Editing Neurotransmitter (section)

===Agonists===
{{Main|Agonist}}
{{expand section|coverage of full agonists and their distinction from partial agonist and inverse agonist.|date=August 2015}}
An agonist is a chemical capable of binding to a receptor, such as a neurotransmitter receptor, and initiating the same reaction typically produced by the binding of the endogenous substance.<ref>{{cite web|url=http://www.merriam-webster.com/dictionary/agonist |title=Agonist – Definition and More from the Free Merriam-Webster Dictionary |publisher=Merriam-webster.com |access-date=25 August 2014}}</ref> An agonist of a neurotransmitter will thus initiate the same receptor response as the transmitter. In neurons, an agonist drug may activate neurotransmitter receptors either directly or indirectly. Direct-binding agonists can be further characterized as [[Agonist#Types of agonists|full agonist]]s, [[partial agonist]]s, [[inverse agonist]]s.<ref>Atack J., Lavreysen H. (2010) Agonist. In: Stolerman I.P. (eds) Encyclopedia of Psychopharmacology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-68706-1_1565</ref><ref>{{cite journal|author1-link=Bryan Roth| vauthors = Roth BL | title = DREADDs for Neuroscientists | journal = Neuron | volume = 89 | issue = 4 | pages = 683–694 | date = February 2016 | pmid = 26889809 | pmc = 4759656 | doi = 10.1016/j.neuron.2016.01.040 | doi-access = free }}</ref>

[[Direct agonist]]s act similar to a neurotransmitter by binding directly to its associated receptor site(s), which may be located on the presynaptic neuron or postsynaptic neuron, or both.<ref name="Direct and indirect agonists" /> Typically, neurotransmitter receptors are located on the postsynaptic neuron, while neurotransmitter [[autoreceptor]]s are located on the presynaptic neuron, as is the case for [[monoamine neurotransmitter]]s;<ref name="Miller" /> in some cases, a neurotransmitter utilizes [[retrograde neurotransmission]], a type of feedback signaling in neurons where the neurotransmitter is released postsynaptically and binds to target receptors located on the presynaptic neuron.<ref name="Cannabinoid-Orexin systemic cross-talk" />{{#tag:ref|In the central nervous system, [[anandamide]] other [[endocannabinoid]]s utilize retrograde neurotransmission, since their release is postsynaptic, while their target receptor, [[cannabinoid receptor 1]] (CB1), is presynaptic.<ref name="Cannabinoid-Orexin systemic cross-talk">{{cite journal | vauthors = Flores A, Maldonado R, Berrendero F | title = Cannabinoid-hypocretin cross-talk in the central nervous system: what we know so far | journal = Frontiers in Neuroscience | volume = 7 | pages = 256 | date = December 2013 | pmid = 24391536 | pmc = 3868890 | doi = 10.3389/fnins.2013.00256 | doi-access = free }}<br />{{bull}}[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868890/figure/F1/ Figure 1: Schematic of brain CB1 expression and orexinergic neurons expressing OX1 or OX2]<br />{{bull}}[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868890/figure/F2/ Figure 2: Synaptic signaling mechanisms in cannabinoid and orexin systems]</ref> The [[cannabis]] plant contains [[Tetrahydrocannabinol|Δ<sup>9</sup>-tetrahydrocannabinol]], which is a direct agonist at CB1.<ref name="Cannabinoid-Orexin systemic cross-talk" />|group="note"|name="retrograde"}} [[Nicotine]], a compound found in [[tobacco]], is a direct agonist of most [[nicotinic acetylcholine receptor]]s, mainly located in [[cholinergic neuron]]s.<ref name=Fallows>{{cite web|url=http://ocw.mit.edu/ans7870/SP/SP.236/S09/lecturenotes/drugchart.htm |title=Neurotransmitters and Drugs Chart |publisher=Ocw.mit.edu |access-date=25 August 2014}}</ref> [[Opiate]]s, such as [[morphine]], [[heroin]], [[hydrocodone]], [[oxycodone]], [[codeine]], and [[methadone]], are [[mu opioid receptor|μ-opioid receptor]] agonists; this action mediates their [[euphoria]]nt and [[analgesia|pain relieving]] properties.<ref name=Fallows/>

[[Indirect agonist]]s increase the binding of neurotransmitters at their target receptors by stimulating the release or preventing the [[reuptake]] of neurotransmitters.<ref name="Direct and indirect agonists">{{cite book| vauthors = Ries RK, Fiellin DA, Miller SC |title=Principles of addiction medicine.|date=2009|publisher=Wolters Kluwer/Lippincott Williams & Wilkins|location=Philadelphia|isbn=9780781774772|pages=709–710|edition=4th|url=https://books.google.com/books?id=j6GGBud8DXcC&pg=PA709|access-date=16 August 2015}}</ref> Some indirect agonists [[releasing agent|trigger neurotransmitter release]] and [[reuptake inhibitor|prevent neurotransmitter reuptake]]. [[Amphetamine]], for example, is an indirect agonist of postsynaptic dopamine, norepinephrine, and serotonin receptors in each their respective neurons;<ref name="Miller" /><ref name="E Weihe" /> it produces both neurotransmitter release into the presynaptic neuron and subsequently the synaptic cleft and prevents their reuptake from the synaptic cleft by activating [[TAAR1]], a presynaptic [[G protein-coupled receptor]], and binding to a site on [[VMAT2]], a type of [[monoamine transporter]] located on [[synaptic vesicles]] within [[monoamine neurotransmitter|monoamine neurons]].<ref name="Miller" /><ref name="E Weihe" />