opinion on bifemelane antidepressant

[asecin]

i was going through various norepinephrine antidepressants when i found this isolated article on an obscure japanese antidepressant; https://en.wikipedia.org/wiki/Bifemelane

"The drug has nootropic, neuroprotective, and antidepressant-like effects in animal models, and appears to enhance the cholinergic system in the brain" thats amazing

any opinions on this from a more professional look? it seems to have gone obscure after the 90s and all the articles are in the 90s. that could be a red flag? even though, i havent seen being discontinued or banned anywhere....

 

[Weltmeister]

non-competitive (irreversible) inhibition of MAO-B (Ki = 46.0 μM)

my first guess would be that this is the reason why. Drugs that irreversibly inhibit MAO dont have the best reputation

 

[asecin]

selegiline and moclobemie are irreversible inhibitors of MAO B but i never had problems with them. what bad reputation? what are you talking about??

 

[Weltmeister]

My guess is that this was a business decision because of the bad reputation MAOIs got because of their food interactions. Most doctors will prescribe SSRIs over a MAOI because theyre perceived as more foolproof and big pharma is more interested in developing drugs that make them money

 

[asecin]

yeah, ive noticed a trend. MAOIs are more asian and european based and SSRIs more american based. there is conflict of interest here. companies like pfizer wont have some french company butting in their business for sure.

 

[Hodor]

yeah, ive noticed a trend. MAOIs are more asian and european based and SSRIs more american based. there is conflict of interest here. companies like pfizer wont have some french company butting in their business for sure.

The only MAOI that is somewhat common as an antidepressant in Europe is Moclobemide (a reversible MAO-A Inhibitor), and even then they'll usually try several SSRI's and SNRI's before prescribing Moclobemide.

The irreversible MAOIs that still enjoy modest popularity in the US (like Phenelzine and Tranylcypromine) are either completely unavailable or only used in *extremely* rare cases involving severe treatment-resistant depression. Off-label use of Selegiline is also very rare (and we don't get the dedicated antidepressant patch formulation, "EMSAM", either).

 

[Hodor]

selegiline and moclobemie are irreversible inhibitors of MAO B but i never had problems with them. what bad reputation? what are you talking about??

Unlike Selegiline, Moclobemide is not an irreversible inhibitor of MAO-B, but a reversible MAOI that is somewhat selective for MAO-A (although there will be some reversible MAO-B inhibition at high doses).

 

[asecin]

interesting. i always thought of selegiline and moclobemide working the same way. i get more side effects from selegiline but not moclobemide. i read selegiline in high doses also inhibits MAO-A though, and i dosed high on that one. do you think its much better safer and just better choice in general to use moclobemide for depression instead of selegiline?
i was always more into selegiline because of its amphetamine like metabolites and its not neurotoxic like amphetamines so its a win to just use that instead of them. but im curious of second opinion, please

 

[CFC]

do you think its much better safer and just better choice in general to use moclobemide for depression instead of selegiline?

Moclobemide is safer because, as pointed out, it's a competitive inhibitor. So it can still be displaced by high concentrations of monoamines. Thus when you eat foods rich in tyramine which displace peripheral NE (and to some extent 5-HT) from storage vesicles, you're less likely to experience a hypertensive crisis. In other words it has a weak pressor effect, so is safer to dispense to people with underlying cardiovascular issues.

For the same reason, it's also not as strong as selegiline, and less useful for resistant depression.

As for Bifemelane, it was/is a very interesting drug, but sadly not approved for use in most countries.

 

[asecin]

im trying to find bifemelane from japan directly, but its difficult to find this stuff anywhere in any form. wow

 

[Hodor]

interesting. i always thought of selegiline and moclobemide working the same way. i get more side effects from selegiline but not moclobemide. i read selegiline in high doses also inhibits MAO-A though, and i dosed high on that one. do you think its much better safer and just better choice in general to use moclobemide for depression instead of selegiline?

High-dose Selegiline = Irreversible Inhibition of *both* MAO-B and MAO-A, so it wouldn't really be that much safer than other irreversible MAOIs.

Moclobemide, OTOH, is pretty safe, but not quite as effective as irreversible MAOIs. Still, compared to SSRIs, high-dose Moclo is considered particularly effective in patients suffering from social anxiety.

i was always more into selegiline because of its amphetamine like metabolites and its not neurotoxic like amphetamines so its a win to just use that instead of them. but im curious of second opinion, please

Selegiline *is* an amphetamine - N-Methyl-N-Propynyl-Levoamphetamine, if you will. When the Propynyl group gets cleaved off, you end up with actual L-Methamphetamine. Unlike the more recreational D-Methamphetamine, L-Methamphetamine gives you a fairly "dirty"-feeling stimulation because it selectively activates adrenaline receptors, whereas D-Methamphetamine causes your neurons to dump massive amounts of neurotransmitters into the synapse (far more pleasant, but also neurotoxic).

 

[asecin]

what about this one; https://en.wikipedia.org/wiki/Teniloxazine

this seems more interesting to me now, again obscure japanese. hmm... i should probably take both of them and play weird obscure japanese games and see how i feel