Description
FAUC-365 is a dopamine D
3 receptor antagonist (K
i = 0.5 nM). It is selective for dopamine D
3 receptors over dopamine D
1, D
2L, D
2S, and D
4 receptors (K
is = 8.8, 3.6, 2.6, and 0.34 μM, respectively) as well as the serotonin (5-HT) receptor subtypes 5-HT
1A and 5-HT
2 (K
is = 0.36 and 2 μM, respectively). FAUC-365 (1-10 mg/kg) prevents memory impairment in the novel object recognition test in dopamine transporter knockdown (DAT-KD) mice when administered prior to object learning.
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].
References
[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.
