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Biomedical subjects

R Amrein

Publications and source records attributed to R Amrein.

At least 37 records · Page 2Linked to original sources
PubMed1994

Monoamine oxidase inhibitors, cognitive functions and neurodegenerative diseases.

Recent data obtained in animals and in humans suggest that both MAO-A and MAO-B inhibitors present cognitive enhancing properties of possible interest in the treatment of cognitive disorders. In addition, the rational for using selegiline as a neuroprotector in Parkinson's disease may also be applicable in Alzheimer's disease in which a dramatic increase in the MAO-B activity has been reported. It seems then worthwhile to investigate the neuroprotective effect of MAOIs in humans and to assess, furthermore, the real therapeutical benefit of their cognitive enhancing properties.

Alzheimer Disease↗
PubMed1994

Safety and efficacy during long-term treatment with moclobemide.

Safety aspects [adverse events, blood pressure and heart rate, weight, and laboratory tests (liver parameters, hemoglobin, leukocytes)] of long-term treatment in 1,120 patients are discussed. Adverse events during this long-term treatment were also compared with those of a subgroup of these patients who, before long-term treatment, were treated on a short-term basis (n = 706). Efficacy [Hamilton Depression Rating Scale (HAM-D), Clinical Global Impression of Efficacy (CGI), and occurrence of relapses and recurrences] in a homogeneous sample of 485 patients is also discussed. The adverse events most frequently observed during long-term treatment were insomnia, headache, and dizziness. Insomnia and headache were also most often occurring in the compared sample of patients with short-term treatment, whereas dizziness during this treatment period ranked at the fifth position. Supine and standing mean blood pressure did not consistently change during long-term treatment, the most prominent increases in comparison with baseline were seen in the period > 1 year of treatment (6.3 mm Hg supine/7.2 mm Hg standing). Comparison of blood pressure values in the hypertensive range at baseline and during long-term treatment revealed no statistical difference (McNemar test p = 0.07829). Mean heart rate slightly decreased during long-term treatment (by a maximum of 6.3 beats/min supine, 8.2 beats/min standing). Mean weight did not change between baseline and treatment end point. There were 23 patients with a weight loss of 10 kg or more and 16 patients with a weight gain of 10 kg or more. For none of the laboratory parameters tested was there a statistical significance regarding shifts from normal to pathological values. HAM-D mean total scores in the above-mentioned subgroup of patients decreased from 25.05 points at baseline (n = 485) to 7.88 points after 1 year of treatment (n = 139). Seventy-five patients who had favorably responded to treatment (total responders n = 300) relapsed during the first 6 months of treatment. During the second half-year of treatment the recurrence rate was 14.8%, and during the third 6 months the recurrence rate was 12.2%. CGI in the same subsample of patients in whom HAMD was evaluated (n = 485) compared with those patients who did not drop out during the short-term period up to 44 days and entered long-term treatment (n = 401) showed that the percentage of the ratings "no change/worse" was higher in the sample that also included patients who withdrew from treatment during the short-term period.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

RIMA--a new concept in the treatment of depression with moclobemide.

Moclobemide, a specific reversible inhibitor of monoamine oxidase that shows a preference for the A isoenzyme, has been developed as a new antidepressive agent. Unlike earlier generation monoamine oxidase inhibitors, moclobemide is devoid of any clinically significant tyramine interaction, thus making dietary restrictions during therapy unnecessary. In comparative trials, moclobemide has been found to be superior to placebo and similar to imipramine, clomipramine, and amitriptyline in clinical efficacy. Long-term trials involving moclobemide therapy for up to one year have indicated that antidepressant efficacy can be maintained for this period. Tolerance is good and is significantly better than for tricyclic antidepressants. In addition, unlike the tricyclic antidepressants, overdoses of moclobemide do not appear to be life-threatening.

Benzamides↗
PubMed1992

Interactions of moclobemide with concomitantly administered medication: evidence from pharmacological and clinical studies.

