1-Boc-Piperidine-4-Carboxaldehyde Prevents Binge-Eating Behaviour and Anxiety in Rats

Pharmacology. 2021;106(5-6):305-315. doi: 10.1159/000513376. Epub 2021 Mar 23.

Abstract

Background: Piperidines are biogenic amines studied mainly in toxicology because they were initially found as alkaloids from peppers and insect venoms. Piperidines are also produced in the human body, and their actions seem to be related to wakefulness/sleep and other cognitive phenomena. Piperidines have been minimally characterized for therapeutic applications. In this context, 1-Boc-piperidine-4-carboxaldehyde (1-Boc-piperidine) is a piperidine-derivative molecule with no mechanism of action reported, although its uses include the synthesis of GPR119 selective agonists that have been patented as anti-obesity drugs.

Objectives: The aim of this work was to study the effects of 1-Boc-piperidine on binge-eating behaviour and anxiety in Wistar rats.

Methods: In experimental protocol 1, binge-eating behaviour was induced in animals that received pre-treatment (i.p.) with (i) vehicle (methanol 10%; 1 mL/kg), (ii) 1-Boc-piperidine (1 µmol kg-1), or (iii) 1-Boc-piperidine (10 µmol kg-1). In experimental protocol 2, mildly stressed animals were evaluated in the elevated plus maze under the acute effects of the pre-treatments applied in experimental protocol 1.

Results and conclusions: 1-Boc-piperidine decreased, in a dose-dependent manner, the intake of calories from a succulent hyper-caloric food in a binge-eating protocol in female rats, whereas the acute exposition to this piperidine exerted an anxiolytic effect in the male rat. In both effects, the mechanism of action remains to be characterized.

Keywords: 1-Boc-piperidine-4-carboxaldehyde; Anxiety; Binge-eating behaviour; GPCRs; Molecular modelling; Piperidine derivatives.

MeSH terms

  • Animals
  • Anxiety / drug therapy*
  • Anxiety / etiology
  • Behavior, Animal / drug effects
  • Binge-Eating Disorder / drug therapy*
  • Binge-Eating Disorder / etiology
  • Dose-Response Relationship, Drug
  • Energy Intake / drug effects
  • Feeding Behavior / drug effects
  • Injections, Intraperitoneal
  • Ligands
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Pain / complications
  • Protein Binding
  • Rats
  • Rats, Wistar
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Serotonin / chemistry
  • Receptors, Serotonin / metabolism
  • Stress, Psychological / complications
  • Weight Gain / drug effects

Substances

  • GPR119 protein, rat
  • Ligands
  • Receptors, G-Protein-Coupled
  • Receptors, Serotonin
  • serotonin 6 receptor
  • serotonin 7 receptor