Evidence for antagonist activity of the dopamine D3 receptor partial agonist, BP 897, at human dopamine D3 receptor

The dopaminergic system has long been implicated in the mechanisms of rewar d and addiction. 1-(4-(2-Naphthoylamino)butyl)-4-(2-methoxyphenyl)-1A-piper azine HCl (BP 897) has been claimed to be a selective dopamine D3 receptor partial agonist and has recently been shown to inhibit cocaine-seeking beha viour, 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 dopami ne D3 and D3 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 prop erties of BP 897 which have potential in the treatment of addiction and wit hdrawal. (C) 2000 Elsevier Science B.V. All rights reserved.