L-745,870 is a drug which acts as a dopamine receptor antagonist selective for the D4 subtype, and has antipsychotic effects in animal models, though it was not effective in human trials.
ChEBI: 3-[[4-(4-chlorophenyl)-1-piperazinyl]methyl]-1H-pyrrolo[2,3-b]pyridine is a member of piperazines.
A highly potent and selective D 4 dopamine receptor antagonist; L-745,870 has K i values of 0.51, 2300 and 960 nM for D 4 , D 3 and D 2 subtypes respectively and > 1000-fold selectivity over 5-HT 2 , D 1 and D 5 receptors.
L-745870 has good pharmacokinetic properties (20-60% oral bioavailability and plasma t1/2 2.1-2.8 hours) in both rat and monkey, and excellent brain penetration with high brain to plasma ratios in rat[2].
Following oral administration to squirrel monkeys, L745870 (10 mg/kg p.o.) induces mild sedation and extrapyramidal motor symptoms, notably bradykinesia, became apparent at 30 mg/kg. Lower doses of L-745870 has no observable behavioural effects in monkeys[2].
Human D4 Receptor: 4.3 nM (Ki); D2 Receptor: 960 nM (Ki); D3 Receptor: 2300 nM (Ki)
