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Biomedical subjects

K Wood

Publications and source records attributed to K Wood.

At least 127 records · Page 7Linked to original sources
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

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

[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↗
PubMed1978

Platelet 5-hydroxytryptamine accumulation in depressive illness.

The uptake of 5-hydroxytryptamine (5-HT) by blood platelets from controls, depressed patients and recovered depressed patients has been determined using short incubation times and low substrate concentrations. The affinity of serotonin for the platelet membrane appears to be normal in acutely depressed and recovered depressed patients. The capacity of transport of 5-HT through the platelet membrane is impaired in these depressive patients and this impairment is independent of the psychiatric status of the patients and is discussed in the light of the electrolyte and enzyme disturbances that are associated with depressive illness.

Biological Transport, Active↗
PubMed1978

Tryptophan and depressive illness.

Plasma free tryptophan is significantly decreased in monopolar, depressed patients. No evidence was found to suggest that poor nutritional history prior to hospital admission was responsible for these low levels. Factors known to influence tryptophan-albumin binding in plasma, e.g. concentration of plasma proteins, albumin and non-esterified fatty acids, did not account for the low levels of free tryptophan in depressed patients. A significant decrease in plasma free tryptophan levels was found in perimenopausal but not in pre- or post-menopausal female controls. This mirrors the decrease in circulating oestrogens. Although exogenously administered oestrogens do not have any therapeutic efficacy in relieving mild residual depressive symptoms of lithium treated patients, they increased the levels of plasma free tryptophan. Clofibrate also displaces tryptophan from plasma protein binding sites in both depressed patients and controls. Utilization of the increased levels of plasma free tryptophan is reduced in depressed patients. A situation therefore exists in depressed patients where the plasma free tryptophan is not only reduced but also leaves the plasma less readily than in control subjects.

Blood Proteins↗
PubMed1978

Effect of mianserin hydrochloride on peripheral uptake mechanisms for noradrenaline and 5-hydroxytryptamine in man.

1. Mianserin seems to have little effect on peripheral noradrenaline (NA) re-uptake mechanisms as shown by its lack of effects on the tyramine dose and NA dose/pressor response. 2. Mianserin has no effect on the hypotensive action of bethanidine. 3. Mianserin in vivo has a significant action on platlet transport (Vmax) of 5-hydroxytryptamine (5-HT), which changes toward normal values in depressive patients on the drug. This action is not observed in vitro. 4. It is possible that a metabolite of mianserin is responsible for this effect, and that this may be of therapeutic importance.

Antidepressive Agents↗
PubMed1977

Red cell adenylate kinase phenotypes in the affective disorders.

The red cell adenylate kinase (AK) phenotype was determined by starch gel electrophoresis in 96 adult Caucasian subjects with affective disorders (24 with bipolar illness and 72 with unipolar illness). The phenotype frequencies and the gene frequencies of the bipolar group closely resembled that of the control subjects (180 subjects drawn from the population of a large institution for the mentally retarded), the unipolar group however, showed a significant increase in the frequency of the AK2 allele. The significance of these results have been discussed in relation to the known genetic and biochemical findings in the affective disorders. It is suggested that the mechanism involved may be a reduction of the enzyme activity in the tissues of subjects with the AK 2:1 phenotype. This may present a selective disadvantage in the form of a decrease in control of energy metabolism in general, and control of adenine nucleotide levels in nervous tissue in particular.

Adenylate Kinase↗