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.

Potential of moclobemide to improve cerebral insufficiency identified using a scopolamine model of aging and dementia.

After a baseline performance assessment, 28 healthy male volunteers received subcutaneous injections of scopolamine hydrobromide to induce deficits in memory, attention and cognitive processes. Subsequent performance testing established the decrements caused by the scopolamine, and then each subject was given one of 3 investigational drugs including moclobemide, or placebo, according to a latin-square design. Parallel versions of the test procedures were used to assess drug effects on the scopolamine-induced cognitive deficits. Whereas marked and statistically significant impairment was identified 60 min after scopolamine injection, the global analysis revealed statistically significant superiority of moclobemide over placebo at 120 min in relieving the scopolamine-induced decrement in performance. These results show that moclobemide may improve cognition in conditions associated with cholinergic deficit. It may therefore be especially indicated in the treatment of cognitive decline occurring with normal aging, depression in elderly people and Alzheimer's disease.

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.

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.

Pupillary responses to syntactic ambiguity of sentences.

Pupillary responses have proven to be reliable physiological correlates of cognitive effort in a variety of tasks, including language processing. To investigate the relation between psychological and syntactic complexity 20 syntactically ambiguous sentences, balanced for bias, were presented to 16 subjects, while their pupil size was continuously measured. These sentences could be read as verb oriented (syntactically more complex) or object oriented (syntactically less complex). Principal components analysis of pupillary movements revealed that verb-oriented readings, resulted in greater pupillary dilations than object-oriented readings, indicating that syntactically more complex sentences, as determined via a formal grammar, require greater cognitive effort in processing. This is viewed as further evidence for the notion that syntactic and psychological complexity are related. High- and low-bias sentences did not induce comparable differences in pupillary movements, indicating that the "multiple meaning theory" may have to be modified.