RGD Reference Report - Dopamine receptor contribution to the action of PCP, LSD and ketamine psychotomimetics. - Rat Genome Database

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Dopamine receptor contribution to the action of PCP, LSD and ketamine psychotomimetics.

Authors: Seeman, P  Ko, F  Tallerico, T 
Citation: Seeman P, etal., Mol Psychiatry. 2005 Sep;10(9):877-83.
RGD ID: 1581406
Pubmed: PMID:15852061   (View Abstract at PubMed)
DOI: DOI:10.1038/sj.mp.4001682   (Journal Full-text)

Although phencyclidine and ketamine are used to model a hypoglutamate theory of schizophrenia, their selectivity for NMDA receptors has been questioned. To determine the affinities of phencyclidine, ketamine, dizocilpine and LSD for the functional high-affinity state of the dopamine D2 receptor, D2High, their dissociation constants (Ki) were obtained on [3H]domperidone binding to human cloned dopamine D2 receptors. Phencyclidine had a high affinity for D2High with a Ki of 2.7 nM, in contrast to its low affinity for the NMDA receptor, with a Ki of 313 nM, as labeled by [3H]dizocilpine on rat striatal tissue. Ketamine also had a high affinity for D2High with a Ki of 55 nM, an affinity higher than its 3100 nM Ki for the NMDA sites. Dizocilpine had a Ki of 0.3 nM at D2High, but a Kd of 1.8 nM at the NMDA receptor. LSD had a Ki of 2 nM at D2High. Because the psychotomimetics had higher potency at D2High than at the NMDA site, the psychotomimetic action of these drugs must have a major contribution from D2 agonism. Because these drugs have a combined action on both dopamine receptors and NMDA receptors, these drugs, when given in vivo, test a combined hyperdopamine and hypoglutamate theory of psychosis.

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
dizocilpine affects bindingISODrd2 (Rattus norvegicus)1581406; 1581406Dizocilpine binds to Drd2 proteinRGD 
dizocilpine affects bindingEXP 1581406Dizocilpine binds to Drd2 proteinRGD 
ketamine affects bindingISODrd2 (Rattus norvegicus)1581406; 1581406Ketamine binds to Drd2 proteinRGD 
ketamine affects bindingEXP 1581406Ketamine binds to Drd2 proteinRGD 
lysergic acid diethylamide affects bindingISODrd2 (Rattus norvegicus)1581406; 1581406LSD binds to Drd2 proteinRGD 
lysergic acid diethylamide affects bindingEXP 1581406LSD binds to Drd2 proteinRGD 
phencyclidine affects bindingISODrd2 (Rattus norvegicus)1581406; 1581406Phencyclidine binds to Drd2 proteinRGD 
phencyclidine affects bindingEXP 1581406Phencyclidine binds to Drd2 proteinRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
heterocyclic compound binding  IPIlysergic acid diethylamide more ...1581406 RGD 
organic cyclic compound binding  IPIketamine1581406 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Drd2  (dopamine receptor D2)

Genes (Mus musculus)
Drd2  (dopamine receptor D2)

Genes (Homo sapiens)
DRD2  (dopamine receptor D2)


Additional Information