Pharmacology: Antidepressants
Questions and Answers
Generally, how do all antidepressants work?
✓ ~~~ All currently available antidepressant drugs *enhance monoamine
neurotransmission* by one of several mechanisms. The most common mechanism is the
inhibition of the serotonin transporter (SERT), the norepinephrine transporter (NET), or
both.
Name the MAO inhibitors.
✓ ~~~ • Isocarboxazid (hydrazine derivative)
✓ • Phenelzine (hydrazine derivative)
✓ • Tranylcypromine (non-hydrazine derivative)
✓ • Selegiline (non-hydrazine derivative)
What are the two kinds of MAO?
✓ ~~~ There are two isozymes of MAO: MAO-A and MAO-B. MAO-A preferentially
deaminates norepinephrine, epinephrine and serotonin. Dopamine and tyramine are
metabolized by both isozymes.
What is the mechanism of action for MAO inhibitors?
✓ ~~~ MAO inhibitors inactivate the enzyme, permitting neurotransmitter molecules to
escape degradation and, therefore, to both accumulate within the presynaptic neuron and
leak into the synaptic space. This is believed to cause activation of norepinephrine and
serotonin receptors, and it may be responsible for the indirect antidepressant action of
these drugs.
Which MAO inhibitors are non-selective and irreversible?
✓ ~~~ Isocarboxazid, phenelzine and tranylcypromine bind irreversibly and nonselectively
to MAO-A and MAO-B.
Which kind of MAO inhibitor is better in treating major depression?
, ✓ ~~~ Experimentally, selective MAO-A inhibitors are thought to be more effective in
treating major depression than type B inhibitors.
Which MAO inhibitor is approved to treat early Parkinson's disease?
✓ ~~~ The MAO-B inhibitor *selegiline* is approved for treatment of early Parkinson's
disease.
What happens with high doses of selegiline?
✓ ~~~ Selegiline has also antidepressant effects, particularly at high doses that also inhibit
MAO-A or yield amphetamine-like metabolites. Selegiline is the first antidepressant
available in a transdermal delivery system.
Do MAO inhibitors have immediate antidepressant effects?
✓ ~~~ No. Although MAO is fully inhibited after several days of treatment, the
antidepressant action of the MAO inhibitors is delayed several weeks.
Which MAO inhibitors may produce insomnia or agitation?
✓ ~~~ Selegiline and tranylcypromine have an amphetamine-like stimulant effects that may
produce agitation or insomnia.
What are the clinical uses of MAO inhibitors?
✓ ~~~ MAO inhibitors are now *rarely used* due to toxicity and potentially lethal food and
drug interactions. Their primary use is in the *treatment of depression unresponsive to
other antidepressants*.
What are the adverse effects of MAO inhibitors?
✓ ~~~ Possible adverse effects of treatment with MAO inhibitors include drowsiness,
orthostatic hypotension, blurred vision, dry mouth, dysuria, and constipation.
How are MAO inhibitors administered?
Questions and Answers
Generally, how do all antidepressants work?
✓ ~~~ All currently available antidepressant drugs *enhance monoamine
neurotransmission* by one of several mechanisms. The most common mechanism is the
inhibition of the serotonin transporter (SERT), the norepinephrine transporter (NET), or
both.
Name the MAO inhibitors.
✓ ~~~ • Isocarboxazid (hydrazine derivative)
✓ • Phenelzine (hydrazine derivative)
✓ • Tranylcypromine (non-hydrazine derivative)
✓ • Selegiline (non-hydrazine derivative)
What are the two kinds of MAO?
✓ ~~~ There are two isozymes of MAO: MAO-A and MAO-B. MAO-A preferentially
deaminates norepinephrine, epinephrine and serotonin. Dopamine and tyramine are
metabolized by both isozymes.
What is the mechanism of action for MAO inhibitors?
✓ ~~~ MAO inhibitors inactivate the enzyme, permitting neurotransmitter molecules to
escape degradation and, therefore, to both accumulate within the presynaptic neuron and
leak into the synaptic space. This is believed to cause activation of norepinephrine and
serotonin receptors, and it may be responsible for the indirect antidepressant action of
these drugs.
Which MAO inhibitors are non-selective and irreversible?
✓ ~~~ Isocarboxazid, phenelzine and tranylcypromine bind irreversibly and nonselectively
to MAO-A and MAO-B.
Which kind of MAO inhibitor is better in treating major depression?
, ✓ ~~~ Experimentally, selective MAO-A inhibitors are thought to be more effective in
treating major depression than type B inhibitors.
Which MAO inhibitor is approved to treat early Parkinson's disease?
✓ ~~~ The MAO-B inhibitor *selegiline* is approved for treatment of early Parkinson's
disease.
What happens with high doses of selegiline?
✓ ~~~ Selegiline has also antidepressant effects, particularly at high doses that also inhibit
MAO-A or yield amphetamine-like metabolites. Selegiline is the first antidepressant
available in a transdermal delivery system.
Do MAO inhibitors have immediate antidepressant effects?
✓ ~~~ No. Although MAO is fully inhibited after several days of treatment, the
antidepressant action of the MAO inhibitors is delayed several weeks.
Which MAO inhibitors may produce insomnia or agitation?
✓ ~~~ Selegiline and tranylcypromine have an amphetamine-like stimulant effects that may
produce agitation or insomnia.
What are the clinical uses of MAO inhibitors?
✓ ~~~ MAO inhibitors are now *rarely used* due to toxicity and potentially lethal food and
drug interactions. Their primary use is in the *treatment of depression unresponsive to
other antidepressants*.
What are the adverse effects of MAO inhibitors?
✓ ~~~ Possible adverse effects of treatment with MAO inhibitors include drowsiness,
orthostatic hypotension, blurred vision, dry mouth, dysuria, and constipation.
How are MAO inhibitors administered?
