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bioRxiv · 10.1101/2025.07.28.667221

Pentilludin reduces rat amphetamine and remifentail self-administration with good pharmacologic and toxicologic profiles

Uhl, G.·Kannan, B.·Choi, J.·Henderson, I.·Gregory, B.·Solon, J.·Wells, C.·Levin, E.
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Abstract

Pentilludin is a novel, potent (690 nM) irreversible inhibitor of actions of the receptor type protein tyrosine phosphatase D (PTPRD). Pentilludin displays no in vitro activities in Ames or micronucleus tests, at hERG channels or at targets for currently-licensed drugs. Rats treated with pentilludin doses up to 100 mg/kg/day for two weeks have not been found to display behavioral, hematologic or serum chemistry abnormalities. Treatment with 20 mg/kg sc pentilludin prior to every other M-W-F self-administration session substantially reduces self-administration of amphetamine and more modestly reduces self-administration of remifentanil. Pentilludin provides a novel means for reducing self-administration of psychostimulant and, modestly, opiate drugs in ways that could enhance abstinence in humans.

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Uhl, G., Kannan, B., Choi, J., Henderson, I., Gregory, B., Solon, J., Wells, C., Levin, E.. 2025-08-02. Pentilludin reduces rat amphetamine and remifentail self-administration with good pharmacologic and toxicologic profiles. https://doi.org/10.1101/2025.07.28.667221

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