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Psychoactive drugs operate by temporarily affecting a person's neurochemistry, which in turn causes changes in a person's mood, cognition, perception and behavior. There are many ways in which psychoactive drugs can affect the brain. Each drug has a specific action on one or more neurotransmitter or neuroreceptor in the brain. Drugs that increase activity in particular neurotransmitter systems are called agonists. They act by increasing the synthesis of one or more neurotransmitters, by reducing its reuptake from the synapses, or by mimicking the action by binding directly to the postsynaptic receptor. Drugs that reduce neurotransmitter activity are called antagonists, and operate by interfering with synthesis or blocking postsynaptic receptors so that neurotransmitters cannot bind to them.[39] Exposure to a psychoactive substance can cause changes in the structure and functioning of neurons, as the nervous system tries to re-establish the homeostasis disrupted by the presence of the drug (see also, Neuroplasticity). Exposure to antagonists for a particular neurotransmitter increases the number of receptors for that neurotransmitter, and the receptors themselves become more sensitive. This is called sensitization. Conversely, overstimulation of receptors for a particular neurotransmitter causes a decrease in both number and sensitivity of these receptors, a process called desensitization or tolerance. Sensitization and desensitization are more likely to occur with long-term exposure, although they may occur after only a single exposure. These processes are thought to underlie dependence and addiction.[40] Physical dependence on antidepressants or anxiolytics may result in worse depression or anxiety, respectively, as withdrawal symptoms. Unfortunately, because clinical depression (also called major depressive disorder) is often referred to simply as depression, antidepressants are often requested by and prescribed for patients who are depressed, but not clinically depressed. Affected neurotransmitter systems The following is a brief table of notable drugs and their primary neurotransmitter, receptor or method of action. It should be noted that many drugs act on more than one transmitter or receptor in the brain.[41] Neurotransmitter/receptor Classification Examples Acetylcholine.svg Acetylcholine Cholinergics (acetylcholine receptor agonists) arecoline, nicotine, piracetam Muscarinic antagonists (acetylcholine receptor antagonists) scopolamine, benzatropine, dimenhydrinate, diphenhydramine, atropine, quetiapine, olanzapine, most tricyclics Nicotinic antagonists (acetylcholine receptor antagonists) memantine, bupropion Adenosin.svg Adenosine Adenosine receptor antagonists[42] caffeine, theobromine, theophylline Dopamine2.svg Dopamine Dopamine reuptake inhibitors (DRIs) cocaine, amphetamine, bupropion, methylphenidate Dopamine releasers amphetamine, agomelatine Dopamine receptor agonists pramipexole, Ropinirole, L-DOPA (prodrug), memantine (also see NMDA, below) Dopamine receptor antagonists haloperidol, droperidol, many antipsychotics (e.g., risperidone, olanzapine, quetiapine) Dopamine receptor partial agonists aripiprazole Gamma-Aminobuttersäure - gamma-aminobutyric acid.svg GABA GABA reuptake inhibitors tiagabine, vigabatrin GABA receptor agonists ethanol, barbiturates, diazepam, clonazepam, lorazepam, temazepam, alprazolam and other benzodiazepines, zolpidem, eszopiclone, zaleplon and other nonbenzodiazepines, muscimol GABA receptor antagonists thujone, bicuculline Norepinephrine structure with descriptor.svg Norepinephrine Norepinephrine reuptake inhibitors most non-SSRI antidepressants such as amoxapine, atomoxetine, bupropion, venlafaxine, quetiapine, the tricyclics, methylphenidate, SNRIs such as duloxetine, venlafaxine. Norepinephrine releasers ephedrine, mianserin, mirtazapine, PPA, pseudoephedrine Norepinephrine receptor agonists clonidine, guanfacine, phenylephrine Norepinephrine receptor antagonists carvedilol, metoprolol, mianserin, prazosin, propranolol, trazodone, yohimbine, olanzapine Serotonin.svg Serotonin Serotonin receptor agonists LSD, psilocybin, mescaline, DMT Serotonin reuptake inhibitors most antidepressants including tricyclics such as imipramine, SSRIs such as fluoxetine, sertraline and citalopram, and SNRIs such as duloxetine and venlafaxine Serotonin releasers fenfluramine, MDMA (ecstasy), mephedrone, mirtazapine, tramadol Serotonin receptor antagonists ritanserin, mirtazapine, mianserin, trazodone, cyproheptadine, memantine, atypical antipsychotics (e.g., risperidone, olanzapine, quetiapine) AMPA.svg AMPA receptor AMPA receptor positive allosteric modulators aniracetam, CX717, piracetam AMPA receptor antagonists kynurenic acid, NBQX, topiramate Tetrahydrocannabinol.svg Cannabinoid receptor Cannabinoid receptor agonists THC, cannabidiol, cannabinol Cannabinoid receptor inverse agonists Rimonabant Anandamide reuptake inhibitors [43] LY 2183240, VDM 11, AM 404 FAAH enzyme inhibitors MAFP, URB597, N-Arachidonylglycine Melanocortin receptor Melanocortin receptor agonists bremelanotide NMDA receptor NMDA receptor antagonists ethanol, ketamine, PCP, DXM, Nitrous Oxide, glutamate, memantine (used for moderate to severe Alzheimers) GHB receptor GHB receptor agonists GHB, Amisulpride, T-HCA Sigma receptor Sigma-1 receptor agonists cocaine, DMT, DXM, fluvoxamine, ibogaine, opipramol, PCP Opioid receptor μ-opioid receptor agonists morphine, heroin, oxycodone, codeine μ-opioid receptor partial agonists buprenorphine μ-opioid receptor inverse agonists naloxone μ-opioid receptor antagonists naltrexone κ-opioid receptor agonists salvinorin A, butorphanol, nalbuphine, pentazocine, ibogaine[44] κ-opioid receptor antagonists buprenorphine Histamine receptor H1 histamine receptor antagonists diphenhydramine, doxylamine, mirtazapine, mianserin, quetiapine, olanzapine, meclozine, dimenhydrinate, most tricyclics Monoamine oxidase Monoamine oxidase inhibitors (MAOIs) phenelzine, iproniazid, tranylcypromine bind to MAO protein transporter amphetamine, methamphetamine Melatonin receptor Melatonin receptor agonists ramelteon Imidazoline receptor Imidazoline receptor agonists apraclonidine, clonidine, moxonidine, rilmenidine Orexin receptor Orexin receptor agonists modafinil Orexin receptor antagonists SB-334,867, SB-408,124, TCS-OX2-29 |
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