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• W2097057470 abstract "Previous studies demonstrated that analogs of benztropine (BZT) possess high affinity for the dopamine (DA) transporter (DAT) but generally have behavioral effects different from those of cocaine, suggesting either unique actions at the DA transporter or that another action of these drugs interferes with cocaine-like effects. Because the parent compound has histamine-antagonistic effects, the affinity of its analogs for histamine H₁, H₂, and H₃ receptors were compared with DA transporter affinity to assess whether those differences predicted the amount of cocaine-like activity. All of the compounds displaced [³H]mepyramine from H₁, [¹²⁵I]iodoaminopotentidine from H₂, and [³H]<i>N</i>-α-methylhistamine from H₃ histamine receptors with affinities ranging from 15.7 to 37,600, 218 to >4430, and 4040 to >150,000 nM, respectively. Affinities at histamine H₁ receptors were, respectively, approximately 25- or 300-fold greater than those at H₂ or H₃ histamine receptors. Relative affinities for H₁ and DAT binding did not reliably predict the degree of cocaine-like stimulation of locomotor activity. In addition, interactions of various histaminic agents with cocaine assessed whether an action at any of the histamine sites could interfere with cocaine-like effects. None of the histaminic agents fully substituted for cocaine in rats trained to discriminate 10 mg/kg cocaine from saline nor did any of the compounds antagonize or otherwise diminish the discriminative stimulus effects of cocaine. The results suggest that affinity for histamine receptors cannot account for the diminished cocaine-like effects of the BZT analogs and suggest alternatively that these compounds have actions different from those of cocaine but likely mediated by their interaction with the DAT." @default.
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• W2097057470 date "2005-07-29" @default.
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• W2097057470 title "Assessment of the Influence of Histaminergic Actions on Cocaine-Like Effects of 3α-Diphenylmethoxytropane Analogs" @default.
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• W2097057470 doi "https://doi.org/10.1124/jpet.105.090829" @default.
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