Uhl George, Kannan Balaji, Choi Joungil, Henderson Ian, Gregory Bridget, Solon Jared, Wells Corinne, Levin Edward D
Department of Neurology, University of Maryland School of Medicine, Baltimore MD 21201.
VA Maryland Healthcare System, Baltimore MD 21201.
bioRxiv. 2025 Jul 31:2025.07.28.667221. doi: 10.1101/2025.07.28.667221.
Pentilludin is a novel, potent (690 nM) irreversible inhibitor of actions of the receptor type protein tyrosine phosphatase D (PTPRD). Pentilludin displays no 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.
喷替鲁定是一种新型、强效（690 nM）的受体型蛋白酪氨酸磷酸酶D（PTPRD）作用的不可逆抑制剂。喷替鲁定在艾姆斯试验、微核试验、人ether-à-go-go相关基因（hERG）通道或目前已获许可药物的靶点上均无活性。用高达100 mg/kg/天的喷替鲁定剂量处理大鼠两周，未发现其出现行为、血液学或血清化学异常。在每隔一天的周一-周三-周五自我给药环节之前，皮下注射20 mg/kg喷替鲁定，可显著减少苯丙胺的自我给药，并适度减少瑞芬太尼的自我给药。喷替鲁定提供了一种新型方法，可减少精神兴奋剂以及适度减少阿片类药物的自我给药，其方式可能会增强人类的戒断效果。
