A dopamine releasing agent (DRA) is a type of drug which induces the release of dopamine in the body and/or brain. No selective DRAs are currently known. Many releasing agents of both dopamine and norepinephrine (norepinephrine–dopamine releasing agents, or NDRAs) and of serotonin, norepinephrine, and dopamine are known (serotonin-norepinephrine-dopamine releasing agents, or SNDRAs), however. Serotonin–dopamine releasing agents are much rarer and are not selective for monoamine release. Examples of NDRAs include amphetamine and methamphetamine, and an example of an SNDRA is MDMA. The most selective dopamine releaser is 4-methylaminorex, but it also has considerable activity as a norepinephrine releaser. These drugs are frequently used for recreational purposes and encountered as drugs of abuse.
A closely related type of drug is a dopamine reuptake inhibitor (DRI). Various selective DRIs are known, in contrast to the case of DRAs. It is particularly of note that the mechanism of action at the dopamine transporter (DAT) for dopamine releasers/substrates is entropy-driven (i.e. hydrophobic), whereas for dopamine re-uptake inhibitors it is enthalpy-driven (i.e. conformational change).[1][2]
There is some, albeit mixed, in vitro evidence that the antidepressant and modestly selective DRI amineptine may in addition to inhibiting the reuptake of dopamine selectively induce the presynaptic release of dopamine without affecting that of norepinephrine or serotonin.[3][4][5]
^Chemistry, Design, and Structure-Activity Relationship of Cocaine Antagonists. Satendra Singh et al. Chem. Rev. 2000, 100. 925-1024. PubMed; Chemical Reviews (Impact Factor: 45.66). 04/2000; 100(3):925-1024 American Chemical Society; 2000 ISSN 0009-2665 ChemInform; May, 16th 2000, Volume 31, Issue 20, doi:10.1002/chin.200020238. Page 928 (4th of article) 1st paragraph. Lines 8—11. Mirror hotlink.
^Bonnet JJ, Benmansour S, Costentin J, Parker EM, Cubeddu LX (June 1990). "Thermodynamic analyses of the binding of substrates and uptake inhibitors on the neuronal carrier of dopamine labeled with [3H]GBR 12783 or [3H]mazindol". The Journal of Pharmacology and Experimental Therapeutics. 253 (3): 1206–14. PMID 2141637.
^J. K. Aronson (2009). Meyler's Side Effects of Psychiatric Drugs. Elsevier. pp. 29–. ISBN 978-0-444-53266-4.
^Ceci A, Garattini S, Gobbi M, Mennini T (1986). "Effect of long term amineptine treatment on pre- and postsynaptic mechanisms in rat brain". British Journal of Pharmacology. 88 (1): 269–275. doi:10.1111/j.1476-5381.1986.tb09495.x. ISSN 0007-1188. PMC 1917102. PMID 3708219.
^Bonnet JJ, Chagraoui A, Protais P, Costentin J (1987). "Interactions of amineptine with the neuronal dopamine uptake system: Neurochemicalin vitro and in vivo studies". Journal of Neural Transmission. 69 (3–4): 211–220. doi:10.1007/BF01244342. ISSN 0300-9564. PMID 3625193. S2CID 9886698.
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