ALTO-203

ALTO-203
Clinical data
Other namesALTO203
Routes of
administration		Oral[1]
Drug classHistamine H3 receptor inverse agonist

ALTO-203 is a histamine H3 receptor inverse agonist which is under development for the treatment of major depressive disorder with anhedonia.[1][2][3][4][5] It was also under development for other psychiatric disorders and neurodegenerative disorders, but development for these indications was discontinued.[1] The drug is taken orally.[1] It has been found to increase dopamine release in the nucleus accumbens and produce antianhedonic-like effects in rodents, effects which another histamine H3 receptor inverse agonist, pitolisant, did not produce.[5] ALTO-203 is under development by Alto Neuroscience.[1][2] As of July 2025, it is in phase 2 clinical trials for major depressive disorder.[1][2] In a phase 1 trial, ALTO-203 was reported to increase subjective positive mood to a similar degree as modafinil.[6] On the other hand, the drug failed to meet its primary endpoint, a measure of mood and alertness, compared to placebo in a phase 2 trial.[7][8]

See also

References

  1. ^ a b c d e f "ALTO 203". AdisInsight. 7 July 2025. Retrieved 5 June 2026.
  2. ^ a b c "Synapse". synapse.patsnap.com.
  3. ^ Cooper N, Jordan J, Huys Q, Hajcak G, Avissar M, Powell J, et al. (December 2024). "Validation of assessments for reward processing, positive emotion, and anhedonia for use in a phase 2 study of a novel histamine H3 inverse agonist, ALTO-203, in major depression". Neuropsychopharmacology. 49: 505–506.
  4. ^ Jordan J, Shen L, Ravindran A, Sundar G, Wang C, Etkin A, et al. (January 2026). "Prospective replication of an EEG biomarker for predicting changes in attention in ALTO-203, an H3 inverse agonist". Neuropsychopharmacology. 51 (Suppl 1).
  5. ^ a b Shen L, Guo Y, Ferreira da Silva M, Ravindran AS, Wang C, Savitz AJ, et al. (2025). ALTO-203, a Novel Histamine H3 Inverse Agonist, Increase Sucrose Preference in Dopamine-depleted Rats (PDF). Society of Biological Psychiatry's 2025 Meeting.
  6. ^ Cooper NJ, Jordan JT, Huys QJ, Hajcak G, Avissar M, Powell J, et al. (2024). Effects of ALTO-203 on positive emotion and reward processing: methods and supporting data for an ongoing phase 2 proof-of-concept study (PDF). European College of Neuropsychopharmacology (ECNP) 2024.
  7. ^ Taylor NP (26 June 2025). "Alto misses primary efficacy endpoint in phase 2 depression trial". Fierce Biotech. Retrieved 5 June 2026.
  8. ^ Kuntz L (5 June 2026). "ALTO-203 Fails to Meet Primary Efficacy Endpoint in Phase 2 Major Depressive Disorder Trial". Psychiatric Times. Retrieved 5 June 2026.
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