se does not modify noradrenergic receptor function at the level of the NA receptor coupled adenylate cyclase system. The subsensitivity of the noradrenergic receptor system developed following amitriptyline and chlorimipramine may in all likelihood be due to the in vivo conversion to the secondary amines, nortriptyline and desmethylchlorimipramine respectively. These secondary amine metabolites are potent inhibitors of the NA reuptake and consequently could be responsible for the demonstrated in vivo down-regulation of central adrenergic receptor function (homospecific down-regulation).

Adenylyl Cyclases↗
PubMed1976

The effect of tricyclic antidepressant drugs on the heart.

The effects on the heart rate and ECG of anaesthetised guines-pigs of amitriptyline, doxepin, imipramine and nortiptyline infused at 1.0 mg/kg/min until death were observed. In addition an in vitro study on guinea-pig atria was performed on the chronotropic and inotropic effects of these drugs and of desmethylimipramine and protriptyline at a concentration of 10(-5) M. The effect of sodium bicarbonate (3 mEq/kg i.v.) and propranolol (0.01--0.2 mg/kg i.v.) on amitriptyline and doxepin induced ECG changes was also assessed. A difference in the cardiac effects of the in vivo and in vitro model was observed. Guinea-pigs infused with doxepin survived significantly longer than those infused with amitriptyline, imipramine or nortriptyline. No statistically significant difference was found between the tricyclic drugs with respect to onset of widening of the QRS complex, increased PR and QT intervals. In the spontaneously beating atrial preparation doxepin was the most potent cardio-depressant. Sodium bicarbonate had no effect on arrhythmias induced by tricyclics, while propranolol, apart from the bradycardia induced, was without beneficial effect on the ECG. The guinea-pig provides a good model for studying the arrhythmogenic actions of tricyclic antidepressants.

Animals↗
PubMed1977

Comparative bioavailability of a sustained release preparation of amitriptyline and conventional tablets.

A sustained release preparation of amitriptyline has been compared with conventional tablets in eight healthy human volunteers. The tablet produced a distinct peak in serum concentration shortly after administration, whereas the sustained release preparation caused a slow rise to a plateau. The maximum serum concentration and the time of its occurrence differed significantly between the two preparations. The differences between the serum concentration curves of the two preparations can be explained on the basis of a two compartment model of amitriptyline pharmacokinetics and from a difference in the absorption rate. The similar clinical effect obtained with a lower daily dose of the sustained release preparation than of the tablet cannot be accounted for in terms of pharmacokinetics. It is possible that a single evening dose of sustained release amitriptyline gives a more appropriate serum concentration profile of amitriptyline and its active metabolite nortriptyline than a conventional tablet taken three times a day.

Adult↗
PubMed1984

Metabolism of amitriptyline in patients with chronic renal failure.

The metabolism of amitriptyline (AMT) has been studied in two groups of depressed in-patients on long term AMT therapy: 11 patients with no other major disease and 8 patients with chronic renal failure, who were being dialysed. The patients with renal insufficiency had decreased concentrations of AMT, nortriptyline (NT) and their unconjugated hydroxymetabolites compared to patients with normal kidney function. The plasma levels of conjugated products were extremely high in the uraemics. The latter metabolites are probably inert. The reduced concentration of unconjugated hydroxymetabolites , which are active compounds, may decrease the clinical effectiveness of the drug.

Adult↗
PubMed1982

Overdosage of antidepressants: clinical and pharmacokinetic aspects.

Twenty-nine cases of self-poisoning with antidepressants (amitriptyline, imipramine, clomipramine, maprotiline, doxepine, nortriptyline, opipramol) were examined by frequent observation of CNS effects, heart rate, blood pressure and standard ECG, 24h-ECG-monitoring, measurement of systolic time intervals, EEG recordings and frequent measurement of serum levels of antidepressants and primary metabolites. None of the patients died. Maximum total serum antidepressant level (parent compound + desmethyl metabolite) ranged from 20 to 2200 micrograms/l, with concentrations above 500 micrograms/l in 11 cases. The serum amitriptyline concentration remained high for 3-4 days in some of the severely intoxicated patients and the decay curves were compatible with partly saturated elimination. A degree of unconsciousness and the occurrence of excitation and hallucinations were generally seen in cases with total serum antidepressant levels above 500 micrograms/l. Grand mal seizures occurred more frequently at high antidepressant levels, but could not be predicted from the EEG recordings. Increased heart rate and prolonged QRS- and QTc-intervals were significantly correlated with the total serum antidepressant level. 24 h-ECG-monitoring revealed no serious arrhythmias or instances of heart block. Hypotension was only seen initially in few patients. Systolic time interval measurements showed changes suggesting impaired myocardial performance (elevated PEP/LVET ratio) at intermediate (60-500 micrograms/l) but not high (greater than 500 micrograms/l) total serum antidepressant levels. Measurement of serum concentration in antidepressant intoxication is important for identification of patients with high serum levels and the corresponding risk of developing toxic reactions, and to exclude patients with a low concentration who do not require intensive observation.

Adult↗