Molecules: You'd better learn to live with them.
Yesterday's mention of tyramine, and the comment, reminded me of inhibitors in general, and one in particular: harmine. Harmine belongs to a class of MAOIs known as the beta-carbolines.
MAOIs are problematic because they inhibit the metabolism of certain (toxic in the absence of gastrointestinal MAO) chemicals such as tyramine. Certain MAO enzymes, active in the gut, process these chemicals (ingested through foods such as cheese and wine, as mentioned yesterday). Oral MAOI-class antidepressants act as inhibitors of this enzyme. They aren't used much these days, because of newer antidepressants (including the SSRIs, such as Prozac and Paxil) that don't have the same side effects. However, sometimes they do the job other drugs just can't. A drug called Emsam is a transdermal patch that inhibits MAO, isn't absorbed by the gut, and therefore doesn't have the deleterious MAOI side effects (to the same extent).
Perhaps more interesting, though, are the people that take MAOIs in the absence of symptoms, recreationally. A tea, known colloquially as ayahuasca, contains dimethyltryptamine and beta-carboline alkaloids.
Apparently, this brew contains both harmine and dimethyltryptamine, allowing a chemical that is otherwise inactive orally due to MAO metabolism (dimethyltryptamine) to have psychoactive effects due to the presence of a MAOI (beta-carbolines such as harmine).
See you tomorrow.
Comments
very cool... I have an adrenergics pharm exam (among other subjects) on Friday and we've been talking about tyramine and MAOI interactions. Apparently, when the MAOIs came out they worked well as an antidepressant but there was an increase of people coming into ERs with massive cerebral hemorrhage. An English pharmacist (I think) put two and two together when he realized that many of these new patients were on the MAOIs and had been drinking beer/eating cheese... What was happening is the unoxidized tyramine displaces NE (+ dopamine and serotonin) out of sympathetic presynaptic terminals. The alpha1 receptors in the brain vasculature are fired up, pressure rises dramatically, and the vessel ruptures.
Here's the interesting part - like you said, they are not often prescribed anymore. A depressed patient, when told of the reasons they shouldn't drink beer/eat cheese with their medication, are basically given then tools to commit suicide.
Posted by: heet | September 12, 2006 11:33 PM