FPT, a Novel 5‐HT7 and 5‐HT1A Partial Agonist, Treats Neuropsychiatric Symptoms Modeled in Fmr1 Knockout Mice
Abstract
Fragile X Syndrome (FXS) is the leading monogenetic cause of intellectual disabilities and autism. Seizures, severe anxiety, and sensory hypersensitivity are also common in FXS. The central serotonin system can modulate these symptoms, and certain serotonin receptors are functionally linked with proteins known to be altered in FXS, suggesting targeting them may be therapeutic for FXS. We are developing (S)‐5‐(2′‐Fluorophenyl)‐N, N‐dimethyl‐1,2,3,4‐tetrahydronaphthalen‐2‐amine (FPT), a partial agonist at both 5‐HT7 and 5‐HT1A receptors, as a treatment for FXS and autism. We previously reported that FPT corrects repetitive behaviors and enhances social interactions—core symptom domains in FXS and autism—in wild‐type (WT) mouse models. Herein, we report the results of tests assessing the efficacy of FPT to improve behavioral phenotypes in Fmr1 knockout (KO) mice, an etiologically valid genetic model of FXS. Fmr1 KO mice have seizures when exposed to a 120 dB alarm (audiogenic seizures, AGS). 73% of vehicle‐treated Fmr1 KO mice we tested had AGS (males and females, age P23–25, N=22), however, 0% of the Fmr1 KO mice pretreated with FPT (5.6 mg/kg) had AGS (N=20). This effect was very significant (PFmr1 KO mice (vehicle, N=12, FPT, N=12, PFmr1 KO (PFmr1 KO mice.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2019
- Source ID
- 10.1096/fasebj.2019.33.1_supplement.667.2
Entities
People
- Clinton E Canal
- Jessica Armstrong
- Munmun Mukherjee
- Raymond G. Booth
Organizations
- Fraxa Research Foundation
- Mercer University
- Northeastern University
- United States Department of Defense