In vitro biochemical evidence that the psychotomimetics phencyclidine, ketamine and dizocilpine (MK-801) are inactive at cloned human and rat dopamine D2 receptors.
Dopamine potently increased calcium mobilization in Chinese hamster ovary cells expressing human dopamine D2Long receptors (CHO-D2L cells), and increased guanosine-5'-O-(3-[35S]thio)-triphosphate binding to CHO-D2L cell and rat striatal membranes. These effects of dopamine were blocked by the dopamine D2 receptor antagonist (-)raclopride. In contrast to the findings of a recent controversial study, phencyclidine, ketamine and dizocilpine (MK-801) lacked dopamine D2 receptor full agonist, partial agonist and antagonist activity in these assays, suggesting their psychotomimetic effects, and activity in rodent models of schizophrenia, are associated with N-methyl-d-aspartate receptor blockade rather than a direct interaction with dopamine D2 receptors.
Jordan
Shaun
S
Department of Neuroscience Research, Otsuka Maryland Medicinal Laboratories, 9900, Medical Center Drive, Rockville, MD 20850, USA. shaunj@otsuka.com
Chen
Ruoyan
R
Fernalld
Raymond
R
Johnson
Janelle
J
Regardie
Karen
K
Kambayashi
Junichi
J
Tadori
Yoshihiro
Y
Kitagawa
Hisashi
H
Kikuchi
Tetsuro
T
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000235:genetics; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D007649:Ketamine / Q000494:pharmacology*; D010622:Phencyclidine / Q000494:pharmacology*; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D013462:Sulfur Radioisotopes
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D013462:Sulfur Radioisotopes; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D020891:Raclopride; D007649:Ketamine; D016291:Dizocilpine Maleate; D010622:Phencyclidine; D002118:Calcium; D004298:Dopamine