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At least 19 recordsLinked to original sources
PubMed1979

Gas chromatographic determination of amitriptyline, nortriptyline and perphenazine in plasma of schizophrenic patients after administration of the combination of amitriptyline with perphenazine.

A specific and sensitive gas-chromatographic technique using a common extraction procedure for the quantitative determination of amitriptyline, endogenous nortriptyline and perphenazine in plasma of schizophrenic patients receiving therapeutic doses of a combination of amitriptyline and perphenazine (Etrafon) has been developed. The lower limits of detection are 20 ng/ml for amitriptyline, 1 ng/ml for nortriptyline and 5 ng/ml for perphenazine. Amitriptyline is estimated with a flame ionization detector. Nortriptyline is quantitated using an electron capture detector after converting it to its heptafluorobutyryl derivative by reaction with the appropriate anhydride. Perphenazine is also determined using an electron capture detector after forming its stable, trimethylsilyl derivative by reaction with N,O-bis-(trimethylsilyl)-acetamide. In individual patients, the steady-state plasma levels ranged from 44 to 215 ng/ml for amitriptyline, from 49 to 270 ng/ml for nortriptyline and from less than 5 to 20 ng/ml for perphenazine. Steady-state plasma levels data on amitriptyline, nortriptyline and perphenazine in 23 patients treated with Etrafon are presented.

Adult↗
PubMed1978

Comparative trial of amitriptyline-N-oxide and amitriptyline in the treatment of out-patients with depressive syndromes.

Amitriptyline-N-oxide and amitriptyline were compared double-blind in a material of out-patients with depressive syndromes, 21 and 22 patients respectively. Both drugs had a good antidepressant effect. The globally rated effect was equal. The effect upon the various depressive symptoms was equal. Definite reversal of depression occurred somewhat earlier on amitriptyline-N-oxide on which side effects were also less marked, but those of an anticholinergic and of a sedative nature. No orthostatic reaction, nor any effect upon blood status or liver function was observed. Amitriptyline-N-oxide appears to show a tendency to a somewhat more rapid onset of effect and less side effects.

Adult↗
PubMed1979

A method for the determination of amitriptyline and its metabolites nortriptyline, 10-hydroxyamitriptyline, and 10-hydroxynortriptyline in human plasma using stable isotope dilution and gas chromatography-chemical ionization mass spectrometry (GC-CIMS).

A gas chromatography--mass spectrometry (GC-MS) method has been developed to measure amitriptyline and its metabolites nortriptyline, 10-hydroxyamitriptyline, and 10-hydroxynortriptyline in human plasma. Deuterated analogs of each compound were synthesized as internal standards. Isobutane was used as both gas chromatography (GC) carrier gas and chemical ionization (CI) reagent gas. In order to obtain compounds with satisfactory GC and mass spectrometry (MS) properties, the two alcohol metabolites were dehydrated without loss of label during sample preparation. Selective ion monitoring of the MH+ ions of the protio- and deuterio- compounds gave ion ratios which were converted to plasma concentrations using standard curves. For amitriptyline and nortriptyline, which are assayed using multiple deuterated analogs as internal standards, the curves are straight lines. For 10-hydroxyamitriptyline and 10-hydroxynortriptyline, which are assayed using monodeuterated analogs as internal standards, the curves are nonlinear and are analyzed using an iterative computer procedure. Assay sensitivity is 0.5 ng/ml for amitriptyline, nortriptyline, and 10-hydroxyamitriptyline and 1 ng/ml for 10-hydroxynortriptyline. Assay precision and accuracy in terms of percent error are both less than 5%. Following oral administration of a single 75-mg dose of amitriptyline to two subjects, the mean plasma levels of amitriptyline, nortriptyline, 10-hydroxyamitriptyline, conjugated 10-hydroxyamitriptyline, 10-hydroxynortriptyline, and conjugated 10-hydroxynortriptyline were 36, 8, 10, 66, 16, and 46 ng/ml, respectively, at 2 hr after dosing and 3, 4, 0.5, 1, 6, and 17 ng/ml, respectively, at 72 hr after dosing. Analyses of plasma samples from 12 subjects who had been receiving 50 mg amitriptyline therapy three times a day for an average +/- SD of 32 +/- 5 days gave a mean concentration of 81 +/- 40 ng/ml for amitriptyline, 71 +/- 57 ng/ml for nortriptyline, 12 +/- 5 ng/ml for 10-hydroxyamitriptyline, 91 +/- 30 ng/ml for conjugated 10-hydroxyamitriptyline, 82 +/- 27 ng/ml for 10-hydroxynortriptyline, and 176 +/- 64 ng/ml for conjugated 10-hydroxynortriptyline.

