The D3R partial agonist, BP 897, attenuates the discriminative stimulus effects of cocaine and D-amphetamine and is not self-administered.
Growing attention has been directed towards the potential involvement of the dopamine D3 receptor (D3R) in modulating effects of psychomotor stimulants. BP 897 (N-[4-[4-(2-methoxyphenyl)-1-piperazinyl]butyl]-2-naphthylcarboxamide; aka BP 4.897 and DO897) is amongst the most selective partial agonists for the D3R receptor thus far reported. BP 897 was tested for its ability to support self-administration in rhesus monkeys (0.3-30 microg/kg) and for its ability to produce cocaine- and D-amphetamine-like discriminative stimulus effects in mice (0.01-17 mg/kg i.p.). BP 897 was not self-administered above vehicle and saline levels in any of the four monkeys tested, and produced less than 30% generalization from either the cocaine or D-amphetamine stimulus. When BP 897 was administered before administrations of cocaine or D-amphetamine, percent drug-lever selections were reduced. These results suggest that BP 897 has a profile of activity suitable for consideration as a potential treatment for cocaine dependency disorders.
Department of Pharmacology, Virginia Commonwealth University, Medical College of Virginia, Richmond 23298-0613, USA. pbeardsl@hsc.vcu.edu
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D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003216:Conditioning, Operant; D003913:Dextroamphetamine / Q000494:pharmacology*; D004192:Discrimination, Psychological / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005793:Generalization, Psychological; D008253:Macaca mulatta; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050637:Receptors, Dopamine D3; D012646:Self Administration; D019966:Substance-Related Disorders / Q000523:psychology*
D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C120565:BP 897; D003042:Cocaine; D003913:Dextroamphetamine