Serotonin–dopamine releasing agent

Further information: serotonin releasing agent and dopamine releasing agent

A serotonin–dopamine releasing agent (SDRA) is a type of drug which induces the release of serotonin and dopamine in the body and/or brain.[3]

SDRAs are rare, as it has proven extremely difficult to dissociate dopamine and norepinephrine release.[4][5] However, in 2014, the first selective SDRAs, a series of substituted tryptamines, albeit also acting as serotonin receptor agonists, were described.[3]

A closely related type of drug is a serotonin–dopamine reuptake inhibitor (SDRI), for instance UWA-101 (α-cyclopropyl-MDMA).[6][7][8]

  1. ^ Cite error: The named reference BloughDeckerLandavazo2019 was invoked but never defined (see the help page).
  2. ^ Cite error: The named reference US20240335414A1 was invoked but never defined (see the help page).
  3. ^ a b Cite error: The named reference BloughLandavazoPartilla2014 was invoked but never defined (see the help page).
  4. ^ Rothman RB, Blough BE, Baumann MH (January 2007). "Dual dopamine/serotonin releasers as potential medications for stimulant and alcohol addictions". AAPS J. 9 (1): E1–10. doi:10.1208/aapsj0901001. PMC 2751297. PMID 17408232. Based in part on the above rationale, we sought to identify and characterize a non-amphetamine transporter substrate that would be a potent releaser of DA and 5-HT without affecting the release of NE. After an extensive evaluation of over 350 compounds, we found it virtually impossible to dissociate NE-and DA-releasing properties, perhaps because of phylogenetic similarities between NET and DAT.
  5. ^ Negus SS, Mello NK, Blough BE, Baumann MH, Rothman RB (February 2007). "Monoamine releasers with varying selectivity for dopamine/norepinephrine versus serotonin release as candidate "agonist" medications for cocaine dependence: studies in assays of cocaine discrimination and cocaine self-administration in rhesus monkeys". J Pharmacol Exp Ther. 320 (2): 627–636. doi:10.1124/jpet.106.107383. PMID 17071819. As is commonly true for existing monoamine releasers, the potency of these compounds to release norepinephrine was similar to or higher than potency to release dopamine, and compounds with exclusive selectivity for dopamine or norepinephrine release are not yet available (Rothman et al., 2001). [...] Second, the present study documented optimal effects with releasers selective for dopamine/norepinephrine versus serotonin release; however, the degree to which the dopaminergic and/or noradrenergic effects of these drugs contributes to their profiles of behavioral effects remains to be determined. Releasers with selectivity for dopamine versus both norepinephrine and serotonin would help address this issue.
  6. ^ Huot P, Fox SH, Brotchie JM (2015). "Monoamine reuptake inhibitors in Parkinson's disease". Parkinsons Dis. 2015: 609428. doi:10.1155/2015/609428. PMC 4355567. PMID 25810948.
  7. ^ Huot P, Fox SH, Brotchie JM (June 2016). "Dopamine Reuptake Inhibitors in Parkinson's Disease: A Review of Nonhuman Primate Studies and Clinical Trials". J Pharmacol Exp Ther. 357 (3): 562–569. doi:10.1124/jpet.116.232371. PMID 27190169.
  8. ^ Johnston TH, Millar Z, Huot P, Wagg K, Thiele S, Salomonczyk D, et al. (May 2012). "A novel MDMA analogue, UWA-101, that lacks psychoactivity and cytotoxicity, enhances L-DOPA benefit in parkinsonian primates". FASEB J. 26 (5): 2154–2163. doi:10.1096/fj.11-195016. PMID 22345403.
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