Amitriptyline↗
PubMed1975

Noxiptilin (Agedal)--a new tricyclic antidepressant with a faster onset of action? A double-blind, multicentre comparison with amitriptyline.

Five psychiatric hospitals in Norway took part in this double blind clinical trial, in which noxiptilin (Agedal) was compared with amitriptyline in hospitalized patients with primary depressive illness. According to total randomization, each patient received either noxiptilin or amitriptyline in semiflexible dosage, usually to a maximum dialy dose of 200-250 mg, for at least three, and possibly six weeks. Thirty patients received noxiptilin and 32 received amitriptyline for at least three weeks. The "total" improvement was assessed in two different ways: 1) By direct global assessment; according to this method, there was a non-significant tendency towards greater improvement on amitriptyline after three and sex weeks, in female and male patients alike. 2) By percentage reduction in total score on Hamilton's rating scale for depression; according to this method, there was a significantly greater improvement on noxiptilin after one week in female but not in male patients. After 2, 3 and 6 weeks there were no significant differences. Thus, this trial seems to support earlier claims that noxiptilin has a faster onset of action than amitriptyline. The two drugs did not differ significantly in their effect on any single symptom, nor in their effect on different types of depression. Both drugs had a better effect in patients with duration of present illness less than three months, than in patients with a duration longer than three months. Noxiptilin had a significantly better effect than amitriptyline in patients with insidious onset of present illness, whereas there was a strong (but non-significant) tendency for a better effect of amitriptyline in patients with a more acute onset of illness. No satisfactory explanation can be offered for this unexpected finding.

Adult↗
PubMed1979

Clinical profile and serum concentration of viloxazine as compared to amitriptyline.

The antidepressive effect of viloxazine (300 mg/d) was investigated during three weeks in 41 patients with depressive syndromes requiring drug-treatment against amitriptyline (150 mg/d), using a controlled double-blind design. Viloxazine differs from amitriptyline by selective inhibition of norepinephrine re-uptake, whereas amitriptyline acts also on serotonin re-uptake. Psychopathological changes were documented by means of the Hamilton Depression Rating Scale, the Bf-S (v. Zerssen), the AMDP-System, and videotaped recordings. Besides routine clinical-chemical tests, the serum concentrations of viloxazine and partly of amitriptyline were determined. Repeated EEG-recordings were evaluated by spectral analysis. The number of global responders and non-responders -- defined according to the final HDRS-scores -- was equally distributed between the two drug-groups. The AMDP-evaluation suggests that viloxazin has a somewhat more marked and more rapid effect on symptoms of retardation, whereas amitriptyline acts predominantly on depressive mood, disturbances of sleep and vital feelings. The EEG-profile of both drugs was similar to the spectral changes seen under tricyclic antidepressants, through only the viloxazine-induced changes reached statistical significance on the 10th and 20th day, the variability of the EEG-recordings being greater in the amitriptyline group. The viloxazine blood levels showed a remarkably low inter- and intraindividual variance. Steady state was reached at day 5 at the latest. Amitriptyline serum concentrations still increased between the 10th and the 21st day. The average blood concentration of viloxazine was higher in the responder- than in the non-responder-group.

Adult↗
PubMed1979

The relative toxicity of amitriptyline, imipramine, maprotiline and mianserin in rabbits in vivo.

