In the field of drug discovery, classical pharmacology,[1] also known as forward pharmacology,[2][3][4] or phenotypic drug discovery (PDD),[5] relies on phenotypic screening (screening in intact cells or whole organisms) of chemical libraries of synthetic small molecules, natural products or extracts to identify substances that have a desirable therapeutic effect. Using the techniques of medicinal chemistry, the potency, selectivity, and other properties of these screening hits are optimized to produce candidate drugs.
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Types of neurotransmitters | Nervous system physiology | NCLEX-RN | Khan Academy
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Types of neurotransmitter receptors | Nervous system physiology | NCLEX-RN | Khan Academy
Transcription
Voiceover: In this video I want to talk about the different types of neurotransmitters. Neurotransmitters are molecules that communicate information between neurons and their target cells and chemical synapses. There may be hundreds of different types of neurotransmitters and they can be categorized in a number of different ways, but probably the most common as to divide them up by their molecular structure into amino acids, peptides, monoamines and others. I'm gonna mention a bunch of chemistry terms next. Don't worry about them if you don't know them but if you are interested there are many great videos on these topics on the Khan Academy. The first category of neurotransmitters I'm gonna represent with these three neurotransmitters right here and this category is the amino acids. Amino acid neurotransmitters. Amino acids. That's these three right here. Amino acids have an amino group, this guy right here and they have a carboxylic acid group. This part right here. There are lots of different types of amino acids but just a few of them function as neurotransmitters in the nervous system. The next category of neurotransmitters I'm gonna represent with this one right here and these are the peptides. Peptide neurotransmitters and I'll just have this one representative here. Peptides are actually polymers or chains of amino acids. A bunch of these amino acids get strung together in these chains, these polymers and we call them peptides. Peptides are much larger molecules than all the other types of neurotransmitters. Sometimes people divide up neurotransmitters just into peptides and they lump together all the other neurotransmitters and call them small molecule neurotransmitters. The neurotransmitters in this row will represent our next big category which are the monomines. Monoamine neurotransmitters, monoamines. That's this whole row. I've picked out five representative neurotransmitters for the monoamines. These are also sometimes called biogenic amines. Either monoamines or biogenic amines. The monoamines are organic molecules with an amino group here and here and here, here and here connected to an aromatic group here, here, here, here and here. The amino group and aromatic group are connected by a two carbon chain, this part here and here and here, here and here. Some of the monoamines, these three. Draw little stars next to these three, are also called by a different name and that name, and let me draw a little star. That name is the catecholamines. Catecholamines. Catecholamines are a subgroup of the monoamines and the catecholamines have a catachol group which is this part right here which has a benzine, this ring and two hydroxyl groups. Here's one hydroxyl group and here's another hydroxyl group. This catechol group, all the catecholamines have this group these three right here. There are many other types of neurotransmitters that are not amino acids or monoamines or peptides and this neurotransmitter right here is gonna be the representative for that. I'll just call this category other. These are the other molecular types of neurotransmitters. Now I'm gonna introduce some important neurotransmitters in these different groups and I'm gonna mention some of their functions. Don't worry too much about their functions right now because they do so many different things in different parts of the nervous system that we'll come back to all of that in other videos. I just want to briefly introduce the different important neurotransmitters in each of these classes. Starting with the amino acids. Important amino acid neurotransmitters are this one which is called glutamate. Glutamate. This one which is called gamma-aminobutryic acid which pretty much everybody just shortens to GABA. G-A-B-A for gamma-aminobutryic acid. This one which is glycine. Glycine. Glutamate is the most common excitatory neurotransmitter of the nervous system. Let me just draw a big plus sign above glutamate here because most of the time in the nervous system when a neuron is releasing a neurotransmitter that it's exciting its target cell most of the time that neurotransmitter is glutamate because it usually causes depolarization of target cells so that it excites them. GABA and glycine are the most common inhibitory neurotransmitters of the nervous system. Let me just write some big minus signs above GABA and glycine because they usually cause hyper polarization of target cells and inhibit those target cells. GABA is the most common inhibitory neurotransmitter in the brain while glycine is the most common inhibitory neurotransmitter in the spinal cord, so that the amino acid neurotransmitters are really involved in most functions of the nervous system. Pretty much if you think of anything the nervous system is doing at some point in the chains and networks of neurons glutamate, GABA and/or glycine are probably involved in moving information