Interactions may occur on pharmacological or pharmacokinetic grounds. Both types of interactions are discussed in relationship with the pharmacological and pharmacokinetic data of moclobemide, a reversible MAO-inhibitor. A variety of interaction studies either designed more specifically as kinetic or as dynamic studies have been performed with moclobemide. The results of these studies are presented. In view of these results as well as in view of data stemming from clinical trials it can be concluded that apart from interactions with cimetidine and pethidine, moclobemide has been shown to be devoid of relevant interactions.

Animals↗
PubMed1992

Long-term treatment with moclobemide. An open-label, non-comparative, multiple-distributed study in patients with a major depressive episode as defined by DSM-III.

Evaluation of 247 patients receiving long-term moclobemide treatment showed that it was effective as an antidepressant, as measured both by decrease in HAMD mean total score and the doctor's evaluation of therapeutic effect. In patients who had been treated for 6 months or less, results were less favourable (ratings of 'very good' or 'good' in 31.5%, compared with 81.3% in patients treated for more than 6 months). This was due to a higher number of drop-outs, as a result of insufficient efficacy in the first 6 months. In those patients who responded favourably, 9.2% relapsed within 6 months of commencing treatment; of the remaining responders, 16% relapsed during months 7-12. In terms of the doctor's evaluation of side-effects, tolerability was 'very good' or 'good' in 88.2%.

Antidepressive Agents↗
PubMed1992

Pharmacotherapy of social phobia. A controlled study with moclobemide and phenelzine.

In a double-blind, parallel group trial, 78 subjects with social phobia received moclobemide (a new reversible inhibitor of monoamine oxidase A) phenelzine, or placebo. After eight weeks, both active drugs-phenelzine somewhat more than moclobemide--were clinically and statistically significantly more effective than placebo, as assessed by rating scales. There was some further improvement between weeks 8 and 16, particularly in the moclobemide group; at week 16, 82% of the moclobemide and 91% of the phenelzine-treated patients were almost asymptomatic. Moclobemide was, however, much better tolerated than phenelzine. Patients withdrawn from active drugs had relapsed by week 24, providing additional support for the efficacy of the active drugs.

Adult↗
PubMed1992

RIMA: a safe concept in the treatment of depression with moclobemide.

Moclobemide--a new, safer antidepressant drug--is described and clinical studies are reviewed. Moclobemide represents a new class of drug, the so-called RIMA compounds--reversible inhibitors of MAO-A. Unlike classical monoamine oxidase (MAO) inhibitors, moclobemide is devoid of hepatotoxicity and has only a slight potentiating effect on the hypertensive action of tyramine; treatment does not require a tyramine-restricted diet. Studies comparing moclobemide with tricyclic antidepressants (TCAs) indicate that moclobemide is significantly better tolerated than TCAs and slightly less well tolerated than placebo.

Antidepressive Agents, Tricyclic↗
PubMed1990

Pharmacology of Dormicum (midazolam) and Anexate (flumazenil).

Midazolam and flumazenil have some characteristics in common which make them suitable partners as benzodiazepine (BZD) agonist and antagonist. After intravenous (i.v.) administration, both drugs are rapidly distributed into similar distribution volumes, from which they are cleared with a comparable short elimination half-life (t1/2 beta) in the range of 1 h (flumazenil) to 3 h (midazolam). Both drugs undergo hepatic metabolisation with a relatively high hepatic extraction ratio of around 0.3 for midazolam and 0.6 for flumazenil. The metabolisation of midazolam and flumazenil may equally be affected by considerable loss of active liver cells or by temporarily reduced hepatic blood flow. In such a case, elimination of both drugs may be prolonged in the same way. Flumazenil has only an inactive metabolite. The main active alpha-hydroxy-metabolite of midazolam does not contribute much to the activity of midazolam after parenteral administration. Its potency is lower than that of midazolam and its shorter elimination half-life (0.8 h) does not prolong the activity of the parent drug. As indicated by the therapeutic index, both drugs have a very high safety margin, which is considerably higher than that of thiopentone or propofol. Only low doses of both drugs are necessary to produce initial effects. Increasing doses intensify the drug activity and a ceiling effect is observed after maximal doses of midazolam and flumazenil. The onset of effect immediately follows the diffusion of the substances into the CNS and can be observed within the first minutes following flumazenil or midazolam administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Review of comparative clinical trials. Moclobemide vs tricyclic antidepressants and vs placebo in depressive states.

