Binding Affinity, Selectivity, and Pharmacokinetics of the Oxytocin Receptor Antagonist L-368,899 in the Coyote ( < em > Canis latrans < /em > )

Comp Med. 2024 Feb 1;74(1):3-11. doi: 10.30802/AALAS-CM-23-000044.ABSTRACTL-368,899 is a selective small-molecule oxytocin receptor (OXTR) antagonist originally developed in the 1990s to prevent preterm labor. Although its utility for that purpose was limited, L-368,899 is now one of the most commonly used drugs in animal research for the selective blockade of neural OXTR after peripheral delivery. A growing number of rodent and primate studies have used L-368,899 to evaluate whether certain behaviors are oxytocin dependent. These studies have improved our understanding of oxytocin's function in the brains of rodents and monkeys, but very little work has been done in other mammals, and only a single paper in macaques has provided any evidence that L-368,899 can be detected in the CNS after peripheral delivery. The current study sought to extend those findings in a novel species: coyotes ( Canis latrans ). Coyotes are ubiquitous North American canids that form long-term monogamous pair-bonds. Although monogamy is rare in rodents and primates, all wild canid species studied to date exhibit social monogamy. Coyotes are therefore an excellent model organism for the study of oxytocin and social bonds. Our goal was to determine whether L-368,899 is a viable candidate for future use in behavioral studies in coyotes. We used captive coyotes at the USDA National Wildlife Research Center's Predator Research Facility to evaluate the pharmacokinetics of L-368,899 in blood and CSF during ...

Source: Comparative Medicine - March 27, 2024 Category: Zoology Authors: Sara M Freeman J Leon Catrow James Eric Cox Alexandra Turano McKenna A Rich Hillary P Ihrig Naveena Poudyal Cheng-Wei Tom Chang Eric M Gese Julie K Young Aaron L Olsen Source Type: research