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lüll Biochemistry and pharmacology of reversible inhibitors of MAO-A agents: focus on moclobemide Nair NP; Ahmed SK; Kin NMJ Psychiatry Neurosci 1993[Nov]; 18 (5): 214-25Moclobemide, 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/adverse effects/*pharmacokinetics/therapeutic use[MESH]|Brain/drug effects/enzymology[MESH]|Depressive Disorder/drug therapy/*enzymology/psychology[MESH]|Dose-Response Relationship, Drug[MESH]|Humans[MESH]|Isoenzymes/antagonists & inhibitors/blood[MESH]|Metabolic Clearance Rate/physiology[MESH]|Moclobemide[MESH]|Monoamine Oxidase Inhibitors/adverse effects/*pharmacokinetics/therapeutic use[MESH]|Monoamine Oxidase/*blood[MESH]|Neurotransmitter Agents/physiology[MESH] |