[Contribution to the effect of tri and tetracyclic antidepressive agents on heart and circulation].
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Biomedical subjects
Publications and source records attributed to M Peet.
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Initial velocity patterns for human placental choline acetyltransferase show a series of converging lines for both the forward and reverse reaction; with Kacetyl coenzyme A = 11.9 micron, Kcholine = 0.41 mM, KCOA = 8.8 micron, and Kacetylcholine = 1.3 mM. The relative rates of acetylcholine synthesis (Vf) to acetylcholine breakdown (Vr) is 4.5. Product inhibition by acetylcholine is competitive with respect to choline and noncompetitive with respect to acetyl-CoA, while product inhibition by choline is competitive with respect to acetylcholine and noncompetitive with respect to coenzyme A. Chlorocholine, diethylaminoethanol, and acetylaminocholine were used as dead-end inhibitors and shown to inhibit competitively with respect to acetylcholine, and noncompetitively with respect to choline, acetyl-CoA, and CoA. At high choline concentrations, uncompetitive substrate inhibition is observed, and inhibition by acetylaminocholine changes from noncompetitive to competitive. Comparing the reactivity of dimethylaminoethanol to choline, and acetyldimethylaminoethanol to acetylcholine, the maximal velocities obtained with these analogues was approximately 25% of the natural substrates. These data are not consistent with the previously proposed ordered Theorell-Chance reaction mechanism, and have been interpreted in terms of a random binding mechanism.
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In the course of a double-blind comparative trial of mianserin versus amitriptyline in the treatment of depressive illness, E.C.G. was recorded before and after three weeks of treatment in 27 female patients. Mianserin had no consistent effect on heart rate, PR interval, QRS width, or T wave amplitude. This is consistent with other data suggesting that mianserin lacks cardiotoxic effects. In contrast, amitriptyline treatment was associated with increases in heart rate and PR interval, and these effects were statistically significant in comparison to the mianserin group. This finding is consistent with the known cardiotoxicity of amitriptyline.
Mianserin in a dosage of 20 mg 3 times daily, was given to 13 patients with bipolar affective illness, who were previously maintained on lithium. 3 patients left the trial at their own request within a few days due to drowsiness in 2 cases and insomnia in the third. Of the remaining 10 patients, 6 became manic within the 3-month trial period. This result indicates that mianserin may be capable of precipitating mania in susceptible subjects with bipolar affective illness. This may be a general property of antidepressants, since it has been previously described with other groups of antidepressants.
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Erythrocyte sodium and potassium concentrations, erythrocyte membrane ATPase (Na-K specific and non-specific) and the rate of potassium influx into erythrocytes (ouabain-sensitive and insensitive) were estimated in a group of female patients suffering from mania and repeated on about two thirds of them when they had recovered. With recovery there was a statistically significant increase in the erythrocyte ouabain-sensitive potassium influx. The other parameters showed no significant overall change with recovery but the initial severity correlated significantly and negatively with the change in erythrocyte Na-K ATPase with recovery. The changes that occurred in the erythorcyte sodium concentration and Na-K ATPase activity were not random since they correlated significantly with changes in the active potassium influx.
Total and free plasma trytophan levels were measured in depressive and manic patients before and after recovery. No change was found in total or free plasma trytophan concentration on recovery from depressive illness. Free plasma tryptophan levels were higher in recovered manics than in active manics, and a group of four manic patients tested before and after recovery showed a significant increase in free plasma tryptophan concentration on recovery.
Whole blood cell ATP concentration was estimated in a group of manic and depressed patients and in a group of normal subjects. There were no significant differences between patient and control groups, nor in the patient groups were there any significant changes with recovery.
Plasma levels of total and free tryptophan were measured in patients with depressive neurosis and depressive psychosis, before and after recovery. No significant differences were found in total or free plasma tryptophan levels between 'neurotic' and 'psychotic' groups, and no change in these levels was found on recovery from depressive illness.
A suggestion that mania is associated with an increased membrane transport of sodium has been investigated in a double-blind trial of a specific Na-K A.T.P.ase inhibitor (digoxin) in twelve female inpatients with mania. Digoxin had no effect.
The potential difference across the rectal mucosa (rectal p.d.) is generated by the active transport of sodium across the mucosa, and it is sensitive to the action of aldosterone. The rectal p.d. values of depressive patients on no treatment, tested whilst depressed or after recovery, were found to be similar to those of control subjects, indicating that sodium transport across the rectal mucosa and the activity of aldosterone were normal in these patients. This contrasts with previous reports of abnormalities of sodium transport and of aldosterone levels in manic-depressive patients. Manic-depressive patients taking lithium carbonate as a prophylactic agent were found to have significantly elevated rectal p.d. values when normothymic. Patients who had become depressed whilst taking lithium, and in whom prophylaxis had therefore failed, were found to have normal rectal p.d. values. Lack of elevation of rectal p.d. in response to lithium administration may be a characteristic of patients who fail to respond to lithium prophylaxis.
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