PubMed Health⌕ Search

Biomedical subjects

A Coppen

Publications and source records attributed to A Coppen.

At least 19 recordsLinked to original sources
PubMed1979

Urinary 4-hydroxy-3-methoxyphenylglycol is not a predictor for clinical response to amitriptyline in depressive illness.

The urinary excretion of 4-hydroxy-3-methoxyphenylglycol was compared in a group of 23 depressive patients and 27 control subjects of similar age. There was no difference between patients and controls although female controls excreted less than males. After 6 weeks' treatment with 150 mg daily of amitriptyline there was no correlation between therapeutic response and pretreatment urinary excretion value.

Amitriptyline↗
PubMed1979

Zimelidine: a therapeutic and pharmacokinetic study in depression.

Zimelidine, a bicyclic compound with a strong effect on the neuronal reuptake of 5-hydroxy-tryptamine and with weak anticholinergic actions, was evaluated for its antidepressant efficacy in a double-blind comparative trial with amitriptyline. In doses of 200 mg a day it was found to be as effective as 150 mg amitriptyline, but with significantly less subjective side-effects. The plasma concentration of zimelidine and its metabolite, norzimelidine, showed no significant correlation with therapeutic outcome.

Allylamine↗
PubMed1979

Inhibition of 5-hydroxytryptamine reuptake by amitryptyline an zimelidine and its relationship to their therapeutic action.

Amitriptyline and zimelidine significantly reduce the uptake of 5-HT into the blood platelets of depressive patients. The degree of inhibition is significantly correlated with the plasma drug level of amitriptyline. No significant relationship could be detected between the degree of inhibition of uptake and therapeutic outcome. The accepted mode of action of tricyclic antidepressant drugs and the deficiency hypotheses of affective disorders are discussed.

Allylamine↗
PubMed1979

Decreased cerebrospinal fluid concentration of free phenylacetic acid in depressive illness.

Cerebrospinal fluid free phenylacetic acid concentration in a series of depressive patients was significantly lower than values in control subjects. This acid derives from phenylethylamine and the findings may reflect a decrease in its brain formation. Such a deficit may be related to other recent observations of a decrease in urinary output of the major metabolites of the "trace amines", octopamine and tyramine: phenylethylamine is thought to be the precursor of these "trace amines".

Adult↗
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

Tryptophan accumulation by blood platelets of depressed patients.

The accumulation of tryptophan by blood platelets has been investigated in depressive patients and controls using short incubation times and low substrate concentrations. The accumulation of tryptophan by the platelet is significantly greater in the acutely depressed patients than the control group. The results are discussed with reference to tryptophan transport in depression and also to the regulation of plasma levels of tryptophan.

Biological Transport, Active↗
PubMed1979

Pharmacokinetics and pharmacodynamics of amitriptyline in depression.

1. The therapeutic effect and pharmacokinetics of amitriptyline were assessed in thirty-five patients suffering from primary depressive illness during inpatient treatment. 2. Contrary to our previous study, no significant correlation was obtained between the plasma concentrations of amitriptyline, nortriptyline or total tricyclics with Hamilton rating score at 6 weeks or percentage improvement after 6 weeks treatment. 3. There was also no correlation with the plasma concentrations of tricyclics with the corrected subjective side-effects score. 4. A linear correlation (rs = 0.80; p less than 0.001) was observed between the plasma concentration of nortriptyline and decreased tyramine sensitivity, an index of noradrenaline reuptake blocking effect. 5. The corrected side-effect score during the trial correlated (r = 0.64; p less than 0.001) with Hamilton rating score at week 6, i.e. the patients who complained of more side-effects had less clinical benefit during amitriptyline therapy.

Amitriptyline↗
PubMed1979

Classification of depression and response to amitriptyline therapy.

Fifty-four patients suffering from primary depressive illness were rated on the Newcastle diagnostic scale while taking part in a pharmacokinetic study of amitriptyline therapy, and their clinical response was assessed by the Hamilton Rating Scale for depression. Patients with a Newcastle score of 4-8 showed the best response to amitriptyline. Patients with low Newcastle scores, representing the non-endogenous or neurotic group, responded poorly. Patients with high scores on the Newcastle scale, representing those with marked endogenous features, also responded poorly.

Amitriptyline↗
PubMed1979

[Indoleamine precursors in depression (author's transl)].

Tryptophan and 5-hydroxytryptophan have now been extensively investigated in affective disorders. There is now very good evidence that tryptophan increases the antidepressant activity of monoamine oxidase inhibitors. The antidepressant activity of tryptophan and 5-hydroxytryptophan has also been the subject of numerous investigations. There is evidence that patients with decreased cerebrospinal fluid concentration of 5-hydroxyindoleacetic acid respond particularly favourably to this treatment. The therapeutic activity of tryptophan has led to the investigation of the plasma concentration of tryptophan. Free plasma tryptophan, that is tryptophan unbound to plasma protein, appears decreased. There is also evidence that tryptophan and 5-HT transported are abnormal in depression.

Depression↗
PubMed1978

The effect of antidepressant drugs on plasma kynurenine in depressed patients.

The concentration of kynurenine in plasma from depressed patients and control subjects has been measured using a sensitive and specific method. The levels of kynurenine in the plasma of depressed patients and controls are not significantly different and are not influenced by age or sex. The severity of affective disturbance was not related to plasma kynurenine levels in depressed patients. Clinical outcome could not be accurately predicted by measurement of plasma kynurenine levels. Amitriptyline did not significantly increase plasma kynurenine concentration in vivo, whereas lithium and mianserin did have a significant effect. These results are discussed with reference to known abnormalities of tryptophan metabolism in depressive illness and in particular to the 5-hydroxytryptamine uptake characteristics of blood platelets in depressive patients.

Amitriptyline↗
PubMed1978

Decreased tryptophan excretion by depressive patients.

The concentration and 24-h urinary excretion of tryptophan has been measured in urine samples from monopolar female depressed patients and female control subjects. Female depressed patients and the control subjects excrete similar amounts of tryptophan. Patients with endogenous features of depression excrete significantly less tryptophan in 24 h than do the patients with reactive features and the control subjects. The relationship between plasma tryptophan concentration and 24-h urine tryptophan excretion in control subjects has been investigated and the results discussed in the light of abnormalities of tryptophan metabolism in depressive illness.

Antidepressive Agents, Tricyclic↗