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Ethanol effects on brain concentrations of amitriptyline and the relationship to psychomotor function.

The effect of amitriptyline (AMI), ethanol (ETOH), and ETOH followed by AMI on both general activity (open field) and motor performance (two rotorod tasks) was tested in reference to a saline-injected control. The combination (ETOH plus AMI) produced greater impairment on all three tasks than did either drug alone. ETOH pretreatment also produced a 223% increase in the total tricyclic antidepressant (TCA) brain concentration. The decrement in motor performance was logarithmically related to total TCA brain concentrations in both animals treated with AMI alone and those pretreated with ETOH prior to AMI. The concentration which consistently produced behavioral impairment was similar to those previously reported to cause cognitive and electroencephalographic dysfunction in humans.

Amitriptyline↗

Citalopram, a selective serotonin reuptake inhibitor: clinical antidepressive and long-term effect--a phase II study.

In a phase II study the antidepressive effect of citalopram, a selective and potent serotonin reuptake inhibitor, was examined in 20 endogenously and three non-endogenously depressed hospitalized patients. Four endogenously depressed patients dropped out due to deterioration early in the treatment period. The remaining 19 patients completed a 4-6 week treatment schedule. Of 16 endogenously depressed patients 11 responded, one was a partial responder and four did not respond. Of three patients with non-endogenous depressions, two responded and one did not respond. No correlation between plasma citalopram concentration and therapeutic outcome was found. Fourteen patients were given maintenance treatment for 8-113 weeks. One patient developed depression when the dose was reduced from 60 to 40 mg and one patient became manic. After discontinuation of treatment seven patients had a depressive relapse and six of these who again were treated with citalopram responded completely. Side effect rating scores of symptoms usually associated with depression or treatment with tricyclic antidepressants declined during treatment. Three patients complained of increased need of sleep for a period after several weeks of treatment. Apart from an unspecific, transient rise in liver enzymes in two patients, detailed biochemical laboratory tests were all normal. There were no effects on blood pressure, pulse rate, orthostatic reaction, or electrocardiogram. One patient took an overdose of citalopram resulting in plasma levels about six times higher than the average therapeutic level, but there were no signs of severe toxicity. In particular no change in consciousness, electrocardiogram or blood pressure occurred. Pharmacokinetic variables such as dose schedule, steady state kinetics, and metabolism are discussed.

Adult↗

Effects of combined treatment with nortriptiline and lorazepam on conflict behavior and motility of rats.

Lorazepam attenuated the suppressant effects of punishment on the response rate of rats in the multiple schedule of reinforcement devised by Geller and Seifter (1960). Nortriptiline alone was ineffective on punished responses. Both drugs, at certain dose levels, inhibited the nonpunished response. Combined treatment with the two drugs in a dose ratio of 1:20 attenuated the effects of punishment at all dose levels tested. The effects of the combination upon both punished and nonpunished responding was greater than might be accounted for by a simple additive effect of the individual treatments. Lorazepam and nortriptiline both induced a dose-related decrease in the locomotor activity of rats; when given together the 2 drugs antagonized each other. The results give an experimental support to the clinical observations about the usefulness of the benzodiazepine-antidepressant combination in certain depressive illnesses.

Animals↗

Measurement of plasma levels of tricylic psychoactive drugs and their metabolites by UV reflectance photometry of thin layer chromatograms.

A method has been developed for the determination of perazine, clozapine, imipramine and amitriptyline and their demethylated metabolites in plasma. Other metabolites measured were perazine sulfoxide and the N-oxides of clozapine and perazine, the latter two following their reduction to the parent drugs with ascorbic acid. 10-Hydroxynortriptyline was identified as an amitriptyline metabolite in plasma. The general procedure included extraction of alkalinized plasma samples (3 - 6 g) with benzene or toluene and thin layer chromatography of the extracts, followed by reflectance photometry of the plates at appropriate wave lengths in ultraviolet light. Spots of questionable identity were further characterized by two-dimensional chromatography and by colour reactions. Therecoveries of compounds added in therapeutic concentrations were between 70 and 98 %. The limits of detectability were 5 - 10 ng/g plasma.

Amitriptyline↗

Effects of chronic antidepressant treatment on alpha 1- and alpha 2-adrenoceptors in the rat anococcygeus muscle.

The effects of a single administration (48 hours) and of chronic (14 days) treatment with tricyclic (desipramine, nortryptiline) and nontricyclic (mianserin, nomifensine) antidepressant drugs on responses of the isolated anococcygeus muscle to the alpha 2-adrenoceptor agonist xylazine (inhibition of contraction to field stimulation at 1 Hz) and to the alpha 1-adrenoceptor agonist phenylephrine (contraction of the muscle) have been studied. Of the drugs used only desipramine and nortryptiline administered chronically reduced the responsiveness of the anococcygeus muscle to phenylephrine suggesting a desensitization of postsynaptic alpha 1-adrenoceptors. Long-term but not acute administration of antidepressants resulted in significant decrease in sensitivity of presynaptic alpha 2-adrenoceptors to xylazine. These results show that the adaptative changes of alpha-adrenoceptors in the rat anococcygeus muscle following long-term administration may depend on the efficiency to inhibit the neuronal uptake and the ability to antagonize alpha 1-adrenoceptors.

Animals↗

Role of oxidation polymorphism on blood and urine concentrations of amitriptyline and its metabolites in man.

We have measured the metabolites (demethylated and hydroxylated) of amitriptyline in a group of seven normal volunteers. They were phenotyped as extensive or poor metabolizers using debrisoquine and bufuralol. The results demonstrate that the oxidative metabolism (aliphatic hydroxylation) of amitriptyline is under the same genetic control as that of debrisoquine and bufuralol. However, phenotypic polymorphism cannot be used to predict amitriptyline blood concentration after a single oral dose, since the principal metabolic pathway of amitriptyline is demethylation and not aliphatic hydroxylation.

Adult↗

[COPD-rehabilitation].

Rehabilitation of COPD-patients is an important part of the therapeutic management. The effects of endurance- and resistance-training as well as respiratory muscle-training are evident. Smoking cessation therapy is standardized, effective and cheap, and is the prerequisite of a successful COPD management. Patients with severe or very severe COPD not only have to inhale their medication exactly, but also have to undertake physical exercise and optimize their body weight. This cannot normally be achieved without adequate education. A structured patients' education optimizes all therapeutic action and is an integral part of the management of COPD.

Acupuncture Therapy↗