SelectiveSpeeding
Greenlighter
- Joined
- Feb 9, 2019
- Messages
- 6
Hello. I have a few questions regarding the metabolic fate of this compound, which I know is a general answer that can be applied to most phenylalkylamine and alkylbenzylamine related structures. I just want to verify that my research has led me to the correct information and that I understand this enough to be able to explain this properly to others.
From what I can gather, the first step (Phase I), catalyzed by cytochrome P450 enzymes (CYP2D6 and or CYP3A4?) is N-dealkylation as the molecule is a secondary amine, which is essentially removal of the isopropyl moiety through the "carbiniolamine" pathway. The α-carbon is hydroxylated resulting in the primary amine (benzylamine) and a ketone (acetone). From there, benzylamine is metabolized by monoamine oxidases primarily MAO-B, which results in benzaldehyde and an ammonia. There's also a less prevalent pathway of N-oxidation of the original compound which would result in the nitrone because the hydroxylamine formed is not stable. I'm unsure of how big of a factor this would be. Primarily, I am focused on Phase 1 at the moment, and I realize that the specifics of enzyme catalysis is a complex topic on it's own with the metabolites and general mechanisms being what I'm worrying about.
If you're wondering why I'm asking about this, then I'll tell you yes it is because of the fabled use of this compound as a "cut" in commercially available methamphetamine being sold in the USA (and worldwide) that is of Mexican origin. I'm really not of the belief that it is, but the idea has become viral in a few places on the web where this drug is discussed, and it is perpetuated without any proof or verification. In response to this phenomenon, I thought it would be useful to educate myself on the fact that this compound's hydrochloride salt is relatively harmless due to rapid metabolism by P450 enzymes and MAO. I imagine that the half life would not be very long (at least not as long as methamphetamine) but there is no published data on this at all. I'm also pretty sure that it's relatively inactive as a drug molecule, but it still is subject to the human biological environment and want to be able to impress upon people that it's not the cause of life's problems and the center of all evil in the universe.
So if there's anything wrong with the understanding of the mechanisms I outlined in the second paragraph, I would like to hear your input and know if I missed anything. I apologize that this thread has to be about a topic that which the macrocosm of does not belong in this section, but I feel like you that frequent this place would be a good group to ask about the mechanisms and kinetics of this substance's metabolism. Thank you for taking the time to read this, as your time is much appreciated.
From what I can gather, the first step (Phase I), catalyzed by cytochrome P450 enzymes (CYP2D6 and or CYP3A4?) is N-dealkylation as the molecule is a secondary amine, which is essentially removal of the isopropyl moiety through the "carbiniolamine" pathway. The α-carbon is hydroxylated resulting in the primary amine (benzylamine) and a ketone (acetone). From there, benzylamine is metabolized by monoamine oxidases primarily MAO-B, which results in benzaldehyde and an ammonia. There's also a less prevalent pathway of N-oxidation of the original compound which would result in the nitrone because the hydroxylamine formed is not stable. I'm unsure of how big of a factor this would be. Primarily, I am focused on Phase 1 at the moment, and I realize that the specifics of enzyme catalysis is a complex topic on it's own with the metabolites and general mechanisms being what I'm worrying about.
If you're wondering why I'm asking about this, then I'll tell you yes it is because of the fabled use of this compound as a "cut" in commercially available methamphetamine being sold in the USA (and worldwide) that is of Mexican origin. I'm really not of the belief that it is, but the idea has become viral in a few places on the web where this drug is discussed, and it is perpetuated without any proof or verification. In response to this phenomenon, I thought it would be useful to educate myself on the fact that this compound's hydrochloride salt is relatively harmless due to rapid metabolism by P450 enzymes and MAO. I imagine that the half life would not be very long (at least not as long as methamphetamine) but there is no published data on this at all. I'm also pretty sure that it's relatively inactive as a drug molecule, but it still is subject to the human biological environment and want to be able to impress upon people that it's not the cause of life's problems and the center of all evil in the universe.
So if there's anything wrong with the understanding of the mechanisms I outlined in the second paragraph, I would like to hear your input and know if I missed anything. I apologize that this thread has to be about a topic that which the macrocosm of does not belong in this section, but I feel like you that frequent this place would be a good group to ask about the mechanisms and kinetics of this substance's metabolism. Thank you for taking the time to read this, as your time is much appreciated.