Pharmacological aspects of R-(+)-7-OH-DPAT, a putative dopamine D3 receptor ligand.
The R-(+)-isomer of 7-hydroxy-2-(N,N-di-n-propylamino)tetralin (7-OH-DPAT) bound with a more than 200-fold higher affinity to cloned human dopamine D3 receptors (Ki = 0.57 nM) than to dopamine D2 receptors; the corresponding S-(-)-enantiomer had considerably less affinity for both dopamine receptor subtypes, indicating that the known enantiomer selectivity of 7-OH-DPAT for the 'classical' dopamine D2 receptor subtype extends to the recently discovered dopamine D3 receptor subtype. In rats R-(+)-7-OH-DPAT dose dependently (10-1000 nmol/kg) decreased dopamine release and induced yawning, while sniffing behaviour occurred at the highest dose tested (1000 nmol/kg). The possibility that the inhibition of dopamine release and the elicitation of yawning are mediated by dopamine D3 receptors is considered.
Damsma
G
G
Department of Medicinal Chemistry, University of Groningen, Netherlands.
Bottema
T
T
Westerink
B H
BH
Tepper
P G
PG
Dijkstra
D
D
Pugsley
T A
TA
MacKenzie
R G
RG
Heffner
T G
TG
Wikström
H
H
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013237:Stereoisomerism; D013764:Tetrahydronaphthalenes / Q000378:metabolism / Q000494:pharmacology*; D015000:Yawning / Q000187:drug effects
C493595:Drd3 protein, rat; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; D004298:Dopamine