NLX-112, a highly selective 5-HT1A receptor agonist: Effects on body temperature and plasma corticosterone levels in rats

A. Newman-Tancredi, R. Depoortère, E. Carilla-Durand, J. P. Tarayre, M. Kleven, W. Koek, L. Bardin, M. A. Varney

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

NLX-112 (a.k.a. F13640 or befiradol), exhibits nanomolar affinity, exceptional selectivity and high agonist efficacy at 5-hydroxytryptamine 5-HT1A receptors. It possesses marked activity in a variety of animal models of depression, pain and L-DOPA-induced dyskinesia. However, its influence on translational biomarkers of central 5-HT1A receptor activation has not been previously described. Here, we report on the activity, in rats, of NLX-112 to increase plasma corticosterone levels and produce hypothermia, two responses which are also elicited by 5-HT1A receptor agonists in humans. NLX-112 elicited dose-dependent hypothermia (minimal effective dose, MED: 0.31 mg/kg p.o.) and also increased plasma corticosterone both by oral and intraperitoneal routes (MED: 0.63 mg/kg in both cases). The increase in corticosterone induced by NLX-112 (0.63 mg/kg p.o.) was abolished by co-administration of the selective 5-HT1A receptor antagonist, WAY100635. Additionally, NLX-112 also dose-dependently induced flat body posture, forepaw treading and lower lip retraction (MEDs 0.31–0.63 mg/kg p.o.). The doses of NLX-112 which induce hypothermia or corticosterone release were similar to those inducing serotonergic behaviors but greater than those reported previously in models of therapeutic-like activity (range 0.04 to 0.16 mg/kg). Overall, the present study provides information for clinical dose estimations of NLX-112 and suggests that therapeutic effects may occur at doses below those at which biomarker responses are observed.

Original languageEnglish (US)
Pages (from-to)56-62
Number of pages7
JournalPharmacology Biochemistry and Behavior
Volume165
DOIs
StatePublished - Feb 2018
Externally publishedYes

Keywords

  • 5-HT receptors
  • Befiradol
  • Biomarker
  • Corticosterone
  • Hypothermia
  • Serotonin

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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