title: Asymmetric total synthesis of tetrahydroprotoberberine derivatives and evaluation of their binding affinities at dopamine receptors.
abstract: Cocaine addiction remains a serious challenge for clinical and medical research because there is no effective pharmacological treatment. l-THP, a natural product isolated from Corydalis yanhusuo W.T. Wang, is one of the most frequently used traditional herbs to treat drug addiction in China. Our laboratory first reported that its demethylated metabolites l-ICP, l-CD, and l-CP had high affinity at dopamine D1, D2, and D5 receptors. Here we report the chemical synthesis of these metabolites and other derivatives and their binding affinities at dopamine receptors. The synthesis of these bioactive metabolites will allow further in vivo study of their potential in treating cocaine addiction.
authors.affiliation: Bio-Organic and Natural Products Laboratory, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA. Electronic address: DLee@mclean.harvard.edu.
authors.forename: David Y W
authors.initials: DYW
authors.lastname: Lee
authors.affiliation: Bio-Organic and Natural Products Laboratory, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Bio-Organic and Natural Products Laboratory, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA.
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Center for Substance Abuse Research, School of Medicine, Temple University, 3420 N. Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Pharmacology and Center for Substance Abuse Research, School of Medicine, Temple University, 3420 N. Broad Street, Philadelphia, PA 19140, USA.
authors.forename: Lee-Yuan
authors.initials: LY
authors.lastname: Liu-Chen
mesh_terms: D000818:Animals; D001600:Berberine Alkaloids / Q000138:chemical synthesis* / Q000378:metabolism; D001665:Binding Sites; D006801:Humans; D011869:Radioligand Assay; D011954:Receptors, Dopamine / Q000378:metabolism*
chemical_list: D001600:Berberine Alkaloids; D011954:Receptors, Dopamine; C014845:berbine
keywords: Cocaine; Dopamine receptor; Tetrahydroprotoberberine