Search PubMedSearch

Biomedical subjects

S K Ahmed

Publications and source records attributed to S K Ahmed.

3 recordsLinked to original sources

Reversible and selective inhibitors of monoamine oxidase A in the treatment of depressed elderly patients.

The treatment of depression in the elderly population needs a thorough and careful work-up and an aggressive therapeutic approach. Any treatment initiative in this population often becomes difficult because of accompanying physical illness, concomitant medication, possible degenerative changes in central nervous system and age-related altered metabolic status. Despite unevenness in research findings, pharmacological treatment remains the mainstay of management of depression among elderly people. Currently available antidepressants, although effective, are problematic because of the increased vulnerability of the elderly to side effects. Recent research efforts to improve the efficacy and safety of drug treatment of depression resulted in development of reversible and selective monoamine oxidase inhibitors of the isoenzyme A (RIMA), with antidepressant efficacy comparable to tricyclic antidepressants and newer generation antidepressants. RIMAs include moclobemide, brofaromine, toloxatone and cimoxatone. Moclobemide is the most investigated available RIMA for therapeutic use at present. Its absorption and disposition in elderly individuals do not differ significantly from those in young healthy volunteers and depressed patients. The results of present clinical studies show that, in elderly depressed patients, moclobemide is at least as effective as other antidepressants. Its particular advantage is, however, that it is as well tolerated in elderly people as in younger people. There are only few significant adverse events, and they are generally less frequent and less severe than those with TCAs. An additional attribute of moclobemide seems also to be its beneficial effect on cognitive functions.

Aged

Biochemistry and pharmacology of reversible inhibitors of MAO-A agents: focus on moclobemide.

Moclobemide, p-chloro-N-[morpholinoethyl]benzamide, is a prototype of RIMA (reversible inhibitor of MAO-A) agents. The compound possesses antidepressant efficacy that is comparable to that of tricyclic and polycyclic antidepressants. In humans, moclobemide is rapidly absorbed after a single oral administration and maximum concentration in plasma is reached within an hour. It is moderately to markedly bound to plasma proteins. MAO-A inhibition rises to 80% within two hours; the duration of MAO inhibition is usually between eight and ten hours. The activity of MAO is completely reestablished within 24 hours of the last dose, so that a quick switch to another antidepressant can be safely undertaken if clinical circumstances demand. RIMAs are potent inhibitors of MAO-A in the brain; they increase the free cytosolic concentrations of norepinephrine, serotonin and dopamine in neuronal cells and in synaptic vesicles. Extracellular concentrations of these monoamines also increase. In the case of moclobemide, increase in the level of serotonin is the most pronounced. Moclobemide administration also leads to increased monoamine receptor stimulation, reversal of reserpine induced behavioral effects, selective depression of REM sleep, down regulation of beta-adrenoceptors and increases in plasma prolactin and growth hormone levels. It reduces scopolamine-induced performance decrement and alcohol induced performance deficit which suggest a neuroprotective role. Tyramine potentiation with moclobemide and most other RIMA agents is negligible.

Benzamides