Selective alkylatation of dopamine D2 and D4 receptors in rat brain by N-(p-isothiocyanatophenethyl)spiperone

• Published in: Neuroscience letters 1999-10, Vol.274 (3), p.155-158
• Main Authors: KEHONG ZHANG, TARAZI, F. I, KULA, N. S, BALDESSARINI, R. J, NEUMEYER, J. L
• Format: Article
• Language: English
• Subjects: Alkylation; Animals; Autoradiography; Biological and medical sciences; Brain Chemistry - drug effects; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Dopamine Antagonists - pharmacology; Fundamental and applied biological sciences. Psychology; Male; Neostriatum - chemistry; Neostriatum - metabolism; Nucleus Accumbens - chemistry; Nucleus Accumbens - metabolism; Quinolines - pharmacology; Radioligand Assay; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D2 - metabolism; Receptors, Dopamine D4; Receptors, Serotonin - metabolism; Spiperone - analogs & derivatives; Spiperone - pharmacology; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(99)00700-4

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.