UPDATE ON SCHIZOPHRENIA: NEW TREATMENTS AND …
UPDATE ON SCHIZOPHRENIA: NEW
TREATMENTS AND NOVEL TARGETS
Learning Objectives
? Review clinical advances in our understanding of
schizophrenia
? Update knowledge on novel treatments for
schizophrenia
Novel Pharmacological
Treatment for
Ameliorating Adverse
Events
Olanzapine/Samidorphan
? Samidorphan (SAM) is an opioid antagonist at the ?opioid receptor, with significant activity at k-opioid
receptors
? By blocking opioid receptors involved in the brain reward
pathway, reinforcement is reduced
? Shows similar efficacy to naltrexone but with reduced side
effects
? Investigated for addiction treatment (e.g., alcohol, cocaine)
? Co-administration of olanzapine and SAM, but not
naltrexone, mitigated olanzapine-induced weight gain,
suggesting that the added k-opioid receptor properties
may be clinically relevant
Silverman BL et al. Schizophr Res 2018;195:245-51.
Receptor Ki (nM)
?
0.052
k
0.28
2.6
Proposed Mechanism: Brain Reward Pathway
Ventral Tegmental
Area
Nucleus Accumbens
GABA
Dopamine
-endorphin pathways from
the arcuate nucleus
Samidorphan
Krogmann A et al. CNS Spectr 2019;24(S1):38-69;
Peckham AM et al. Ment Health Clin 2018;8(4):175-83;
Kenny PJ. Neuron 2011;69(4):664-79.
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