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

• Published in: European journal of pharmacology Vol. 407; no. 1; pp. 47 - 51
• Main Authors: Wood, Martyn D, Boyfield, Izzy, Nash, David J, Jewitt, Frances R, Avenell, Kim Y, Riley, Graham J
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 27.10.2000; Elsevier
• Subjects: Animals; Azepines - pharmacology; Biological and medical sciences; BP 897; CHO Cells; Cricetinae; D3 receptor; Dopamine; Dopamine Agonists - pharmacology; Drug addictions; Humans; Medical sciences; Microphysiometry; Piperazines - pharmacology; Quinpirole - pharmacology; Radioligand binding; Receptors, Dopamine D2 - drug effects; Receptors, Dopamine D2 - physiology; Receptors, Dopamine D3; Toxicology; D3 receptor; Microphysiometry; BP 897; Dopamine; Radioligand binding; Human; Human origin; Partial agonist; Drug addiction; In vitro; Biological activity; CHO cell line; D3 Dopamine receptor; Prevention; Ester; Biological fixation; Dependence; Established cell line; Cocaine; Drug of abuse; Antagonist; Recombinant protein; Mechanism of action; Withdrawal syndrome
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(00)00732-9

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 p K 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.