1. Conscious or barbiturate-anaesthetized rabbits were slowly infused intravenously with solutions of amitriptyline, imipramine, maprotiline or mianserin, usually until death occurred. 2. Amitriptyline produced death at the lowest dose, imipramine and maprotiline were intermediate while much higher doses of mianserin were required. 3. Convulsions were induced by the antidepressants in all conscious rabbits and the order of potency of the drugs in producing this effect was amitriptyline greater than or equal to imipramine greater than maprotiline greater than mianserin. 4. All four drugs produced a reduction in heart rate and blood pressure in the anaesthetized rabbits and the order of potency in this respect was amitriptyline greater than imipramine greater than maprotiline greater than mianserin. 5. All four drugs produced significant changes in the ECG compared with control rabbits. The P-R interval was lengthened (potency order amitriptyline greater than imipramine greater than or equal to maprotiline greater than mianserin) and the QRS complex was widened (potency order amitriptyline greater than imipramine greater than or equal to maprotiline greater than mianserin). 7. It is concluded that all four drugs show the toxic effects classically associated with tricyclic antidepressants but the relative toxicity amongst these agents varies considerably and is in the order amitriptyline greater than imipramine greater than maprotiline greater than mianserin.

Amitriptyline↗
PubMed1978

The kinetics of amitriptyline following single oral dose administration to man.

Amitriptyline and its metabolite, nortriptyline, were measured in the plasma of eight humans for 96 hours following oral administration of a 75 mg dose of amitriptyline hydrochloride. Based on the 8 to 96 hour post dosing plasma concentration data, the terminal exponential half life of amitriptyline +/- S.D. was 22.4 +/- 4.3 hr. Based on the 24 to 96 hour concentration data, the "apparent" terminal half time of nortriptyline +/- S.D. was 26.0 +/- 7.4 hours for seven subjects. For these same seven subjects the relative area under the plasma concentration time curve of nortriptyline +/- S.D. was only 0.88 +/- 0.34 times that of amitriptyline. One subject whose apparent nortriptyline half time was 108 hours had a nortriptyline bioavailability 3.83 times that of amitriptyline. Average steady state plasma levels for 12 psychiatric patients who had received a 50 mg oral dose of amitriptyline three times a day for an average of 32 days could be predicted from the single dose plasma clearance of amitriptyline.

Adult↗
PubMed1979

Amitriptyline in migraine prophylaxis.

In a controlled trial of amitriptyline hydrochloride in migraine prophylaxis, 100 patients received placebo for a four-week baseline period and then were randomized in double-blind fashion to therapy with amitriptyline (47 subjects) or placebo (53 subjects) for another four to eight weeks. Subjects received up to four 25-mg tablets of amitriptyline hydrochloride or identical placebo per day. Comparing the first and second four-week periods for each patient, the conditions of 55.3% of amitriptyline subjects as opposed to 34.0% of placebo subjects were greater than or equal to 50% improved and the difference between amitriptyline and placebo response rates was significant (P less than .05). Nondepressed subjects with severe migraine and depressed subjects with less severe migraine responded best to amitriptyline, whereas depressed subjects with severe migraine had little headache relief. Amitritryline is an effective antimigraine agent and the antimigraine effect seems relatively independent of antidepressant activity.

Amitriptyline↗
PubMed1978

Anticholinergic and blood pressure effects of mianserin, amitriptyline and placebo.

1. Eighteen healthy male volunteers were treated at random in double-blind conditions with mianserin, amitriptyline, or placebo for 8 days. Measurements were made of various parameters indicative of anticholinergic and blood pressure effects. 2. Mianserin showed no significant anticholinergic effects on any of the measures used. Compared with placebo, mianserin significantly reduced pupil diameter and tended to increase salivary production and increase the distance of the near point. 3. Amitriptyline showed evidence of anticholinergic effects in that salivary production fell to a level significantly lower than that of the mianserin- or placebo-treated subjects. The distance of the near point tended to increase during amitriptyline treatment. Compared with placebo, amitriptyline also significantly reduced pupil diameter on some occasions. 4. Amitriptyline produced postural hypotension to a statistically significant degree, whereas this effect was not observed during mianserin treatment. 5. In conclusion, mianserin in doses of up to 60 mg daily given to healthy males seemed to lack the anticholinergic effects and postural hypotension associated with amitriptyline treatment.

Accommodation, Ocular↗
PubMed1978

The effect of amitriptyline on presynaptic mechanisms in noradrenergic nerves.

