A dopamine D3 receptor antagonist
FAUC-365 is a D3 dopamine receptor agonist.
The dopamine D3 receptor, first identified in 1990, is preferentially expressed in the nucleus accumbens, where dopamine is released by neurons originating from the ventral tegmental area. Convincing pharmacological studies implicate D3-mediated neurotransmission in the reinforcing effects of cocaine. It is therefore a target for drugs which treat drug addiction, schizophrenia, as well as Parkinson's disease.
In vitro: FAUC-365 was discovered by a rational and interactive SAR sequence. As a dichloro derivative, FAUC-365 revealed D3 affinities that were comparable to its methoxy-substituted analogues, however, the selectivities of FAUC-365 against 5HT-1A, 5-HT2, and R1 were substantially higher, which was demonstrated by that extraordinary selectivity ratios of 17600, 7200, 5200, and 680 over D1, D2long, D2short, and D4, respectively, were determined for FAUC-365 with Ki of 0.50 nM. In addition, the benzothiophene analog FAUC 346 and its oxa analogue showed partial agonist character with EC50 values at 0.36 and 1.5 nM, respectively [1].
In vivo: Up to now, there is no animal in vivo data reported for FAUC-365.
Clinical trial: So far, no clinical study has been conducted.
Reference:
[1] Bettinetti L, Schlotter K, Hübner H, Gmeiner P.? Interactive SAR studies: rational discovery of super-potent and highly selective dopamine D3 receptor antagonists and partial agonists. J Med Chem. 2002 Oct 10;45(21):4594-7.
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