Chemistry:Etrabamine
Etrabamine (INN; developmental code name JL-14839 or 14.839JL), also known as 6-methylamino-4,5,6,7-tetrahydrobenzothiazole, is a dopamine receptor agonist which was under development for the treatment of Parkinson's disease but was never marketed.[1][2][3][4][5] It is taken orally.[1]
The drug shows affinity for the dopamine D2 and D3 receptors (Ki = 2,620 nM and 300 nM, both for L-etrabamine).[6][7][5] It acts as a dopamine D2 and D3 receptor agonist and does not appear to act as an agonist of the dopamine D1 receptor.[5][6][7] Etrabamine produces stereotypy in rodents and to a greater extent than apomorphine.[5][7] This can be blocked by the dopamine D2 and D3 receptor antagonists sulpiride, haloperidol, and pimozide.[5] It reverses the hypolocomotion induced by the dopamine depleting agent reserpine in rodents.[5] The drug reduces levels of dopamine metabolites in the striatum in rodents.[5] It strongly suppresses prolactin levels in rodents.[5]
The chemical synthesis of etrabamine has been described.[7] The chemical structure of etrabamine was unlike that of other dopamine receptor agonists when it was first developed in the 1980s.[3][5] Subsequently, pramipexole, a closely related derivative of etrabamine, was developed and introduced for the treatment of Parkinson's disease.[4][3][6][8] Pramipexole shows 2.7- and 29-fold higher affinity for the dopamine D2 and D3 receptors than etrabamine, respectively.[6][7] Various other analogues and derivatives of etrabamine besides pramipexole have also been developed.[3][6][9]
Etrabamine was first described in the scientific literature in 1987.[3][5] It was under development by Logeais.[1][2] The drug reached phase 2 clinical trials prior to the discontinuation of its development in 1997.[1][2][4] Its close derivative pramipexole was first approved for medical use in 1997.[8]
See also
- List of investigational Parkinson's disease drugs
- Talipexole
References
- ↑ 1.0 1.1 1.2 1.3 "Etrabamine". 14 October 1997. https://adisinsight.springer.com/drugs/800003368.
- ↑ 2.0 2.1 2.2 "Delving into the Latest Updates on Etrabamine hydrochloride with Synapse". 24 January 2026. https://synapse.patsnap.com/drug/1535c5b6f50f42f8acb1630301b232f4.
- ↑ 3.0 3.1 3.2 3.3 3.4 Sasse BC (2007). Development of novel ligands influencing neurotransmission in the central nervous system (PDF) (Doctoral thesis). Frankfurt am Main: der Johann Wolfgang Goethe-Universität. Archived from the original (PDF) on 15 March 2019.
Etrabamine has been developed as a new long-lasting dopamine agonist for Parkinson's disease in the 1980's. It has been demonstrated to be more effective than the dopamine agonist apomorphine, has decreased the prolactine secretion and did not modify adenylyl cyclase activity.229
- ↑ 4.0 4.1 4.2 "G protein-coupled receptors: A golden key to the treasure-trove of neurodegenerative diseases". Clinical Nutrition 46: 155–168. March 2025. doi:10.1016/j.clnu.2025.01.032. PMID 39933302.
- ↑ 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 "Behavioural and biochemical studies on 6-methylamino-4,5,6,7-tetrahydrobenzothiazole (14.839JL), a new potent dopaminergic agonist". Pharmacological Research Communications 19 (8): 555–565. August 1987. doi:10.1016/0031-6989(87)90093-2. PMID 3432322.
- ↑ 6.0 6.1 6.2 6.3 6.4 "Talipexol als Leitstruktur zur Darstellung neuer Liganden an D2- und D3-Dopaminrezeptoren" (in de). 2018. https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=46415.
- ↑ 7.0 7.1 7.2 7.3 7.4 "Pharmaceutical compositions containing l-etrabamine, uses thereof, and methods for preparing same". 12 March 1996. https://patents.google.com/patent/WO1996028157A1/en.
- ↑ 8.0 8.1 "Classics in Chemical Neuroscience: Pramipexole". ACS Chemical Neuroscience 11 (17): 2506–2512. September 2020. doi:10.1021/acschemneuro.0c00332. PMID 32786316.
- ↑ "P3.6 Bioisosteric Replacements for Optimized Dopamine Receptor Agonists". Interdisciplinary Chemical Approaches for Neuropathology CM1103, "4th Neuroscience Day, University of Malta". 2013. pp. 112. doi:10.7423/XJENZA.2013.2.12. https://www.xjenza.org/JOURNAL/OLD/1-2-2013/12%20-%20proceedings.pdf. "Based on the early discovery of Etrabamine and established on the non-ergot dopamine agonist Pramipexole we have developed a series of tetrahydrobenzothiazole derivatives with high receptor affinity, improved receptor subtype selectivity and different efficacy profiles from agonist to antagonist properties."
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