title: Evidence for antagonist activity of the dopamine D3 receptor partial agonist, BP 897, at human dopamine D3 receptor.
abstract: The dopaminergic system has long been implicated in the mechanisms of reward and addiction. 1-(4-(2-Naphthoylamino)butyl)-4-(2-methoxyphenyl)-1A-piperazine HCl (BP 897) has been claimed to be a selective dopamine D3 receptor partial agonist and has recently been shown to inhibit cocaine-seeking behaviour, suggesting a role for dopamine D3 receptor agonists in the treatment of addiction. We have previously characterised the pharmacological profile of the human dopamine D3 and D2(long) receptors using microphysiometry and radioligand binding and we have now studied the interaction of BP 897 with the dopamine D2 and D3 receptors using these methods. At both human dopamine D3 and D2 receptors, BP 897 lacked agonist activity but was a potent and selective antagonist with pK(b) values of 8.05+/-0.16 (4) and 9.43+/-0.22 (4) at human dopamine D2 and D3 receptors, respectively. These results, therefore, suggest that it may be the dopamine D3 receptor antagonist properties of BP 897 which have potential in the treatment of addiction and withdrawal.
authors.affiliation: Department of Neuroscience Research, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Third Avenue, Essex, CM19 5AW, Harlow, UK. martyn_wood-1@sbphrd.com
authors.forename: M D
authors.initials: MD
authors.lastname: Wood
authors.forename: I
authors.initials: I
authors.lastname: Boyfield
authors.forename: D J
authors.initials: DJ
authors.lastname: Nash
authors.forename: F R
authors.initials: FR
authors.lastname: Jewitt
authors.forename: K Y
authors.initials: KY
authors.lastname: Avenell
authors.forename: G J
authors.initials: GJ
authors.lastname: Riley
mesh_terms: D000818:Animals; D001381:Azepines / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D018491:Dopamine Agonists / Q000494:pharmacology*; D006801:Humans; D010879:Piperazines / Q000494:pharmacology*; D019257:Quinpirole / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000502:physiology; D050637:Receptors, Dopamine D3
chemical_list: D001381:Azepines; C493593:DRD3 protein, human; D018491:Dopamine Agonists; D010879:Piperazines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D019257:Quinpirole; C120565:BP 897; C024763:talipexole