The rate of dasotraline brain entry is slow following intravenous administration

• Published in: Psychopharmacology Vol. 237; no. 11; pp. 3435 - 3446
• Main Authors: Lew, Robert, Constantinescu, Cristian C., Holden, Daniel, Carson, Richard E., Carroll, Vincent, Galluppi, Gerald, Koblan, Kenneth S., Hopkins, Seth C.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.11.2020; Springer; Springer Nature B.V
• Subjects: 1-Naphthylamine - administration & dosage; 1-Naphthylamine - analogs & derivatives; 1-Naphthylamine - metabolism; Administration, Intravenous; Analysis; Animals; Biomedical and Life Sciences; Biomedicine; Blood-brain barrier; Brain - drug effects; Brain - metabolism; Chemical reaction, Rate of; Dopamine; Dopamine - metabolism; Dopamine D2 receptors; Dopamine Plasma Membrane Transport Proteins - antagonists & inhibitors; Dopamine Plasma Membrane Transport Proteins - metabolism; Dopamine transporter; Dopamine Uptake Inhibitors - administration & dosage; Dopamine Uptake Inhibitors - metabolism; Drug abuse; Female; Intravenous administration; Macaca mulatta; Male; Methylphenidate; Methylphenidate - administration & dosage; Methylphenidate - metabolism; Neostriatum; Neurosciences; Noradrenaline; Norepinephrine; Original Investigation; Pharmacodynamics; Pharmacology/Toxicology; Positron emission tomography; Positron-Emission Tomography - methods; Psychiatry; Raclopride; Receptors, Dopamine D2 - metabolism; Recreational drugs; United States; Dopamine; Nonhuman primate; Dopamine transporter; [; F]-FE-PE2I; PET; C]-Raclopride; [18F]-FE-PE2I; [11C]-Raclopride

Rationale Drugs that rapidly increase dopamine levels have an increased risk of abuse. Dasotraline (DAS) is a dopamine and norepinephrine reuptake inhibitor characterized by slow oral absorption with low potential for abuse. However, it remains unclear whether intravenous (i.v.) administration would...