1 Electrically evoked and resting overflow of tritium was measured from mouse vas deferens previously incubated with [3H]-(--)-noradrenaline. 2 At low concentrations (1.6 X 10(-7) to 4 X 10(-6)M) amitriptyline increased only the evoked tritium overfow while higher concentrations increased both evoked and resting overflow. 3 In the presence of atropine (1 X 10(-6 M) amitriptyline still produced an increase in evoked tritium overflow. 4 In the presence of a concentration of cocaine (1.1 X 10(-5) M) which produced a maximal blockade of the uptake of exogenous noradrenaline the application of amitriptyline still produced an increase in evoked tritium overflow. 5 In the presence of a concentration of phentolamine (1 X 10(-5) M) that produced complete blockade of the presynaptic alpha-adrenoceptors, amitriptyline still produced an increase in evoked tritium overflow. 6 In the presence of cocaine and phentolamine together the effect of amitriptyline on evoked overflow was abolished. 7 It is concluded that amitriptyline may raise synaptic levels of noradrenaline by blocking presynaptic alpha-adrenoceptors controlling noradrenaline release and by blocking its uptake into sympathetic neurones.

Amitriptyline↗
PubMed1979

Adrenergic and serotonergic mechanisms in depression and their response to amitriptyline.

Our investigations into the chemical pathology of the affective disorders have indicated that depressed patients not only have significantly reduced rates of accumulation of 5-hydroxytryptamine (5-HT) into their blood platelets but their peripheral alpha-adrenoreceptors are supersensitive. Investigations into the mode of action of amitriptyline have centred on these abnormal adrenergic and serotonergic mechanisms in depressed patients. We have not detected any significant relationship between blood platelet 5-HT re-uptake inhibition and therapeutic response to amitriptyline in depressed patients, although there is a significant correlation with plasma levels of the drug. It is interesting to note that nortriptyline, the major metabolite of amitriptyline, blocks the alpha-adrenoreceptor but the degree of blocking of this supersensitive receptor is significantly correlated to poor outcome. Amitriptyline does not appear to correct these abnormal mechanisms in depressed patients. These results are discussed with reference to other pharmacological actions of amitriptyline and other antidepressant drugs.

Amitriptyline↗
PubMed1979

A placebo-controlled multicenter trial of Limbitrol versus its components (amitriptyline and chlordiazepoxide) in the symptomatic treatment of depressive illness.

In a multicenter, placebo-controlled, clinical trial, the efficacy of Limbitrol was compared with that of its components, amitriptyline and chlordiazepoxide. All patients had a diagnosis of primary depression. Data from 279 patients were evaluated using the Hamilton depression scale, the Beck depression inventory, and physician and patient global change measures. Statistically significant differences favoring Limbitrol occurred after 1 week of treatment, and a trend in favor of Limbitrol continued throughout the remaining 3 weeks. In most efficacy comparisons, the combination was as good as, or better than, amitriptyline alone. It was superior to chlordiazepoxide alone after 2 and 4 weeks of treatment. Each component produced an independent contribution to the total therapeutic effect: the chlordiazepoxide effect was more prominent in the first 2 weeks and the amitriptyline effect in the latter 2 weeks. A trend favoring amitriptyline over chlordiazepoxide was evident by week 4. The overall incidence of side effects was comparable in both Limbitrol- and amitriptyline-treated groups. Limbitrol-treated patients exhibited more sedation, but significantly fewer Limbitrol patients discontinued treatment prematurely because of side effects.

Adult↗
PubMed1978

Clinical response and plasma concentration of amitriptyline and its metabolite nortriptyline.

Plasma levels of amitriptyline and nortriptyline were measured twice weekly in 62 patients treated for three weeks with i.m. amitriptyline 120 mg/day. In half the patients the ratio of amitriptyline to nortriptyline was under 1 and in the other half it was greater than 1. 30 of these 62 patients were clinically monitored with the Hamilton Rating Scale and the side effects of the drug were recorded. There was no correlation between plasma level of the drug and its side effects, but there was a statistically significant curvilinear correlation between the plasma levels of amitriptyline plus nortriptyline and nortriptyline alone, and the clinical effect. The practical value of this type of investigation was demonstrated by showing that patients whose drug plasma level was not in the therapeutic range, were clinically improved after adjustment of the dose. The plasma level of amitriptyline plus nortriptyline must lie between 60 to 220 ng/ml, and that of nortriptyline between 60 to 140 ng/ml, to obtain the best clinical effect. Associated treatments, age, weight and sex of patients, and the type of depression did not appear significantly to affect the plasma level of the drug.

