Catabolism of adenosine 5'-monophosphate in promastigotes of Leishmania tropica.
Lamotrigine, amitriptyline, mexiletine, and carbamazepine decreased peak micturition pressure, micturition interval, and void volume. These effects were markedly similar to observations with muscarinic antagonists. Therefore, we evaluated the selectivity of these agents against bladder muscarinic receptors. Lamotrigine, mexiletine, and carbamazepine had no effect on muscarinic bladder contractions, whereas amitriptyline displayed a robust antagonism of carbachol-induced contractility.
Using data from a therapeutic drug monitoring database, kinetic interactions between the neuroleptics zuclopenthixol and perphenazine and tricyclic antidepressives were studied. Out of 290 patients monitored for amitriptyline and 611 patients monitored for nortriptyline, 77 patients were comedicated with perphenazine and 50 patients with zuclopenthixol. Comedication with perphenazine increased the median steady-state serum concentration to daily dose ratio (C/D) of nortriptyline by 30-45%, whereas the median C/D of amitriptyline was unaffected. On the contrary, median C/D values of nortriptyline and amitriptyline were not significantly influenced by comedication with zuclopenthixol. Thus, in accordance with previous studies, perphenazine increases the concentration of tricyclic antidepressives to a moderate extent. Zuclopenthixol, on the other hand, does not exert any impact under routine therapeutic drug monitoring, even though the drug is known to partly depend on metabolism by the isozyme cytochrome P450 2D6.
After placing rats or mice into the cylinders filled with water the animals after initial period active swimming, take the immobilization position the time of which is minimized by administering antidepressants. Experiments were made with random-bred, tetrahybrids CBWA, and C57BL/6, BALB/c, CBA, F1 CBA/c55BL mice. Tetrahybrids CBWA appeared to be an optimal species for making experiments. The use of the "swimming test" made it possible to identify the activity of tricyclic (desipramine, chlorimipramine, amitryptyline) and atypical antidepressants (befuralin, zimelidine, trazodon), that of pyrazidol (type A MAO inhibitor) and of a number of new compounds--derivatives of benzofuran and morpholine upon single and chronic administration. To define the method specificity, use was made of the neuroleptic haloperidol, the tranquilizer diazepam, and of nembutal, which did not exhibit any activity in the test in question. Psychostimulants (amphetamine, caffeine) dramatically increased the time of active swimming. The effect lasted throughout all the 30 minutes of testing, which is not characteristic for antidepressants.
The National Institute of Mental Health (NIMH) Treatment of Depression Collaborative Research Program (Elkin et al., Archives of General Psychiatry, 46, 971-982; 1989) reported treatment-by-severity interactions favouring pharmacotherapy for more depressed outpatients, on a minority of relevant comparisons. The present study reports secondary analyses from a similar, preexisting data set in which treatment-by-severity interactions are systematically investigated with depressed outpatients treated either with nondirective psychotherapy, behaviour therapy, pharmacotherapy, or relaxation/placebo. Despite multiple severity measures and variable severity cut scores, no treatment was differentially effective in improving more severely depressed patients. Also, there was little difference across symptom severity levels in the proportions of recovered patients between treatment groups. Finally, dynamic cluster analysis demonstrated that the proportion of pharmacotherapy nonresponders (20%) did not differ from the proportion of nonresponders in behaviour therapy or placebo groups. It is concluded that this failure to replicate the NIMH trial findings can not be attributed to treatment differences, populations or statistical power. The suggestion that pharmacotherapy be the treatment of choice for more severely depressed outpatients appears to be unjustified on the basis of available evidence.
Double-blind techniques were used. The subjects were given the medications two hours before they were rotated in a chair making head movements until a symptom total short of vomiting was reached. Standardized N.A.S.A. techniques were used for speed of rotation and end-point of motion sickness.
Antidepressant activity of Proproten-100 (antibodies to brain-specific S100 protein in ultralow doses) in patients with stage II alcohol dependence and alcohol withdrawal syndrome was studied in an open comparative clinical trial. The tricyclic antidepressant amitriptyline and benzodiazepine tranquilizer phenazepam served as reference preparations. Anxiolytic activity of Proproten-100 was highly competitive with that of phenazepam. Proproten-100 produced a stronger thymoleptic effect than amitriptyline. The preparation possessed activating properties, affected alcohol addiction, and did not cause side effects. Proproten-100 should undergo clinical tests during the therapy of neurotic, neurosis-like, and subdepressive borderline disorders.