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Olanzapine: A Potent Agonist at the hM4D(Gi) DREADD Amenable to Clinical Translation of Chemogenetics

Mikail Weston, Teresa Kaserer, Angela Wu, Alexandre Mouravlev, Jenna C Carpenter, Albert Snowball, Samuel Knauss, Melanie von Schimmelmann, Matthew J During, Gabriele Lignani, Stephanie Schorge, Deborah Young, etc.

Sci Adv. 2019 Apr 17;5(4):eaaw1567.

PMID: 31001591

Abstract:

Designer receptors exclusively activated by designer drugs (DREADDs) derived from muscarinic receptors not only are a powerful tool to test causality in basic neuroscience but also are potentially amenable to clinical translation. A major obstacle, however, is that the widely used agonist clozapine N-oxide undergoes conversion to clozapine, which penetrates the blood-brain barrier but has an unfavorable side effect profile. Perlapine has been reported to activate DREADDs at nanomolar concentrations but is not approved for use in humans by the Food and Drug Administration or the European Medicines Agency, limiting its translational potential. Here, we report that the atypical antipsychotic drug olanzapine, widely available in various formulations, is a potent agonist of the human M4 muscarinic receptor-based DREADD, facilitating clinical translation of chemogenetics to treat central nervous system diseases.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP1977113 Perlapine Perlapine 1977-11-3 Price
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