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Psychopharmacology (Berl). 2013 Jul;228(2):187-97. doi: 10.1007/s00213-013-3027-7. Epub 2013 Feb 28.

Assessment of the abuse liability of ABT-288, a novel histamine H₃ receptor antagonist.

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Department of Preclinical Safety-Development Sciences, AbbVie, Inc., 1 N. Waukegan Rd., North Chicago, IL 60064, USA.



Histamine H3 receptor antagonists, such as ABT-288, have been shown to possess cognitive-enhancing and wakefulness-promoting effects. On the surface, this might suggest that H3 antagonists possess psychomotor stimulant-like effects and, as such, may have the potential for abuse.


The aim of the present study was to further characterize whether ABT-288 possesses stimulant-like properties and whether its pharmacology gives rise to abuse liability.


The locomotor-stimulant effects of ABT-288 were measured in mice and rats, and potential development of sensitization was addressed. Drug discrimination was used to assess amphetamine-like stimulus properties, and drug self-administration was used to evaluate reinforcing effects of ABT-288. The potential development of physical dependence was also studied.


ABT-288 lacked locomotor-stimulant effects in both rats and mice. Repeated administration of ABT-288 did not result in cross-sensitization to the stimulant effects of d-amphetamine in mice, suggesting that there is little overlap in circuitries upon which the two drugs interact for motor activity. ABT-288 did not produce amphetamine-like discriminative stimulus effects in drug discrimination studies nor was it self-administered by rats trained to self-administer cocaine. There were no signs of physical dependence upon termination of repeated administration of ABT-288 for 30 days.


The sum of these preclinical data, the first of their kind applied to H3 antagonists, indicates that ABT-288 is unlikely to possess a high potential for abuse in the human population and suggests that H3 antagonists, as a class, are similar in this regard.

[Indexed for MEDLINE]

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