Moclobemide is a reversible monoamine oxidase inhibitor (MAOI) which preferentially inhibits type-A MAO. In the present communication the results obtained with moclobemide in various clinical trials are reviewed. To this day, the antidepressant efficacy of moclobemide has been compared to that of placebo in four trials. The antidepressant efficacy of moclobemide (300-600 mg/d; N = 164) was found to be superior to that of placebo (N = 162) and comparable to that of imipramine (100-200 mg/d; N = 164) in a 6-w., double-blind, multicentre study, in patients suffering from a Major Depressive Episode (DSM-III). Two smaller trials, strongly suggest that moclobemide is more efficacious than placebo for the treatment of endogenous depression (ICD-9) and for the treatment of Dysthymic Disorders (DSM-III). The antidepressant efficacy of moclobemide was compared to that of imipramine, desipramine, clomipramine and amitriptyline. The antidepressant efficacy of moclobemide (300-600 mg/d; N = 189) was found to be comparable to that of imipramine (100-200 mg/d; N = 192) in a 4-w., double-blind, multicentre study, in patients suffering from a Major Depressive Episode. This finding is supported by the results obtained in 12 other smaller studies, using either imipramine, desipramine, clomipramine or amitriptyline as comparator drug. When the tolerability of moclobemide, as judged by reported and observed adverse events, is compared to that of placebo, it appears that only nausea is reported significantly more frequently with moclobemide than with placebo (9.5% vs 4.8%). In the trials comparing moclobemide to tricyclic antidepressant drugs (TCAs), the tolerability of moclobemide was constantly found to be superior to that of the TCAs; in particular the incidence of anticholinergic side effects was low with moclobemide and was significantly higher with the TCAs. The cardiovascular tolerability of moclobemide tended to be superior to that of the TCAs. Physical examination, hematology and clinical chemistry did not seem to be affected by treatment in any of the studies summarized in this review.

Antidepressive Agents, Tricyclic↗
PubMed1989

The pharmacology of reversible monoamine oxidase inhibitors.

The older monoamine oxidase inhibitors (MAOIs) are mechanism-based, irreversible inhibitors of MAO; most inhibit both the A and B forms of MAO. Several of the drugs are hydrazine derivatives which have non-specific effects other than MAO inhibition. These properties convey disadvantages, which may be seen as serious, though infrequent, adverse events--the 'cheese effect', hepatotoxicity, amphetamine-like activity, orthostatic hypotension and anticholinergic effects. New, reversible MAOIs stem from a variety of chemical classes and are more specific in their effects, with relatively rapid onset of action, direct relationship between plasma concentration and pharmacological effect, and no prolonged carry-over phenomena.

Administration, Oral↗
PubMed1988

Clinical pharmacology of flumazenil.

(1) Flumazenil is a highly specific benzodiazepine (BZ) antagonist. It exerts its effect by competitive interaction at the BZ receptor site. (ii) Flumazenil antagonizes all central BZ effects irrespective of its contiguity to the BZ administration. (iii) The pharmacological effect of flumazenil depends upon the number of BZ receptors that can be occupied by flumazenil according to the mass-action law. Receptor occupancy is determined by the affinity of the BZ for the receptor and the free BZ concentration near the receptor. (iv) The minimal effective dose of flumazenil is 0.2 mg. After extreme BZ overdose 1 mg may be needed. (v) The optimal dosing strategy starts with an initial dose of flumazenil 0.2 mg i.v. The administration of further low doses of 0.1 mg at 1-min intervals allows the interruption of the injection of flumazenil exactly at the stage of vigilance that is most convenient for the patient. (vi) The duration of effect depends upon the type and dose of the administered BZ, the dose of flumazenil, and the time interval between flumazenil and the BZ administration. (vii) The therapeutic or safety index is above 3000, which means that a 3000 times overdose is still tolerated.

Animals↗
PubMed1988

Antidepressant drug therapy: associated risks.