Adult↗
PubMed1978

The antiarrhythmic action of amitriptyline on arrhythmias associated with myocardial infarction in dogs.

The antiarrhythmic activity of amitriptyline, a tricyclic antidepressant, was evaluated in anesthetized dogs 24 h after coronary occlusion, during the period of spontaneous ventricular arrhythmias. In all experiments amitriptyline was administered i.v. in incremental doses of 0.3 mg/kg at 1 min intervals until a conversion to normal sinus rhythm was evident. Amitriptyline administration resulted in conversion of the ventricular arrhythmia to a normal sinus rhythm in 100% of the animals tested at a mean dose of 1.3 +/- 0.1 mg/kg. Smaller doses also resulted in a dose-related decrease in non-sinus nodal pacemaker activity. Lidocaine, when administered to the same group of animals, produced a reduction of ectopic pacemaker activity, but did not eliminate it at a cumulative dose of 2 mg/kg. Antiarrhythmic doses of amitriptyline did not produce significant changes in arterial blood pressure, cardiac output or electrocardiographic parameters associated with atrioventricular or intraventricular conduction. The results of this study suggest that at very low doses amitriptyline may be an effective antiarrhythmic agent in ventricular arrhythmias associated with myocardial ischemia.

Amitriptyline↗
PubMed1977

Mechanisms of amitriptyline induced hypothermia in the rat.

Effects of amitriptyline on rectal temperature of male rats were studied at the ambient temperature of 25 degrees C. Drugs were administered intraperitoneally. Amitryptyline elicited a dose related hypothermia. The hypothermia was attenuated by phenoxybenzamine 10 mg/kg, haloperidol 2 mg/kg, diphenhydramine 5 mg/kg, atropine 20 mg/kg, and cyproheptadine 5 mg/kg. Propranolol, at a dose of 5 mg/kg, had no effect on the hypothermia. Theophylline 50 mg/kg and dibutyryl cyclic AMP 20 mg/kg inhibited the hypothermia produced by anitriptyline. Pretreatment with parachloroamphetamine (PCA), 2 or 5 mg/kg daily for 3 days, strongly antagonized the hypothermia. In addition, pretreatment with parachlorophenylalanine (PCPA), 100 mg/kg daily for three days, reduced the brain 5-hydroxytryptamine (5-HT) concentration to 20% of the control level and completely blocked the hypothermia response. When brain 5-HT concentration recovered to 50% of the control level in PCPA treated rats following the administration of 10 mg/kg 5-hydroxytryptophan (5-HTP) the hypothermia induced by amitriptyline was restored. However, the administration of 5-HT, 5 mg/kg, to PCPA treated rats did not increase brain 5-HT concentration or restore the amitriptyline induced hypothermia (AIH). Results suggest that amitriptyline interacts with several transmitter substances to produce hypothermia. Since the ability of amitriptyline to produce hypothermia was correlated with brain 5-HT content, 5-HT might play an important role in the mediation of AIH.

Amitriptyline↗
PubMed1979

A double-blind trial with amitriptyline and lofepramine in the treatment of endogenous depression.

A double-blind trial was undertaken to compare the antidepressant efficacy and the side effects of Lofepramine with those of Amitriptyline in the treatment of endogenous depression. The study involves 22 acutely ill endogenously depressive patients. 11 patients were treated with Lofepramine and the remaining 11 with Amitriptyline. The results demonstrate that both substances are effective in the treatment of depression. However, the therapeutical efficacy of Lofepramine is significantly greater than that of Amitriptyline. Furthermore, the tolerance of Lofepramine is better than that of Amitriptyline, and the side effects of Amitriptyline, especially in blood pressure dysregulation, are greater than those of Lofepramine.

Adult↗