Centanafadine as a possible euphoretic

[Metribolone]

Centanafadine is a “new” drug currently in phase 3 clinical trials as a treatment for adhd in the form of a sustained release tablet to be taken 2 times a day. It is a triple reuptake inhibitor of norepinephrine, dopamine, and serotonin in that order. You can find more information with the patent number WO2013019271A1 which details its synthesis, reuptake values, and more relating to its pharmacology. It was introduced by Otsuka pharmaceutical company as a medication that would have stimulant benefits by working rapidly (as opposed to atomoxetine which takes a couple weeks for the full benefit to take effect) while increasing tolerability similar to non-stimulants.

According to the research it said it has low abuse potential by testing the spontaneous locomotion of rats, but it also attenuated locomotion similar in effectiveness to methylphenidate when tested in the rat model for adhd. It also increased monoamine concentrations significantly both orally and parentally (in immediate release form) reaching peak concentration in about 40 minutes and levels were sustained for 3-4 hours before dropping off.

In current human trials the side effects are similar to similar to both stimulants and antidepressants which includes appetite suppression, dry mouth, nausea, abdominal pain, fatigue and somnolence, rash, headache, and diarrhea when used orally in the sustained release form for a total of either 200 or 400 milligrams a day. Increased dosages had similar tolerability to low dosages.

given this information, do you guys think that it could possibly have euphoric effects while lacking significant stimulant effects when taken in “immediate release” forms such as sniffing the powder, injecting it, or taking it orally. Do you think this would have mild stimulant effects or any at all? Or do you think it would be similar to sniffing an antidepressant providing almost no recreational value even though it would still produce effects?

Overall it looks like a very interesting compound.

 

[Metribolone]

I assume that it would have effects similar to methylphenidate but possibly more euphoric or enjoyable do to the serotonin reuptake inhibitions. I think the serotonin reuptake inhibition is also why it could be more sedating or produce less spontaneous locomotion in rats than traditional stimulants. Also seeing as it kicks in rapidly, being dosed as sustained release by the company, and other patents going over other formulations including a combination of immediate and delayed release beads, point to it having stimulant or possible recreational value that’s not being highlighted (or it could be pointed out but there’s so many patents and studies to read that I may not have seen it).

There are antidepressants that come in extended or sustained release forms due to its half life such as Desvenlafaxine and bupropion to provide steady blood concentrations, and wouldn’t really provide any recreational value. (Bupropions significant preference for ne reuptake over dopamine reduces its recreational value)

This also has me wondering, since there is another triple reuptake inhibitor with a more balanced value among its targets called ansofaxine (toludesvenlafaxine), if it possibly has recreational value. Both the compounds I mentioned have significant dopamine reuptake inhibition as opposed to other antidepressants which makes me wonder of its recreational value.

 

[HerrHaber]

Yes, this could be interesting.