A brain... It's actually about how to get a molecule into the brain.
(this is a previous log _ (: writing "∠))
the cause of opening this brain hole is a joke:
" once upon a time there was a medical student who found a blank in his mind after reciting. He thought, well, knowledge has been integrated into the blood. as a result, when he took the exam, he found that the macromolecule of knowledge could not pass the blood-brain barrier! Later, he broke the book into knowledge points, and after he memorized it, he still found a blank in his mind. He thought, well, the knowledge had been integrated into the blood. As a result, when he took the exam, he found that the small molecule of Nima knowledge had been filtered into the urine through the glomerulus! "
here, we treat "knowledge" as a kind of molecule, and then talk about some knowledge about the distribution and excretion of molecules in the body, so as to resonate with medical students. OTZ
so, if "knowledge" is really a molecule, how do you get it to the brain?
first of all, we need to know about the blood-brain barrier. The spinal cord and brain are the most important headquarters of the human body, so of course you can't just let it through. The blood-brain barrier is responsible for blocking the blood and the central nervous system, where the capillary endothelium connects more closely, there is a basement membrane outside the endothelial cells, and there are glial cells outside the basement membrane, and the pinocytosis here is very weak. active transport is also limited to a small number of substances necessary to maintain life, and drugs generally rely on free diffusion if they want to pass through them.
first of all, as mentioned in the original text, it is very important to control the molecular weight of drugs, and the knowledge points of small molecules are obviously much more advantageous than the large pieces of knowledge they aggregate to form. However, even the knowledge of small molecules is not guaranteed to pass through the blood-brain barrier, but it is possible, as mentioned above, to flow down the urine before it works. What should we do at this time?
small molecules that cannot pass through the blood-brain barrier and are excreted through the kidneys actually point to the same properties of the substance: greater polarity and good water solubility. Generally speaking, high polarity and good water solubility are conducive to the excretion of substances from the kidneys, and sometimes in order to facilitate the excretion of certain substances, its chemical structure is also modified to increase water solubility (for example, a common way is glucuronidation in the liver).
but if you want to travel freely at both ends of the blood-brain barrier, you need the opposite properties: the polarity of the molecule should be small, and it has a good affinity with lipids. In that case, if we want to let the small molecular knowledge that can not enter the brain cross the blood-brain barrier smoothly, we can change the chemical structure appropriately and reduce the polarity. There are many examples of this transformation, but the two examples that come to my mind at the moment do not seem to be very positive: one is heroin, which is the product of acetylation of morphine, resulting in an increase in fat solubility. more go to the brain to play a role, the analgesic effect is quite powerful in a short period of time, but the addiction becomes more and more serious. The other is methamphetamine, which removes one of the hydroxyl groups from the ephedrine molecule, so the molecular polarity decreases and the fat solubility increases. As a result, ephedrine does not have much central nervous excitability, while methamphetamine makes people high every minute. In many cases, the structural modification of drugs will be reversed, that is, to increase the polarity of molecules so that they can not enter the brain. The advantage of this is to reduce the side effects associated with the central nervous system. For example, the common anti-allergy drugs in life are like this. Generally speaking, we feel sleepy when we take cold medicine, because anti-allergic ingredients such as chlorpheniramine and diphenhydramine are added to the compound cold medicine, which can help relieve symptoms such as sneezing and runny nose. but when they enter the central nervous system, they show lethargic side effects. Later, there are modified new anti-allergy drugs, with greater molecular polarity and fewer drugs entering the center, which will make people less drowsy, and some new anti-allergy drugs can even be taken without affecting the safety of driving.
sometimes, even molecules with less polarity or molecular weight can enter the blood-brain barrier, which is when there is something wrong with the blood-brain barrier itself. When the meninges are inflamed, the permeability of the blood-brain barrier will increase, and some substances that can not enter can also take advantage of the deficiency. This is not a good thing, but we can also use it, such as some drugs to treat infection, they may not be able to pass through the usual blood-brain barrier, but as long as they can take advantage of it at this time, they can be used to treat meningitis, so that there are more options for treatment.
in addition, there is a simple and crude ultimate method-- a direct and forced breakthrough. It doesn't matter if you can't cross the blood-brain barrier. I'll send you directly to the cerebrospinal fluid so that there is no hindrance in reaching the brain. If the drug is injected through a lumbar puncture (this is called intrathecal injection), the drug can reach the cerebrospinal fluid directly. This traumatic method is not often used, but there is also a more common example of using this method to deal with leukemia that invades the central nervous system.
Let's talk so much first. The next time knowledge can't get into your head, do you know what to do ~ (: knowledge "∠) _
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