The dietary constraints have been overhyped, but people have died of strokes on MAOIs. The 6mg EMSAM essentially requires no diet, more so for the 9mg and 12mg versions. But as told EMSAM is less effective than Parnate. I was a full-out insomniac on EMSAM. Not so on Parnate. Mileage varies, of course.
TCA's have lots of peripheral effects. This is from wikipedia, but generally shows how diverse their mechanisms can be:
The mechanisms of imipramine's actions include, but are not limited to, effects on:
Serotonin: very strong reuptake inhibition.
Norepinephrine: strong reuptake inhibition. Desipramine has more affinity to norepinephrine transporter than imipramine.
Dopamine: imipramine blocks D2 receptors.[28] Imipramine, and its metabolite desipramine, have no appreciable affinity for the dopamine transporter (Ki = 8,500 and >10,000 nM, respectively).[29]
Acetylcholine: imipramine is an anticholinergic, specifically an antagonist of the muscarinic acetylcholine receptors. Thus, it is prescribed with caution to the elderly and with extreme caution to those with psychosis, as the general brain activity enhancement in combination with the "dementing" effects of anticholinergics increases the potential of imipramine to cause hallucinations, confusion and delirium in this population.
Epinephrine: imipramine antagonizes adrenergic receptors, thus sometimes causing orthostatic hypotension.
Sigma receptor: activity on sigma receptors is present, but it is very weak (Ki = 520 nM) and it is about half that of amitriptyline (Ki = 300 nM).[citation needed]
Histamine: imipramine is an antagonist of the histamine H1 receptors.
BDNF: BDNF is implicated in neurogenesis in the hippocampus, and studies suggest that depressed patients have decreased levels of BDNF and reduced hippocampal neurogenesis. It is not clear how neurogenesis restores mood, as ablation of hippocampal neurogenesis in murine models do not show anxiety related or depression related behaviours.
Chronic imipramine administration results in increased histone acetylation (which is associated with transcriptional activation and decondensed chromatin) at the hippocampal BDNF promotor, and also reduced expression of hippocampal HDAC5.[30][31]
