Preclinical profile of a dopamine D1 potentiator suggests therapeutic utility in neurological and psychiatric disorders

• Published in: Neuropharmacology Vol. 128; pp. 351 - 365
• Main Authors: Bruns, Robert F., Mitchell, Stephen N., Wafford, Keith A., Harper, Alex J., Shanks, Elaine A., Carter, Guy, O'Neill, Michael J., Murray, Tracey K., Eastwood, Brian J., Schaus, John M., Beck, James P., Hao, Junliang, Witkin, Jeffrey M., Li, Xia, Chernet, Eyassu, Katner, Jason S., Wang, Hong, Ryder, John W., Masquelin, Meghane E., Thompson, Linda K., Love, Patrick L., Maren, Deanna L., Falcone, Julie F., Menezes, Michelle M., Zhang, Linli, Yang, Charles R., Svensson, Kjell A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2018
• Subjects: Animals; Antipsychotic Agents - therapeutic use; Blinking - drug effects; Corpus Striatum - drug effects; Corpus Striatum - metabolism; D1 receptor; Disease Models, Animal; Dopamine; Dopamine Agents - therapeutic use; Eye-blink; Isoquinolines - therapeutic use; Levodopa - therapeutic use; Macaca mulatta; Male; Maze Learning - drug effects; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nervous System Diseases - drug therapy; Nervous System Diseases - metabolism; Parkinson's disease; Positive allosteric modulator; Potentiator; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Psychotic Disorders - drug therapy; Psychotic Disorders - metabolism; Receptors, Dopamine D1 - genetics; Receptors, Dopamine D1 - metabolism; Reserpine - therapeutic use; Sleep - drug effects; Wakefulness - drug effects; Ser; L-DOPA (PubChem CID 6407); tCREB; VTA; Parkinson's disease; pGluR1; tMH; DETQ (PubChem CID 117720272.); CREB; Potentiator; Positive allosteric modulator; SN; DETQ; LMA; Dopamine; D1 receptor; hD1 mouse; SCH39166 (PubChem CID 107930); GluR1; pCREB; tGluR1; tMIAA; Eye-blink; PAM; SKF 82958 (PubChem CID 1255)

DETQ, an allosteric potentiator of the dopamine D1 receptor, was tested in therapeutic models that were known to respond to D1 agonists. Because of a species difference in affinity for DETQ, all rodent experiments used transgenic mice expressing the human D1 receptor (hD1 mice). When given alone, DE...