d-TubocurarineThe origin of neuromuscular blocking agents.
d-Tubocurarine is awesome. It's also known as dTC. It's just 86 (or 87) atoms, but it can easily take down a human. Most of those other nondepolarizing NMBs are just synthetic wannabe molecules made in laboratories. Tubocurarine, on the other hand, is the real thing. It's one of the active ingredients in freaking curare (the other main one being toxiferine). It was originally used to kill people and animals. Now that's an awesome molecule right there. |
The ED95 and normal paralyzing dose for humans is 0.5 mg/kg.
This means that if you had your body weight in d-tubocurarine, it would be enough to paralyze you 2 million times.
Plantae, Magnoliophyta, Magnoliopsida, Ranunculales, Menispermaceae, Chondrodendron tomentosum
It works by binding to acetylcholine receptors and preventing acetylcholine from binding to them. It can also apparently bind to a few other receptors such as GABA, glycine, and 5-HT(3) receptors. This is because those receptors have very similar structures to ACh receptors, also being ion channel proteins with 5 subunits. And you might ask, if it can bind to GABA receptors, why doesn't it cause tetanus or something? The answer is quite simple, GABA receptors are located in the brain, and dTC doesn't cross the blood-brain-barrier, so it never gets the chance. It primarily binds to and blocks nicotinic acetylcholine receptors at the neuromuscular junction, acetylcholine can't bind to receptors to trigger a depolarization and action potential within the skeletal muscles, and you don't move.
DTC is formed through chemical reactions involving dopamine and tyramine. You actually have the ingredients to make dTC floating around in your body right now. Be thankful that you don't actually have the enzymes that make it too. Just remember, every time you eat dairy that has tyrosine that your body will make into tyramine and dopamine, you're eating the ingredients to make dTC. Luckily, you actually can ingest dTC and live... (I don't suggest it; it tastes bad. And if you have any sort of cut or tiny opening on your mouth or gums or something and it gets into your bloodstream...)
It was "officially" used in surgery as a medicine for the first time on January 23, 1942 by Harold Griffith on a 20-year-old male patient undergoing an appendectomy. Before that, people still attempted to use it for surgery, often times without realizing that it had absolutely no effect on consciousness or pain. And before that, they used it during electroconvulsive therapy so that the patient wouldn't be injured due to muscle contractions during the seizure. And even before that, there were many failed attempts at using it to treat disorders such as cerebral palsy and rabies, which usually just resulted in a dead patient. It was first used for killing things way before you were born. The plant itself existed millions of years before you were born. Its order, Ranunculales, is the oldest order of flowering eudicots. d-Tubocurarine the molecule is most likely older than humanity.
The "d" in d-tubocurarine stands for "dextrorotatory." Sometimes, it can be called (+)-tubocurarine, which is just the same as saying "d-." There is such thing as "l" or "levorotatory" tubocurarine, but the "d" variant is more potent and studied and used more often.
There are a few forms of it that one may come across when talking about dTC: a protonated and unprotonated form. The protonated form can exist when dTC is inside the human body, and the second nitrogen can become positively charged with its 3 original bonds to carbon atoms and a new 4th bond to a hydrogen. However, dTC is still seen as a monoquaternary bisbenzyltetrahydroisoquinoline with the chemical formula C37H41N2O6 when it is not protonated (H42 when it is). What I mean by monoquaternary is that it has one quaternary ammonium cation. A quaternary ammonium is a nitrogen bonded to four carbon atoms, and it has a positive charge (I call it the N+ of death). Something that is monoquaternary has one quaternary ammonium, and quaternary ammoniums are permanently charged. The other nitrogen that sometimes has a positive charge is technically not quaternary because not all four bonds are carbon, and the nitrogen is not positively charged if it's not protonated.
There is also a bisquaternary molecule similar to tubocurarine known as metocurine, and it is sometimes called dimethyltubocurarine. According to many websites, metocurine and dimethyltubocurarine are the same thing. However, metocurine has 3 more methyl groups than normal tubocurarine, not 2, as the other name implies.
Metocurine is sometimes incorrectly called dimethyltubocurarine because when scientists first proposed the structure for d-tubocurarine, they believed it had one more methyl group than it actually did. Metocurine was developed shortly after, before they knew the correct structure of dTC, and going off the incorrect structure, metocurine had two more methyl groups that dTC, hence the name dimethyltubocurarine. It wasn't until 1970, many years after metocurine came out, that researchers discovered that dTC had one less methyl group than originally thought. This means that metocurine actually has 3 more methyl groups than dTC. So really, it's trimethyltubocurarine. If you're not sure, just call it metocurine.
