Add like
Add dislike
Add to saved papers

Preclinical Reproductive and Developmental Toxicity Profile of a Glycine Transporter Type 1 (Glyt1) Inhibitor.

Bitopertin is a glycine type 1 (GlyT1) inhibitor intended for the treatment of psychiatric disorders. The principle adverse effect in the regulatory reproductive toxicity studies was peri-natal pup death when rat dams were treated during parturition at a dose resulting in five-times the human therapeutic exposure (AUC). Cessation of dosing two days before parturition prevented the pup deaths. Investigatory experiments and pharmacokinetic modelling suggested that the neonatal mortality was related to transplacental passage of bitopertin leading to high systemic levels in the newborn pups. Brain levels of bitopertin in the rat fetus and neonate were two-fold higher than in the mother. As illustrated by knock-out mice models, GlyT1 function is essential for neonatal pup survival in rodents, but is not necessary for normal prenatal morphological development. The glycine transport systems are immature at birth in the rat, but are functionally well-developed in the human newborn. While the relevance to humans of the neonatal mortality seen in rats following late gestational exposure is unknown, bitopertin would not be recommended for use during late pregnancy unless the anticipated benefit for the mother outweighs the potential risk to the newborn.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app