Aspects of risks associated with treatment with three classes of antidepressants: tricyclic (TCA), second generation ("new") antidepressants and monoamine oxidase inhibitor (MAOI), are discussed. Moclobemide, a benzamide derivative, is a new MAOI antidepressant with reversible and preferential inhibition of the A-form of monoamine oxidase. Moclobemide is free of liver toxicity and the risk of a pressor response with tyramine-containing food is so low that strict diet restrictions are unnecessary. That MAOIs have a low incidence of side effects, particularly so called anticholinergic side effects is also true for moclobemide. A serious risk with antidepressant drugs is that the patient will use them to attempt suicide. Therefore important aspects of antidepressants are that they should take effect rapidly and be safe in overdose. No deaths from overdose have been observed with toloxatone, the only reversible MAOI antidepressant on the market to date. It is concluded that the new reversible MAOI antidepressant moclobemide is similar to other antidepressants in terms of efficacy but very noticeably superior in terms of tolerance and safety.

Aged↗
PubMed1988

Interaction of moclobemide, a new reversible monoamine oxidase inhibitor with oral tyramine.

In a double-blind placebo-controlled cross-over study in 8 healthy volunteers possible interactions between moclobemide and tyramine were studied. Eight volunteers received either moclobemide or placebo for a period of 6 days and received tyramine on day 5 and day 6 of each treatment period. Moclobemide was given in a daily dose of 450 mg to be taken in three divided doses at the end of the meals. Tyramine was administered in the form of an artificially tyramine enriched cheese (camembert) together with a meal at noon. The total tyramine doses administered were 50 mg on day 5 and 100 mg on day 6 of each treatment period. Comparisons of blood pressure and heart rate changes after tyramine ingestion between moclobemide and placebo conditions did not indicate any relevant moclobemide-tyramine interaction. It is concluded that tyramine in quantities of up to 100 mg does not lead to clinically relevant blood pressure reactions in moclobemide-treated subjects, if moclobemide is taken at the end of the meal.

Administration, Oral↗
PubMed1983

Pharmacokinetic and clinical considerations in the choice of a hypnotic.

Not only has insomnia become much more frequent in the last hundred years but its causes have also changed considerably. In the treatment of insomnia, benzodiazepines--because of their additional anxiolytic effect--offer substantial advantages over other sleep-inducing agents. The residual fraction--the quotient of plasma concentration at 12 h after drug intake to maximum plasma concentration--makes it possible to differentiate between the benzodiazepines according to their suitability as anxiolytics or hypnotics. Midazolam has the lowest residual fraction of all known benzodiazepines and thus, administered in the appropriate dosage, also has the shortest duration of activity.

Anti-Anxiety Agents↗
PubMed1981

Antihypertensive effects of a novel peripheral vasodilator, Ro 12-4713.

The effects of Ro 12-4713, a vasodilator, on blood pressure and heart rate, were tested in 13 ambulant patients with mild to severe hypertension. The patients received Ro 12-4713 in total oral doses ranging from 1.5 to 4 mg/kg over a 3-5 day period. Standard laboratory tests were done 24 h before and after the study. Standing and supine blood pressure and heart rate were determined before, and every hour for 6-8 h after drug administration. ECGs were recorded before, during and at the end of each study day. Ro 12-4713 reduced the pretreatment standing and supine-blood pressure from 213 +/- 34/126 +/- 21 mmHg and 218 +/- 31/130 +/- 20 mmHg to 156 +/- 33/85 +/- 9 mmHg and 158 +/- 25/88 +/- 11 mmHg at the end of Day 5. Heart rate was only transiently increased in patients with pretreatment values of less than 90 beats/min. Although abnormal ECGs tended towards normalization, there were 2 cases of T-wave inversion (the patients remained asymptomatic). Raised BUN levels tended to decrease towards normal. Side effects reported spontaneously by patients (headaches, palpitations, dizziness, nausea and one case of water retention) appeared to be transient in nature. Ro 12-4713 appeared to be a very potent and long lasting antihypertensive agent, whose inherent side effects were only transient in nature.

Aged↗