Selective alkylatation of dopamine D2 and D4 receptors in rat brain by N-(p-isothiocyanatophenethyl)spiperone.
Effects of the D2-like receptor alkylating agent NIPS (N-[p-isothiocyanatophenethyl]spiperone) on dopamine receptors in rat brain were characterized by radioreceptor assays and quantitative autoradiography. NIPS alkylated D2 and D4 receptors concentration-dependently in brain sections and transfected cells. NIPS also alkylated both receptors dose-dependently in vivo, with no effect on dopamine D1-like or serotonin 5-HT2 receptors at a dose that occluded 75% of D2 and D4 receptors. Pretreatment with D2-like receptor selective antagonist haloperidol completely blocked the effects of NIPS. The findings demonstrate that NIPS selectively alkylates D2 and D4 receptors, indicating its potential utility for studies of these receptors.
Zhang
K
K
Neuropharmacology Laboratory, Mailman Research Center, McLean Division of Massachusetts General Hospital, Belmont 02478, USA. kz@mclean.harvard.edu
Tarazi
F I
FI
Kula
N S
NS
Baldessarini
R J
RJ
Neumeyer
J L
JL
D000478:Alkylation; D000818:Animals; D001345:Autoradiography; D001923:Brain Chemistry / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D008297:Male; D017072:Neostriatum / Q000737:chemistry / Q000378:metabolism; D009714:Nucleus Accumbens / Q000737:chemistry / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050638:Receptors, Dopamine D4; D011985:Receptors, Serotonin / Q000378:metabolism; D013134:Spiperone / Q000031:analogs & derivatives* / Q000494:pharmacology
D018492:Dopamine Antagonists; C493601:Drd4 protein, rat; D011804:Quinolines; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; C068824:N-(4-isothiocyanatophenethyl)spiperone; D050638:Receptors, Dopamine D4; D013134:Spiperone; C000470:EEDQ