Bitopertin is a potent and noncompetitive glycine reuptake inhibitor targeting on GlyT1 (glycine transporter type 1), with IC50 value of 25nM. Bitopertin enhanced NMDA-dependent long-term potentiation at 100 nM but not at 300 nM in hippocampal CA1 pyramidal cells. It dose-dependently increased cerebrospinal fluid and striatal levels of glycine measured by microdialysis in rats. Also, it attenuated hyperlocomotion induced by the psychostimulant D-amphetamine or the NMDA receptor glycine site antagonist L-687,414 in mice. Additionally, it prevented the hyper-response to D-amphetamine challenge in rats treated chronically with phencyclidine, an NMDA receptor open-channel blocker. Bitopertin is usually used in study of schizophrenia. It can modulate both glutamatergic and dopaminergic neurotransmission in animal experiments that model aspects of schizophrenia.
作用机制
Bitopertin could competitively block [3H]ORG24598 binding sites at human GlyT1b.[1]
Bitopertin/比托派汀 细胞实验
Cell Line
Concentration
Treated Time
Description
References
CD34+ cells
10 nM
7 to 14 days
To evaluate the effect of Bitopertin on human β-thalassemic erythropoiesis, results showed increased cell viability, accelerated erythroid maturation, and reduced apoptosis.
JCI Insight. 2019 Nov 14;4(22):e130111
Bitopertin/比托派汀 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Β-thalassemia mouse model
Oral gavage
3, 10, 30 mg/kg/d
Once daily for 28 days
To evaluate the effect of Bitopertin on anemia in β-thalassemic mice, results showed increased hemoglobin, improved red cell morphology, reduced ineffective erythropoiesis, and enhanced red cell survival.
JCI Insight. 2019 Nov 14;4(22):e130111
Mice
Neuropathic pain model
Intraperitoneal injection
2 mg/kg
Single dose
Bitopertin significantly increased the reaction thresholds to mechanical and thermal stimuli without affecting motor activity or acute pain
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