PsychBabel

Like mirtazapine, bupropion’s mechanisms of action are a bit convoluted.

Although it has relatively mild binding affinities for dopamine and norepinephrine reuptake pumps (at usually prescribed doses), bupropion is postulated to have its antidepressant effect through the antagonism of these pumps. Binding at other sites is even lower. Bupropion’s side effects of tremors and sweating are consistent with increased levels of dopamine and norepinephrine.

It appears, therefore, that bupropion’s metabolites play a role in its pharmacologic activity. Bupropion has several active metabolites, and their clearance is slower. The total concentration of bupropion with its metabolites likely accounts for the overall effect of increasing dopamine and norepinephrine.

With information from: Bupropion: What Mechanism of Action? Sheldon H Preskorn, MD. Journal of Practical Psychiatry and Behavioral Health, January 2000, 272-276.

So I always get confused about the details of mirtazapine’s mechanisms of action. I’m not sure what my mental block is. Time to review.

Mirtazapine’s likely antidepressant action is due to antagonism of the presynaptic alpha-2 adrenergic receptors. This should allow for the greater release of serotonin and norepinephrine.

However, mirtazapine’s most potent activity is antagonism of histamine-1 receptors (thus, the sedation). At higher doses, mirtazapine also blocks 5HT2A, 5-HT2C, and 5-HT3 receptors. Antagonism of alpha-2 receptors actually comes last with increasing dosage.

Interestingly, agonism of 5-HT2A, 5-HT2C, and 5-HT3 receptors may be related to the adverse effects of SSRIs: sleep disturbance (5-HT2A), anxiety and weight gain (5-HT2C), and nausea/loose stools/vomiting (5-HT3). Therefore, the antagonist effects of mirtazapine at these sites may mitigate some of the adverse effects of the SSRIs.

With information from: Imipramine, Mirtazapine, and Nefazodone: Multiple Targets. Sheldon H Preskorn, MD. Journal of Practical Psychiatry and Behavioral Health, March 2000, 97-102.