19 Harley St, London, W1G 9QJ, UK

A-887826 is a structurally novel, potent and voltage-dependent Na(v)1.8 sodium channel blocker that attenuates neuropathic tactile allodynia in rats

Activation of sodium channels is essential to action potential generation and propagation. Recent genetic and pharmacological evidence indicates that activation of Na(v)1.8 channels contributes to chronic pain. Herein, we describe the identification of a novel series of structurally related pyridine derivatives as potent Na(v)1.8 channel blockers. A-887826 exemplifies this series and potently (IC(50)=11nM) blocked recombinant human Na(v)1.8 channels. A-887826 was approximately 3 fold less potent to block Na(v)1.2, approximately 10 fold less potent to block tetrodotoxin-sensitive sodium (TTX-S Na(+)) currents and was >30 fold less potent to block Na(V)1.5 channels. A-887826 potently blocked tetrodotoxin-resistant sodium (TTX-R Na(+)) currents (IC(50)=8nM) from small diameter rat dorsal root ganglion (DRG) neurons in a voltage-dependent fashion. A-887826 effectively suppressed evoked action potential firing when DRG neurons were held at depolarized potentials and reversibly suppressed spontaneous firing in small diameter DRG neurons from complete Freund’s adjuvant inflamed rats. Following oral administration, A-887826 significantly attenuated tactile allodynia in a rat neuropathic pain model. Further characterization of TTX-R current block in rat DRG neurons demonstrated that A-887826 (100nM) shifted the mid-point of voltage-dependent inactivation of TTX-R currents by approximately 4mV without affecting voltage-dependent activation and did not exhibit frequency-dependent inhibition. The present data demonstrate that A-887826 is a structurally novel and potent Na(v)1.8 blocker that inhibits rat DRG TTX-R currents in a voltage-, but not frequency-dependent fashion. The ability of this structurally novel Na(v)1.8 blocker to effectively reduce tactile allodynia in neuropathic rats further supports the role of Na(v)1.8 sodium channels in pathological pain states

Keywords : analogs & derivatives,Animals,Biophysics,Cells,Cultured,chemistry,Chronic Pain,complications,cytology,Disease Models,Animal,Dose-Response Relationship,Drug,drug effects,drug therapy,Electric Stimulation,etiology,Freund’s Adjuvant,Ganglia,Spinal,Humans,Hyperalgesia,Male,Membrane Potentials,metabolism,methods,Morpholines,NAV1.8 Voltage-Gated Sodium Channel,Neuralgia,Neurons,Niacinamide,Pain,Pain Threshold,Patch-Clamp Techniques,pharmacology,Rats,Rats,Sprague-Dawley,Sensory Receptor Cells,Sodium Channel Blockers,Sodium Channels,Spinal Cord Injuries,Tetrodotoxin,therapeutic use,Transfection,, Structurally,Novel,Potent, fibromyalgia specialists near me uk

Date of Publication : 2010 Sep

Authors : Zhang XF;Shieh CC;Chapman ML;Matulenko MA;Hakeem AH;Atkinson RN;Kort ME;Marron BE;Joshi S;Honore P;Faltynek CR;Krafte DS;Jarvis MF;

Organisation : Neuroscience Research, Abbott Laboratories, 100 Abbott Park Rd., Abbott Park, IL 60064, USA

Journal of Publication : Neuropharmacology

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/20566409

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

Truspilot Reviews

London Spine Unit Harley Street Hospital

A Focus on High Quality Specialised Care

We are a specialist Private Hospital based on Harley Street, London UK The Harley Street Hospital, Day Surgery Hospital

We provide exclusive health services for individuals seeking Advanced medical, non-surgical or minimally invasive treatments. We are covered by All Insurance Companies apart from AXA PPP

Our Medical Director and Lead Spinal Surgeon Mr Mo Akmal MD is a world renowned Spine Specialist Consultant with over 20 years of experience. He and his team have developed revolutionary techniques to perform all types of Spinal Surgery as a Day Case procedure without traditional General Anaesthetic.

We are constantly improving our techniques for treatment and improving facilities for our patients.

Book your Appointment Now 
Check out our Reviews 
Check out our Patient Videos 
Check our Mr Akmal’s Profile


What our patients say ...

A-887826 is a structurally novel, potent and voltage-dependent Na(v)18 sodium channel blocker that attenuates neuropathic tactile allodynia in rats | Laser spine institute london ontario

Revolutionary Keyhole surgical technique to vaporise bulging discs

Dr Mo Akmal Medical Director
Dr Mo Akmal MD - Lead Spinal Surgeon

Laser Disc Surgery can be performed under local anaesthetic at The Harley Street Hospital.

Initial Consultation

with Consultant Spine Surgeon
£ 250
  • No Waiting Times
  • Top NHS affiliated Consultant
  • Includes Clinical Review and Report
  • Multidisciplinary discussion
  • Review of Previous Scans and Reports

Follow up Consultation

any appointment after initial consultation
£ 180
  • Top NHS affiliated Consultant
  • Includes Clinical Review and Report
  • Multidisciplinary discussion

High Resolution MRI Scan

any Single Region (3.0 Tesla)
£ 600
  • No waiting times
  • Includes Full Radiologist Report
  • Open or Closed MRI scan types
  • Copy of Scan on CD

Website Offer

Pre-Booked Online
£ 800
  • Initial Consultation
  • MRI Scan (Single Region)
  • Follow Up consultation
  • Same Day One Stop Visit
  • Full Medical and MRI scan Report
  • Copy of scan on CD

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