19 Harley St, London, W1G 9QJ, UK

Involvement of voltage-gated sodium channels blockade in the analgesic effects of orphenadrine

Orphenadrine is a drug acting on multiple targets, including muscarinic, histaminic, and NMDA receptors. It is used in the treatment of Parkinson’s disease and in musculoskeletal disorders. It is also used as an analgesic, although its mechanism of action is still unknown. Both physiological and pharmacological results have demonstrated a critical role for voltage-gated sodium channels in many types of chronic pain syndromes. We tested the hypothesis that orphenadrine may block voltage-gated sodium channels. By using patch-clamp experiments, we evaluated the effects of the drug on whole-cell sodium currents in HEK293 cells expressing the skeletal muscle (Nav1.4), cardiac (Nav1.5) and neuronal (Nav1.1 and Nav1.7) subtypes of human sodium channels, as well as on whole-cell tetrodotoxin (TTX)-resistant sodium currents likely conducted by Nav1.8 and Nav1.9 channel subtypes in primary culture of rat DRG sensory neurons. The results indicate that orphenadrine inhibits sodium channels in a concentration-, voltage- and frequency-dependent manner. By using site-directed mutagenesis, we further show that orphenadrine binds to the same receptor as the local anesthetics. Orphenadrine affinities for resting and inactivated sodium channels were higher compared to those of known sodium channels blockers, such as mexiletine and flecainide. Low, clinically relevant orphenadrine concentration produces a significant block of Nav1.7, Nav1.8, and Nav1.9 channels, which are critical for experiencing pain sensations, indicating a role for sodium channel blockade in the clinical efficacy of orphenadrine as analgesic compound. On the other hand, block of Nav1.1 and Nav1.5 may contribute to the proconvulsive and proarrhythmic adverse reactions, especially observed during overdose

Keywords : administration & dosage,Analgesics,Animals,Cells,Cultured,Chronic Pain,cytology,Dose-Response Relationship,Drug,drug effects,Ganglia,Spinal,Hand,Hek293 Cells,Ion Channel Gating,Italy,Male,Membrane Potentials,Neurons,Orphenadrine,Pain,physiology,Rats,Rats,Sprague-Dawley,Sensation,Sodium Channels,Syndrome,Tetrodotoxin,, Voltagegated,Sodium,Channels,Blockade, piriformis injection success

Date of Publication : 2009 Apr

Authors : Desaphy JF;Dipalma A;De BM;Costanza T;Gaudioso C;Delmas P;George AL;Camerino DC;

Organisation : Sezione di Farmacologia, Dipartimento FarmacoBiologico, Facolta di Farmacia, Universita di Bari, Bari, Italy. jfdesaphy@farmbiol.uniba.it

Journal of Publication : Pain

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/19217209

The London Spine Unit : Harley Street UK. Specialists in Cutting Edge Technologies for Spinal Surgery

Make an Appointment 

Trustpilot Reviews
Doctify Reviews
Top Doctor Reviews

Involvement of voltage-gated sodium channels blockade in the analgesic effects of orphenadrine | Spine zones

What our patients say ...

Consultant Spine Surgeon
Consultant Spine Surgeon
Consultant Spine Surgeon

This surgical technique consists of a percutaneous approach for the treatment of small to medium size hernias of the intervertebral disc by laser energy. The main objective is to reduce the intradiscal pressure in the nucleus pulposus

Laser Disc Surgery can be performed under local anaesthetic as a day case at our centre on the prestigious Harley Street.
What is London spine unit and How it Works

The London Spine Unit was established in 2005 and has successfully treated over 5000 patients. All conditions are treated.

treatment of all spinal disorders

The London Spine Unit specialises in Minimally Invasive Treatments allowing rapid recovery and return to normal function

Trusted by patients worldwide

The London Spine Unit provides the highest quality care to all patients and has VIP services for those seeking exceptional services

If you have any emergency Doctor’s need, simply call our 24 hour emergency

Your personal case manager will ensure that you receive the best possible care.

Call Now 

+44 844 589 2020
+44 203 973 8810