Abstract
Background: Pridopidine, a compound in clinical trials for Huntington's disease treatment, was originally synthesized as a dopamine D2 receptor (D2R) ligand, but later found to possess higher affinity for the sigma-1 receptor (S1R). However, the putative contributions of D2R and S1R to the behavioral profile of acutely administered pridopidine have not been investigated.
Objective: The present study sought to compare the effects of acute pridopidine on wild-type vs. D2R and S1R knockout mice, at high (60 mg/kg) and low (6 mg/kg) doses.
Method: Pridopidine effects on basal and phencyclidine-induced locomotor activity was measured in the open field test. Additionally, the actions of pridopidine on prepulse inhibition was measured in animals treated with saline or phencyclidine.
Results: Whereas inhibition of spontaneous and phencyclidine-induced locomotion was readily observed at 60 mg/kg pridopidine, neither locomotor stimulation in habituated mice, nor any effects on prepulse inhibition were detected upon pridopidine treatment. Surprisingly, inhibition of spontaneous locomotion was unaffected by both D2R and S1R deletion.
Conclusion: The present results suggest the involvement of additional targets, besides D2R and S1R, in mediating locomotor inhibition by pridopidine.
Keywords: Sigma-1 receptor, dopamine receptor, knockout mice, phencyclidine, open field, prepulse inhibition.
CNS & Neurological Disorders - Drug Targets
Title:Effects of the Dopamine Stabilizer, Pridopidine, on Basal and Phencyclidine-Induced Locomotion: Role of Dopamine D2 and Sigma-1 Receptors
Volume: 17 Issue: 7
Author(s): Kristoffer Sahlholm*, Marta Valle-Leon, Jaume Taura, Victor Fernandez-Duenas and Francisco Ciruela*
Affiliation:
- Unitat de Farmacologia, Departament Patologia i Terapeutica Experimental, Facultat de Medicina i Ciencies de la Salut, IDIBELL-Universitat de Barcelona, L`Hospitalet de Llobregat, Barcelona,Spain
- Unitat de Farmacologia, Departament Patologia i Terapeutica Experimental, Facultat de Medicina i Ciencies de la Salut, IDIBELL-Universitat de Barcelona, L`Hospitalet de Llobregat, Barcelona,Spain
Keywords: Sigma-1 receptor, dopamine receptor, knockout mice, phencyclidine, open field, prepulse inhibition.
Abstract: Background: Pridopidine, a compound in clinical trials for Huntington's disease treatment, was originally synthesized as a dopamine D2 receptor (D2R) ligand, but later found to possess higher affinity for the sigma-1 receptor (S1R). However, the putative contributions of D2R and S1R to the behavioral profile of acutely administered pridopidine have not been investigated.
Objective: The present study sought to compare the effects of acute pridopidine on wild-type vs. D2R and S1R knockout mice, at high (60 mg/kg) and low (6 mg/kg) doses.
Method: Pridopidine effects on basal and phencyclidine-induced locomotor activity was measured in the open field test. Additionally, the actions of pridopidine on prepulse inhibition was measured in animals treated with saline or phencyclidine.
Results: Whereas inhibition of spontaneous and phencyclidine-induced locomotion was readily observed at 60 mg/kg pridopidine, neither locomotor stimulation in habituated mice, nor any effects on prepulse inhibition were detected upon pridopidine treatment. Surprisingly, inhibition of spontaneous locomotion was unaffected by both D2R and S1R deletion.
Conclusion: The present results suggest the involvement of additional targets, besides D2R and S1R, in mediating locomotor inhibition by pridopidine.
Export Options
About this article
Cite this article as:
Sahlholm Kristoffer *, Valle-Leon Marta , Taura Jaume , Fernandez-Duenas Victor and Ciruela Francisco *, Effects of the Dopamine Stabilizer, Pridopidine, on Basal and Phencyclidine-Induced Locomotion: Role of Dopamine D2 and Sigma-1 Receptors, CNS & Neurological Disorders - Drug Targets 2018; 17 (7) . https://dx.doi.org/10.2174/1871527317666180627103337
DOI https://dx.doi.org/10.2174/1871527317666180627103337 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Synthesis and Preliminary Biological Evaluation of New Heterocyclic Carboxamide Models
Letters in Drug Design & Discovery Alzheimer Disease: What Role for Leptin and Insulin?
Central Nervous System Agents in Medicinal Chemistry GPR40 Carboxylic Acid Receptor Family and Diabetes: A New Drug Target
Current Drug Targets The Start of a New Era for Stroke Treatment: Mechanical Thrombectomy Devices
Current Neurovascular Research A New Model for Academics Based Drug Discovery
Current Alzheimer Research Mucoadhesive Polymers for Delivery of Drugs to the Oral Cavity
Recent Patents on Drug Delivery & Formulation Evaluating Drug Safety in Children and Adolescents with Bipolar Disorder
Current Drug Safety Effect of Valerian Extract on GABRB3 Gene MRNA Expression and Sedation in BALB/C Mice
Current Bioactive Compounds Scientific Prediction and Prophetic Patenting in Drug Discovery
Recent Patents on CNS Drug Discovery (Discontinued) Cytokines as Regulators of Atherosclerosis in Murine Models
Current Drug Targets Psychosocial Factors and Diabetes Mellitus: Evidence-Based Treatment Guidelines
Current Diabetes Reviews EDITORIAL: New Psychoactive Substances (NPS), a New Global Issue: Neuropharmacological, Chemical and Toxicological Aspects
Current Neuropharmacology Microarrays in Brain Research: Data Quality and Limitations Revisited
Current Genomics Italian Association of Clinical Endocrinologists (AME) and Italian AACE Chapter Position Statement for Clinical Practice: Assessment of Response to Treatment and Follow-Up in Gastroenteropancreatic Neuroendocrine Neoplasms
Endocrine, Metabolic & Immune Disorders - Drug Targets Bipolar Affective Disorder, Epilepsy and Migraine – Does Possible Shared Pathogenesis Explain their Association?
Current Psychopharmacology Parenting Issues in Mothers with Schizophrenia
Current Women`s Health Reviews Can Increased Food Intake Improve Psychosis? A Brief Review and Hypothesis
Current Molecular Pharmacology Recent Advancement and Technological Aspects of Pulsatile Drug Delivery System - A Laconic Review
Current Drug Targets Use of human Dihydroorotate Dehydrogenase (hDHODH) Inhibitors in Autoimmune Diseases and New Perspectives in Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery A Review of Feature Extraction from ECG Signals and Classification/ Detection for Ventricular Arrhythmias
Recent Advances in Computer Science and Communications