Posted by Crotale on June 18, 2008, at 18:30:07
In reply to Re: Clomipramine vs. Nardil, posted by Phoenix1 on June 18, 2008, at 11:20:03
Phoenix,
It seems to me that just because you had a bad reaction to Nardil, doesn't mean a different MAOI (particularly a non-hydrazine MAOI like Parnate or selegiline) would automatically cause the same problem for you. This is based on my own experience.
Clomipramine is a very powerful serotonin-norepinephrine reuptake inhibitor (it's likely that its active metabolite, N-desmethylclomipramine, contributes to its therapeutic effect), but it's true that it does tend to have a lot of side effects. I actually tolerate MAOIs better than TCAs.
If you want to consider a less "dirty" TCA, you might consider one of the secondary amine compounds, like desipramine or nortriptyline. They tend to have milder anticholinergic and sexual side effects compared with their tertiary amine counterparts (e.g., imipramine, amitriptyline). (The active metabolite N-desmethylchlomipramine is the secondary amine counterpart of chlomipramine, but it isn't marketed itself as a separate medication.)
What I mean by secondary and tertiary amines is this:
A tricyclic compound consists of a core "tricyclic" structure (e.g., in imipramine and desipramine, the tricyclic core is iminodibenzyl, while in amitriptyline and nortriptyline it's dibenzocycloheptadiene) plus a side chain. The side chains typically look something like this:
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CH2-CH2-CH2-N(CH2)2
(tertiary amine)or this:
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CH2-CH2-CH2-N(CH3)(H)(secondary amine)
Often the secondary amine drugs are active metabolites of the similar tertiary amine compounds. For example, desipramine is N-desmethylimipraine (DMI); I think nortriptyline is similarly a metabolite of amitriyptyline.
Protriptyline, doxepin, and maprotiline all have modified tricyclic cores. Amoxapine has a very different side chain as well as a modified core structure. Trimipramine has the same iminodibenzyl core as imipramine but a very modified side chain. It's what I'd call a tertiary amine, but its side chain is altered in other ways.
Chlomipramine just adds a chlorine to the iminodibenzyl of imipramine. Doxepin adds an oxygen in the centre ring of the dicycloheptadiene from amitriptyline. Protriptyline is similar to nortriptyline except that there is one point of saturation (double bond) in the centre ring. Maprotiline adds an ethylene bridge across a six-atom centre ring; its side chain is standard secondary-amine. Trimipramine is really just imipramine with an extra methyl on the side chain:
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CH2-CH(CH3)-CH2-N(CH2)2Amoxapine is somewhat different and has some dopamine antagonist activity. Its tricyclic structure is a bit too difficult for me to depict here, and I wasn't able to draw its side chain, which is a ring itself.
(Amoxapine -- actually N-desmethyl-loxapine -- is a secondary amine, which is consistent with its pharmacology: it has very little effect on serotonin uptake.)
Amoxapine's centre ring has multiple points of saturation, as well as a N and a O. It also has a Cl- hanging off one of the side rings.
As I recall, protriptyline and maprotiline tend to be associated with increased risk of adverse effects -- cardiac arrhythmias in the case of protriptyline, seizures in the case of maprotiline. Amoxapine, of course, has some risk of extrapyramidal side effects as a consequence of its antipsychotic (i.e., dopamine antagonist) activity. In general, tertiary amines tend to be more active at the serotonin transporter than secondary amines.
Please tell me if you think this belongs more on PB-Neurotransmitters. I hope it will help people who are trying to decide whether to try a TCA and if so which one.
poster:Crotale
thread:835192
URL: http://www.dr-bob.org/babble/20080617/msgs/835333.html