But anyways, d-tubocurarine is awesome, and it's easily one of my favorite NMBs.
This means that if you had your body weight in d-tubocurarine, it would be enough to paralyze you 2 million times.
Plantae, Magnoliophyta, Magnoliopsida, Ranunculales, Menispermaceae, Chondrodendron tomentosum
It works by binding to acetylcholine receptors and preventing acetylcholine from binding to them. It can also apparently bind to a few other receptors such as GABA, glycine, and 5-HT(3) receptors. This is because those receptors have very similar structures to ACh receptors, also being ion channel proteins with 5 subunits. And you might ask, if it can bind to GABA receptors, why doesn't it cause tetanus or something? The answer is quite simple, GABA receptors are located in the brain, and dTC doesn't cross the blood-brain-barrier, so it never gets the chance. It primarily binds to and blocks nicotinic acetylcholine receptors at the neuromuscular junction, acetylcholine can't bind to receptors to trigger a depolarization and action potential within the skeletal muscles, and you don't move.
DTC is formed through chemical reactions involving dopamine and tyramine. You actually have the ingredients to make dTC floating around in your body right now. Be thankful that you don't actually have the enzymes that make it too. Just remember, every time you eat dairy that has tyrosine that your body will make into tyramine and dopamine, you're eating the ingredients to make dTC. Luckily, you actually can ingest dTC and live... (I don't suggest it; it tastes bad. And if you have any sort of cut or tiny opening on your mouth or gums or something and it gets into your bloodstream...)
It was "officially" used in surgery as a medicine for the first time on January 23, 1942 by Harold Griffith on a 20-year-old male patient undergoing an appendectomy. Before that, people still attempted to use it for surgery, often times without realizing that it had absolutely no effect on consciousness or pain. And before that, they used it during electroconvulsive therapy so that the patient wouldn't be injured due to muscle contractions during the seizure. And even before that, there were many failed attempts at using it to treat disorders such as cerebral palsy and rabies, which usually just resulted in a dead patient. It was first used for killing things way before you were born. The plant itself existed millions of years before you were born. Its order, Ranunculales, is the oldest order of flowering eudicots. d-Tubocurarine the molecule is most likely older than humanity.
The "d" in d-tubocurarine stands for "dextrorotatory." Sometimes, it can be called (+)-tubocurarine, which is just the same as saying "d-." There is such thing as "l" or "levorotatory" tubocurarine, but the "d" variant is more potent and studied and used more often.
There are a few forms of it that one may come across when talking about dTC: a protonated and unprotonated form. The protonated form can exist when dTC is inside the human body, and the second nitrogen can become positively charged with its 3 original bonds to carbon atoms and a new 4th bond to a hydrogen. However, dTC is still seen as a monoquaternary bisbenzyltetrahydroisoquinoline with the chemical formula C37H41N2O6 when it is not protonated (H42 when it is). What I mean by monoquaternary is that it has one quaternary ammonium cation. A quaternary ammonium is a nitrogen bonded to four carbon atoms, and it has a positive charge (I call it the N+ of death). Something that is monoquaternary has one quaternary ammonium, and quaternary ammoniums are permanently charged. The other nitrogen that sometimes has a positive charge is technically not quaternary because not all four bonds are carbon, and the nitrogen is not positively charged if it's not protonated.
There is also a bisquaternary molecule similar to tubocurarine known as metocurine, and it is sometimes called dimethyltubocurarine. According to many websites, metocurine and dimethyltubocurarine are the same thing. However, metocurine has 3 more methyl groups than normal tubocurarine, not 2, as the other name implies.
Metocurine is sometimes incorrectly called dimethyltubocurarine because when scientists first proposed the structure for d-tubocurarine, they believed it had one more methyl group than it actually did. Metocurine was developed shortly after, before they knew the correct structure of dTC, and going off the incorrect structure, metocurine had two more methyl groups that dTC, hence the name dimethyltubocurarine. It wasn't until 1970, many years after metocurine came out, that researchers discovered that dTC had one less methyl group than originally thought. This means that metocurine actually has 3 more methyl groups than dTC. So really, it's trimethyltubocurarine. If you're not sure, just call it metocurine.
But anyways, d-tubocurarine is awesome, and it's easily one of my favorite NMBs.