Neuropharmacology - Aidan Helfant's Digital Garden

up: [[HD 2230 Introduction to Behavioral Neuroscience]] Tags: # Neuropharmacology Pharmacology is the study of how drugs act on the bodies systems and how the body responds to those drugs. To understand drugs effects we must understand how they alter bodily function by interacting with receptors. ### What are the two types of receptors? **Ionotropic:** ^3e38e1 The receptors they bind to can be ionotropic also called ion-gated ion channels that open allowing ion ins when a ligand or its agonist bind to it. Generally their effects are faster because they signal directly with ions. **Metabotropic:** ^81cc80 ![[Pasted image 20220907101434.png]] Metabotropic channels don't open to allow ions through but they may contain secondary ==G protein== messengers that will affect behavior if the correct ligand or agonist binds. These proteins can have two effects on the postsynaptic cell: 1. They can bind to ionotropic channels and change the way they work possibly opening them. 2. They can stimulate G proteins that cause second order messengers to be synthesized which can have a variety of effects. This is why metabotropic channels often have *slower effects* because they often use secondary messaging but can have *much longer lasting effects.* ^omiipv  A major effect of the second messengers is to activate ==kinases== (molecules that add a phosphate group in phosphorylation to other molecules which changes their activity).  Interestingly receptors can have various subtypes for the same neurotransmitter which have slightly different affects. This means drugs can be ingested to affect receptors for neurotransmitters only of a specific subtype. # Neurotransmitters ### Types of neurotransmitters ###### **Amino acid neurotransmitters:** Mainly comprised of GABA, Glutamate, and glycine. **Amine transmitters:** ==Monoamines== are types of amino acid neurotransmitters that have been modified. Acetylcholine is a big one. Monoamines are split into catecholamine and indoleamine. Catecholamines are comprised of dopamine, epinephrine, and norepinephrine. Indoleamines are comprised of serotonin, melatonin. ^970ad6 **Peptide neurotransmitters:** Made up of short chains of amino acids. **Gas neurotransmitters:** Soluble gases that diffuse between neurons to alter processes. **Excitatory and Inhibitory neurotransmitters:** I write more about neurotransmitters pathways, effects on the body, and more in my note on [[Neurotransmitters]]. ## Drugs ^85999d ###### What are Ligands in terms of drugs? As mentioned earlier ==ligands== are substances that bind to receptors to produce some marked effect as normal enzyme. Drugs are exogenous ligands in that they don't get made in the body. They can affect behavior by binding to receptors themselves or by altering the way that neurotransmitters bind to their receptors. ###### What is the difference between agonists and antagonists? ==Agonist== ligands do the same thing as the substance that normally binds at a receptor. ![[Pasted image 20220907104733.png]] However, ==antagonist== ligands block the normal receptor from doing its activity. Some antagonists are ==competitive== meaning they literally block substances from binding in their regular spot. Some ligands bind at a different site from the normal substance binding area and are thus called noncompetitive antagonists. One example is [[Autoreceptor system#^587530|caffeine]]. ![[Pasted image 20220907104720.png]] ###### How do opioids act as agonists? They bind to Ach-R receptors to activate them. ###### What is affinity and efficacy? Some ligands are much more effective at stimulating change. The degree of how well the drug binds to the receptor is called ==affinity==. The extent to which a drug activates a response when it binds to a receptor is called its ==efficacy==. ![[Pasted image 20220907104947.png]]  (stopped here) ### The Therapeutic Index The ==Therapeutic Index (TI)== is how big the difference between effective and lethal doses is. For example, caffeine has a very large Therapeutic Index because the difference between effective and lethal doses is very high.  Measuring the TI comes with finding out the ==ED50==, the dose at which half of the participants get the desired pharmacological effect and the ==LD50==, the dose at which half of subjects show symptoms of toxicity. ![[Pasted image 20220907105706.png]]  ## How does the brain regulate what comes in and out? The brains ==[[Blood-brain barrier]]== serves as a mediator between the brain and anything that is ingested. This makes it hard for many substances to enter the brain because the brain inhibits most large molecules from entering. ## How does tolerance develop? The more drugs are used in the body the more likely it is tolerance will develop. This can happen through a variety of methods. ### Metabolic tolerance Through ==metabolic tolerance== the bodies metabolic organs like the liver and stomach might become more effective at eliminating a drug from the blood stream over time leading to tolerance.  ### Functional Tolerance The body can change receptor number in response to drug usage. The body might ==down-regulate (decrease)== receptor number making it more difficult for a drug to induce the same response as before or ==up-regulate (increase)== receptor number making the body more receptive to a drug. This response or sensitization is one of the many things that fuels addiction. #### What is cross tolerance? Cross tolerance occurs when your body becomes less reactive to a drug because it interacts with the same receptor subtype of another drug that you are using too heavily. # How drugs influence synaptic transmission for behavior change? ^af24f2 Before understanding how drugs effect behavior change it's important to understand [[The problem with deducing pathology from therapeutic drugs]]. ## Presynaptic Effects ![[Pasted image 20220913163631.png]] ### Effects on transmitter production Drugs can effect how much transmitter is produced in the presynaptic cell and therefore influence how much transmitter there is to be released. One example is ==colchicine== which impairs maintenance of microtubules and blocks axonal transport. ### Effects on transmitter release Presynaptic neurons often use autoreceptors to monitor how much transmitter they have released. Drugs that influence autoreceptors can make neurons think they have released more or less transmitter than they have. #### How does Caffeine affect transmitter release? Caffeine works as an antagonist on adenosine receptors that normally inhibits transmitter release. Once it's deactivated, more catecholamines enter the post synapse which we know are very excitatory leading to it's legendary energizing effect. This is why caffeine should only be drunk at least an hour and a half after waking up. Any earlier and adenosine levels haven't gotten enough time to rise in level in the body yet. Instead, you will get a nice coffee coma in the afternoon. #### How does Botox effect transmitter release? ==Botox (Botulinum toxin)== cuts up the SNARE proteins in the axon tendrils of neurons effectively making synaptic transmission impossible because neurotransmitters can't be released into the synapse. ### Effects on transmitter clearance Drugs can effect how transmitters are cleared or re-uptaked after being released into the postsynapse. For example, they could increase the time it takes for a transmitter to clear thus making its effects last longer. ==Cocaine== causes its incredibly happy feeling effect by stopping reuptake mechanisms for dopamine prolonging its transmitter effect. ## Postsynaptic Effects ![[Pasted image 20220913163548.png]] ### Effects on transmitter receptors Drugs can act as agonists or antagonists to alter how transmitters interact in the postsynapse. ==Opiates== likes heroin and morphine are addictive because they act as antagonists at GABA receptors and inhibiting ==GABA== transmitters in the brain which send fewer inhibitory signals to [[Dopamine|dopamine]] neurons. They also lessen pain and make you feel more calm and relaxed. Another example is Nicotine which activates Ach receptors. ### Effects on cellular processes Drugs can effect modulation of gene expression, second messengers, and the production of proteins. One common example is alchohol which causes a short stimulant period followed by a longer depressant period for most people. This effect is caused because alcohol increases the amount of ==GABA-A== receptor coupled chloride channels leading to more inhibitory stimuli from GABA. A small amount of alcohol has even been shown to stimulate dopamine pathways explaining why so many people feel so good after having a couple drinks.  ### How do anti-depressants work? One class of anti-depressants, the ==MAO inhibitors==, alleviate depression by inhibiting MAOs which normally break down monoamine neurotransmitters at axon terminals.  Another class of anti-depressants, ==trycrilics==, combat depression by increasing the synaptic content of the monoamines norepinephrine and serotonin. The most common of these are Selective Serotonin Reuptake Inhibitors which work by prolonging the reuptake of serotonin in the synapse. Serotonin is known for causing feelings of relaxation and contentment.  #### What are the main anxiety reducing drugs One more class of anxiety reducing drugs are ==anxiolytics== which belong to the family of drugs called depressants that depress or reduce neural system activity.