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Author Notes:

Corresponding author at: Silvio O. Conte Center for Oxytocin and Social Cognition, Center for Translational Social Neuroscience, Department of Psychiatry and Behavioral Sciences, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA. asmit53@emory.edu

Subjects:

Research Funding:

This research was supported by NIH grant 1P50MH100023 to LJY. Additional funding was provided by NIH OD P51OD11132 to YNPRC.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Physical Sciences
  • Biochemistry & Molecular Biology
  • Chemistry, Medicinal
  • Chemistry, Organic
  • Pharmacology & Pharmacy
  • Chemistry
  • Oxytocin antagonist
  • Oxytocin receptor
  • PET imaging
  • Rhesus macaque
  • Cerebrospinal fluid
  • MALE PRAIRIE VOLES
  • INTRANASAL OXYTOCIN
  • NEUROHYPOPHYSEAL HORMONES
  • SOCIAL RECOGNITION
  • BRAIN
  • BEHAVIOR
  • PARTNER
  • REWARD
  • SYSTEM
  • PLASMA

An evaluation of central penetration from a peripherally administered oxytocin receptor selective antagonist in nonhuman primates

Tools:

Journal Title:

Bioorganic and Medicinal Chemistry

Volume:

Volume 25, Number 1

Publisher:

, Pages 305-315

Type of Work:

Article | Post-print: After Peer Review

Abstract:

The physiology of the oxytocin receptor has increasingly become a focus of scientific investigation due to its connection with social behavior and psychiatric disorders with impairments in social funciton. Experimental utilization of small molecule and peptide antagonists for the oxytocin receptor has played a role in deciphering these biological and social behavior connections in rodents. Described herein is the evaluation of a potent and selective oxytocin receptor antagonist, ALS-I-41, and details to consider for its use in nonhuman primate behavioral pharmacology experiments utilizing intranasal or intramuscular administration. The central nervous system penetration and rate of metabolism of ALS-I-41 was investigated via mass spectroscopy analysis of cerebrospinal fluid and plasma in the rhesus macaque after intranasal and intramuscular administration. Positron emission tomography was also utilized with [ 18 F] ALS-I-41 in a macaque to verify observed central nervous system (CNS) penetration and to further evaluate the effects of administration rate on CNS penetration of Sprague-Dawley rats in comparison to previous studies.

Copyright information:

© 2016. Published by Elsevier Ltd.

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