L-745870 hydrochloride is a robust, selective, brain-penetrant, and orally active dopamine D4 receptor antagonist with a Ki of 0.43 nM. It exhibits weaker affinity for D2 (Ki of 960 nM) and D3 (Ki of 2300 nM) receptors, and shows moderate affinity for 5-HT2 receptors, sigma sites, and α-adrenoceptors[1][2][3].
体内研究
After oral administration to squirrel monkeys, L745870 at a dose of 10 mg/kg causes mild sedation, while more pronounced extrapyramidal motor symptoms, particularly bradykinesia, become evident at 30 mg/kg. Lower doses of L-745870 show no noticeable behavioral effects in monkeys[1].
体外研究
L-745870 effectively counteracts the D4 receptors' ability to suppress agonist-induced stimulation of [35S]-GTPgS binding; it also blocks the inhibition of forskolin-stimulated adenylate cyclase activity in transfected human embryonic kidney (HEK293) and Chinese hamster ovary (CHO) cells; prevents dopamine-induced suppression of Ca2+ currents in transfected GH4C1 pituitary cells; inhibits the activation of cloned G protein-coupled inwardly rectifying K+ channels by D4; and counters dopamine-induced increases in extracellular acidification in transfected cells[1].
L-745870 HCl 细胞实验
Cell Line
Concentration
Treated Time
Description
References
P23H rat RGCs
1μM
~10 minutes
To investigate the effects of L-745870 on the light sensitivity of P23H rat RGCs. Results showed that L-745870 increased light sensitivity but had no significant effect on the maximum peak response or dynamic range of RGCs.
PLoS One. 2015 Dec 30;10(12):e0146154
Sprague-Dawley rat RGCs
1μM
~10 minutes
To investigate the effects of L-745870 on the light sensitivity of Sprague-Dawley rat RGCs. Results showed that L-745870 decreased light sensitivity and reduced the maximum peak response of RGCs.
PLoS One. 2015 Dec 30;10(12):e0146154
L-745870 HCl 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Rats
Anesthetized rat model
Subcutaneous injection
5 and 10 mg/kg
Single injection
To investigate the effect of D4R antagonist on low-frequency oscillations in the prefrontal cortex and hippocampus. Results showed that D4R antagonist decreased delta power in the prefrontal cortex and increased theta power in the hippocampus.
Int J Mol Sci. 2022 Oct 3;23(19):11705
Male Wistar rats
Satiated rat model
Intra-NAc shell microinjection
0.1 µg
Single administration, observed for 60 minutes
To investigate the effects of D4R agonist PD-168077 and antagonist L-745870 on sweet solution intake in satiated rats. Results showed that PD-168077 significantly increased sweet solution intake (by 46%), and this effect was reversed by L-745870.
Brain Sci. 2024 Oct 30;14(11):1103
Adult male C57BL6/J mice
Intermittent binge eating model
Intraperitoneal injection
5 mg/kg
Administered 30 min before each BET, for 3 BET sessions
To evaluate the effect of DRD4 antagonist on binge-like intake, results showed that DRD4 antagonist reduced binge-like intake of PF.
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