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The development of more potent GlyT1 inhibitors was initially inspired by structural modifications of sarcosine, particularly through the introduction of bulky hydrophobic substituents at the nitrogen atom, an approach guided by emerging structural and pharmacological insights into GlyT1 and its relationship to other members of the SLC6 transporter family

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Standard titration protocol from clinical trials The Phase 2 NEJM trial used the following escalation schedule for the 12 mg dose group: Weeks 1 through 4: 2 mg once weekly (subcutaneous) Weeks 5 through 8: 4 mg once weekly Weeks 9 through 12: 8 mg once weekly Week 13 and beyond: 12 mg once weekly (maintenance dose) For the 8 mg target dose, the schedule was: Weeks 1 through 4: 2 mg once weekly Weeks 5 through 8: 4 mg once weekly Week 9 and beyond: 8 mg once weekly (maintenance dose) These titration schedules are not suggestions