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.
The effects of high single doses of moclobemide (300, 450 and 600 mg given at the end of a standardized meal) on plasma levels of several catecholamines and their deaminated metabolites, and on plasma levels of pituitary hormones were determined in eight healthy young male volunteers in a randomized, double-blind, placebo-controlled study. Assessment of the i.v. tyramine potentiation and determination of the plasma levels of moclobemide were also performed. The tyramine sensitivity factor at 2 h after dosing was about 2.1, with no significant differences between the doses used. The inhibitory activity of moclobemide on MAO-A was reflected in significant reductions of plasma concentrations of DHPG and 5-HIAA. No clear differences were detected between the moclobemide doses. Prolactin plasma concentrations were only slightly increased after the two higher doses. The plasma concentrations of moclobemide were very much in agreement with those found in previous studies under similar experimental conditions. Thus, single oral doses of 300, 450 and 600 mg moclobemide demonstrated marked inhibition of MAO-A activity, whereas a single dose of 300 mg induced a near-maximum effect.
Synthesis of a homologous steroidal l7p-pyrrolinone. -Sumwzury. We describe the synthesis of ~1-'-[(3~-Hydroxy-androst-5-en-17~-yl)methyl]-3'-pyrrolin-2'-one (15) starting from 3j3-acetoxy-23-diazo-21,24-dinorchol-6-en-22-one (1).
In a pharmacological screen on drug-drug interactions performed in laboratory animals moclobemide potentiated at high doses the antiphlogistic/anti-inflammatory activity of ibuprofen. Therefore, a study was undertaken to determine in healthy volunteers the faecal blood loss induced by multiple doses of ibuprofen (600 mg t.i.d.) in presence and absence of steady-state concentrations of concomitantly administered moclobemide (150 mg t.i.d.). The results show that multiple doses of moclobemide do not change faecal blood loss induced by ibuprofen. Furthermore, no clinically relevant pharmacokinetic interaction between the two drugs studied was detected.
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