An N-butyl analog of benztropine, JHW007 [N-(n-butyl)-3α-[bis(4′-fluorophenyl)methoxy]-tropane], binds to dopamine transporters (DAT) but has reduced cocaine-like behavioral effects and antagonizes various effects of cocaine. For example, cocaine increased locomotion, whereas JHW007 [was minimally effective early but increased activity 24-hours after injection. JHW007 antagonized the locomotor-stimulant effect of cocaine. JHW007 blocked locomotor-stimulant effects of cocaine in both dopamine D2 and CB1 receptor knockout and wild-type mice, indicating a lack of involvement of these targets. Time-course data indicate that administration of JHW007 antagonized the locomotor-stimulant effects of cocaine within 10 minutes of injection, whereas occupancy at the DAT determined in vivo did not reach a maximum until 4.5 hours after injection. Overall, these findings suggest that JHW007 has cocaine antagonist effects that are deviate from its DAT occupancy.
See article at J Pharmacol Exp Ther 2014, 348:106–115.
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