Long time no post! I got hired to do some writing and editing for a nootropics startup, but i’m finally back! I’m sticking to my theme of writing about the NMDA Receptor, this time explaining why NMDAR Antagonists can anesthetize you, treat your alzheimers, or cure your depression
A Brief Technical Image
The process of teasing out functions of the NMDA Receptor feels a lot like progressing through this “flowchart” (I ask that you ignore the logic of the image, just scan the vibe). Using drugs with this protein complex seems to inherently lead to bizarre phenomena on both the level of the neuron (see; Hebbia, Homeostatica, and Magnesia) and the brain as a whole (see; Elon’s twitter feed). This is evident once you internalize that without NMDA Receptors, you fundamentally could not make self-referential memories, much less exist as a viable organism.
Quandaries
When you start taking two NMDA Receptor antagonists at once, medical wisdom dictates that you’re liable to check into a psych ward within the week. This is wrong… but I can’t really call the thought process itself irrational. After all, most doctors encounter these drugs in the context of, “there’s an ER patient going fucking insane off PCP (an NMDAR antagonist).”
They often forget how they treat the incoming patient, “we’ve got to sedate him! Lets use Ketamine (another NMDAR antagonist).” And this works.
Now, both PCP and Ketamine are dissociative anesthetics, so the first thought is that this is probably just a dose mediated effect. Surely overdosing them on PCP would also work as a chemical restraint… Phencyclidine was used as an anesthetic in the 1950s, but those same side-effects that led to its recreational use still occurred when people woke up from anesthetic doses. People on Ketamine wake up and get confused, but they don’t get violent.
The question here is Why? Why does the category of ‘NMDA Receptor antagonist’ mean nothing!
Microlevel Differences
Subunit Selectivity
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