Antidepressants - neuropharmacology Flashcards
In general, how do antidepressants work?
By increasing activity of one or more MA systems of the brain.
What are the two types of first generation antidepressants?
Monoamine Oxidase Inhibitors (MAOIs) Tricyclic antidepressants (TCAs)
What is Monoamine Oxidase (MAO)?
An enzyme that degrades MA molecules that float freely (i.e. outside vesicles, usually in the synapse), thus depleting available NT.
How do MAOIs work?
They block the activity of MAO so that molecules of DA, NE, and 5-HT that float freely are not destroyed but, instead, are available for vesicle storage and later release. Thus, MAOIs increase the availability and activity of of DA, NE, and 5-HT
What are the two types of MAO?
MAO-A and MAO-B
MAO-A: Degrades all three MAs
MAO-B: most active in metabolizing DA.
Explain the differences between older and newer first generation antidepressants.
Older: Nonselective of which MAO they bind to (MAO-A & MAO-B), and irreversible effects (takes weeks for normal MAO functioning to return after you stop taking the MAOI)
Newer: E.g. Seligiline. Act selectively on MAO-B at low doses and MAO-A at higher doses. Some newer MAOIs effects are reversible, i.e. they can detach from MAO rather than deactivate it permanently.
Explain the mechanism of action for TCAs.
Similar to second generation antidepressants such as SSRIs and SNRIs.
Block reuptake transporter proteins on the terminal buttons of 5-HT and NE neurons so that, after these monoamines are released into the cleft by an action potential, their reuptake is inhibited and their duration of action on the postsynaptic cell is prolonged.
What other systems do TCAs interact with? What can this cause?
Act as anticholinergics, blocking muscarinic acetylcholine receptors, and they antagonize histamine and alpha 1 adrenergic receptors. TCAs are often safer and more effective than MAOIs, but these additional actions can produce unpleasant and even dangerous side effects in some people.
What are the classes of drugs in the second and third generation antidepressants?
SSRIs, SNRIs, and atypicals.
Explain the mechanism of action for SSRIs
Block the reuptake transporter proteins and diminish the ability of presynaptic cells to reabsorb and recycle 5-HT. This causes a buildup of 5-HT at synapses and prolongs postsynaptic receptor stimulation.
What receptors do SSRIs bind to?
They are not selective of which 5-HT receptors they bind to. But it is believed that the antidepressant effects of the SSRIs result from changes to 5-HT1A receptor functioning whereas the unpleasant side effects of the SSRIs may be due to activation of 5-HT2 receptors.
Explain the mechanism of action for SNRIs and atypicals.
Block the reuptake of 5-HT, NE, and in some cases DA.
E.g. Bupropion, Mirtazapine
What is Bupropion, how does it work?
A second or third generation antidepressant.
Blocks DA reuptake transporter proteins, used to treat depression and a smoking cessation aid. Also affects the functioning of NE and ACh.
What is Mirtazapine, how does it work?
Second or third generation antidepressant.
Antagonizes autoreceptors, specifically for NE and 5-HT, prevents inhibitory feedback to the cell and thereby increases the amount of NT released.
Also (along with other atypicals) blocks histamine receptors to induce sedation and drowsiness in those individuals who experience ifficulty falling and staying asleep.
