Monoamine oxidase inhibitors anxiolytics

A number of medications used in the treatment of anxiety have effects on serotonin neurotransmission (Ch. 13). These medications include tricyclic antidepressant medications, SSRIs, and monoamine oxidase inhibitors (MAOIs). However, because these medications take weeks to exert their full anxiolytic effects, it is unlikely that blocking the reuptake (and thus increasing synaptic levels) of either serotonin or norepinephrine selectively is responsible for their anxiolytic properties — rather it is suspected that the therapeutic effects are due to changes in gene expression, protein levels, and eventually changes in synaptic connections between neurons. 

Monoamine Oxidase inhibitors (MAOis). Developed in the 1950s, the MAOIs were the first class of antidepressants. Subsequently, in the 1960s, the MAOis were also found to be effective anxiolytics. Unlike benzodiazepines and barbiturates, the MAOis are not addictive however, their onset of action is delayed not by minutes or hours but by 3 weeks or more. 

Examples of monoamine oxidase inhibitors are phenelzine, tranylcypromine, isocarboxazid and mo-clobemide. They are indicated for atypical depression. Changes in the neurotransmitter levels are seen in several days but the clinical effect may lag by several weeks. Phenelzine is a non-selective hydrazine-type monoamine oxidase inhibitor while the also non-selective inhibitor tranylcypromine is of the non-hydrazine-type. Phenelzine, tranylcypromine and isocarboxazid are irreversible inhibitors. Phenelzine is partly metabolized by acetylation and slow acetylators are more prone to toxicity. It has anxiolytic properties and superior efficiacy in treating severe anxiety. 

Morphine and other opioids exhibit intense sedative effects and increased respiratory depression when combined with other sedatives, such as alcohol or barbiturates. Increased sedation and toxicity are observed when morphine is administered in combination with the psychotropic drugs, such as chlorpromazine and monoamine oxidase inhibitors, or the anxiolytics, such as diazepam. 

It became obvious, however, that psychostimulants were not effective in situations of lowered arousal resulting from mood depression. In the 1950s, antidepressants such as the monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) became recognized as more effective in treating depression. The differentiation between arousal and mood thus became clearer. It is through the action of drugs that sedate and thus reduce anxiety versus those drugs that do not sedate but are anxiolytic that the basic concepts of anxiety have forcibly to be reconsidered. This inevitably led to the need for a reconceptualization of psychotropic modes of action in relation to psychiatric disorders. 

Drugs and chemicals are known to cause activated interaction. The depressant action of opioid drugs is enhanced by drugs acting on the central nervous system (CNS) such as alcohol, anesthetics, anxiolytics, hypnotics, tricyclic antidepressants, and antipsychotics. Concomitant administration of opioid analgesics and monoamine oxidase inhibitors (MAOIs) should be avoided, or extra care should be taken if such a therapy is inevitable. Fatal reactions are reported when treated along with selegiline. Interactions also are reported with cyclizine, cimetidine, mexiletine, cisapride, metoclopramide, or domperidone. 

By the 1970s and early 1980s it was recognized that certain tricyclic antidepressants and monoamine oxidase (MAO) inhibitors were effective in treating panic disorder and one tricyclic antidepressant (clomipramine) was effective in treating obsessive-compulsive disorder. Thus, there began to be recognized that some antidepressants overlapped with anxiolytics for the treatment of anxiety disorder sub-types or for mixtures of anxiety and depression (Fig. 8—8). However, either anxiolytics... 

Minor neuroprotector at ischemia [318-320], anxiolytic activity [321], inhibitor of monoamine oxidase [322], inhibitor of neuronal nitric oxide synthesis 323, 324] Trichomonicide [325], insecticides [326]... 

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