through those networks. There are many important monoamine neurotransmitters but I'm just gonna mention these five that are arguably the most important. The first one here is serotonin. Serotonin. The next one here is histamine. Histamine. The next one is called dopamine. Dopamine. Then this one is epinephrine. Epinephrine. Right next to epinephrine is its close cousin norepinephrine. Norepinephrine. All five of these are monoamine neurotransmitters but these three dopamine, epinephrine and norepinephrine are also called catecholamines. The monoamines play a lot of different functions in the nervous system and in particular a lot of functions of the brain including big things like consciousness, inattention and cognition or thinking, and emotions or us having feelings. Norepinephrine is also released by some autonomic neurons in the peripheral nervous system. Many disorders of the nervous system involve abnormalities of these monoamine neurotransmitters systems, and many drugs that people commonly take affect the monoamine neurotransmitters. There are many important peptide neurotransmitters including a group of peptide neurotransmitters called the opioids. Opioids. The opioids are a group within the bigger group of the peptide neurotransmitters. This one is one example of an opioid. This is endorphin. Endorphin. The peptide neurotransmitters play a role in many functions of the nervous system but the opioids in particular play a big role in our perception of pain. A number of pain medications affect the opioid neurotransmitters. Last but definitely not least are the other neurotransmitters. Usually when there's an other category of anything that means it's not very important but in the case of neurotransmitters there are some really important neurotransmitters that are not amino acids, monoamines or peptides. For example, this neurotransmitter right here is called acetylcholine. Acetylcholine. Acetylcholine is definitely one of our most important neurotransmitters. It does a number of functions in the central nervous system, and then in the peripheral nervous system it's released by most neurons in the autonomic nervous system. Let me just right ANS for autonomic nervous system and it's released by neurons called motor neurons that synapse on skeletal muscle and tell our skeletal muscle to contract to make us move. Again, don't worry too much about these functions because in other videos we'll go more into the structure and the function of the nervous system and talk about specific neurotransmitter pathways. I just wanted to introduce the different types of neurotransmitters here and start to give you a feel for the huge variety of functions all these different neurotransmitters have in the nervous system.
Historical background
Classical pharmacology traditionally has been the basis for the discovery of new drugs. Compounds are screened in cellular or animal models of disease to identify compounds that cause a desirable change in phenotype. Only after the compounds have been discovered, an effort is made to determine the biological target of the compounds through target validation experiments often involving chemoproteomics. More recently it has become popular to develop a hypothesis that a certain biological target is disease modifying and screen for compounds that modulate the activity of this purified target. Afterwards, these compounds are tested in animals to see if they have the desired effect. This approach is known as "reverse pharmacology"[1] or "target based drug discovery" (TDD).[5] However, recent statistical analysis reveals that a disproportionate number of first-in-class drugs with novel mechanisms of action come from phenotypic screening,[6] which has led to a resurgence of interest in this method.[7]
Similarity with pharmacognosy
Pharmacognosy, the investigation of botanics used in indigenous medical traditions is essentially classical pharmacology. Pharmacognosy and classical pharmacology are both often contrasted with reverse pharmacology, that is, working from the target backward to identify new drugs starting with screening libraries of compounds for affinity for particular target. In pharmacognosy, folk medicines are first tested in clinical trials for efficacy. Only after efficacy has been established, is an effort made to determine the biologic target of the drug.
See also
References
- ^ a b Takenaka T (September 2001). "Classical vs reverse pharmacology in drug discovery". BJU Int. 88 Suppl 2: 7–10, discussion 49–50. doi:10.1111/j.1464-410X.2001.00112.x. PMID 11589663. S2CID 30711746.
- ^ Lazo JS (April 2008). "Rear-view mirrors and crystal balls: a brief reflection on drug discovery". Mol. Interv. 8 (2): 60–3. doi:10.1124/mi.8.2.1. PMID 18403648.
- ^ Bachmann KA, Hacker MP, Messer W (2009). Pharmacology principles and practice. Amsterdam: Elsevier/Academic Press. p. 576. ISBN 978-0-12-369521-5.
- ^ Vogt A, Lazo JS (August 2005). "Chemical complementation: a definitive phenotypic strategy for identifying small molecule inhibitors of elusive cellular targets". Pharmacol. Ther. 107 (2): 212–21. doi:10.1016/j.pharmthera.2005.03.002. PMID 15925410.
- ^ a b Lee JA, Uhlik MT, Moxham CM, Tomandl D, Sall DJ (May 2012). "Modern phenotypic drug discovery is a viable, neoclassic pharma strategy". J. Med. Chem. 55 (10): 4527–38. doi:10.1021/jm201649s. PMID 22409666.
- ^ Swinney DC, Anthony J (July 2011). "How were new medicines discovered?". Nat Rev Drug Discov. 10 (7): 507–19. doi:10.1038/nrd3480. PMID 21701501. S2CID 19171881.
- ^ Kotz J (April 2012). "Phenotypic screening, take two". Science-Business EXchange. 5 (15): 380. doi:10.1038/scibx.2012.380.
This page was last edited on 22 July 2022, at 20:39