Dopamine D3/D2 Receptor Antagonist PF-4363467 Attenuates Opioid Drug-Seeking Behavior without Concomitant D2 Side Effects

• Published in: ACS chemical neuroscience Vol. 8; no. 1; pp. 165 - 177
• Main Authors: Wager, Travis T, Chappie, Thomas, Horton, David, Chandrasekaran, Ramalakshmi Y, Samas, Brian, Dunn-Sims, Elizabeth R, Hsu, Cathleen, Nawreen, Nawshaba, Vanase-Frawley, Michelle A, O’Connor, Rebecca E, Schmidt, Christopher J, Dlugolenski, Keith, Stratman, Nancy C, Majchrzak, Mark J, Kormos, Bethany L, Nguyen, David P, Sawant-Basak, Aarti, Mead, Andy N
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 18.01.2017
• Subjects: Analgesics, Opioid - adverse effects; Aniline Compounds - chemistry; Aniline Compounds - pharmacology; Animals; Cell Line, Transformed; Conditioning, Operant - drug effects; Dopamine Agents - pharmacology; Dopamine D2 Receptor Antagonists - chemistry; Dopamine D2 Receptor Antagonists - pharmacology; Dose-Response Relationship, Drug; Drug-Seeking Behavior - drug effects; Fentanyl - adverse effects; Humans; Male; Neuroblastoma - pathology; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D2 - metabolism; Receptors, Dopamine D3 - antagonists & inhibitors; Receptors, Dopamine D3 - metabolism; Self Administration; Sulfonamides - chemistry; Sulfonamides - pharmacology; drug-seeking behavior; reinstatement; Substance use dependence; dopamine D3 antagonist; opioid; cessation; drug addiction; CNS MPO; dopamine D2 antagonist; extrapyramidal symptoms; locomotor

Dopamine receptor antagonism is a compelling molecular target for the treatment of a range of psychiatric disorders, including substance use disorders. From our corporate compound file, we identified a structurally unique D3 receptor (D3R) antagonist scaffold, 1. Through a hybrid approach, we merged...