Haematological effects of oral administration of bitopertin, a glycine transport inhibitor, in patients with non‐transfusion‐dependent β‐thalassaemia

Bitopertin is a small molecule selective inhibitor of glycine transporter 1 (GlyT1), initially developed to increase brain extracellular levels of glycine in the vicinity of neuronal N-methyl-D-aspartate receptors for the treatment of schizophrenia. GlyT1, the pharmacological target of bitopertin, is also present as a transmembrane transporter in erythroid cells1 and accounts for 50–55% of glycine uptake in human red blood cells (RBCs).2, 3 Erythroid GlyT1 inhibition by bitopertin leads to reduced intracellular glycine availability, interfering with the first step of haem synthesis, in which 5-aminolevulinate synthase catalyses the condensation reaction between glycine and succinyl-coenzyme A, forming 5-aminolevulinic acid.