Amdiglurax

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Amdiglurax (INNTooltip International Nonproprietary Name), also known by its former developmental code names ALTO-100 and NSI-189 (short for "NeuralStem Inc. 189"), is a drug described as a hippocampal neurogenesis stimulant and indirect brain-derived neurotrophic factor (BDNF) modulator which is under development for the treatment of major depressive disorder (MDD), bipolar depression, and post-traumatic stress disorder (PTSD). There has also been interest in amdiglurax for possible treatment of cognitive impairment and neurodegeneration. It is taken oral. Amdiglurax's exact mechanism of action is unknown. However, it has been disclosed to act as a highly potent agonist of the TLX. On the other hand, its developer disclosed amdiglurax to act as a dual agonist and positive allosteric modulator ("ago-PAM") of the metabotropic glutamate mGlu5 receptor and attributed its antidepressant-like effects to this action. The drug is thought to work through indirectly enhancing BDNF signaling and increasing neuroplasticity and neurogenesis in the hippocampus. It dose-dependently increases hippocampal volume at sufficiently high doses in rodents. However, the drug did not significantly affect hippocampal volume at the assessed doses in humans in a clinical study. Amdiglurax is a first-in-class drug and a small molecule. As of July 2024, amdiglurax is in phase 2 clinical trials for MDD, bipolar depression, and PTSD. A phase 3 trial for MDD is being planned. Findings of the effectiveness of amdiglurax in treating MDD in phase 1 and 2 trials have been mixed, although cognitive and memory improvements have been observed. Amdiglurax is under development by Alto Neuroscience and was previously under development by Neuralstem, Inc. It has been sold online as a nootropic and antidepressant.