Dorsal Root Ganglion Block

A-1048400 is a novel, orally active, state-dependent neuronal calcium channel blocker that produces dose-dependent antinociception without altering hemodynamic function in rats

Blockade of voltage-gated Ca(2)(+) channels on sensory nerves attenuates neurotransmitter release and membrane hyperexcitability associated with chronic pain states. Identification of small molecule Ca(2)(+) channel blockers that produce significant antinociception in the absence of deleterious hemodynamic effects has been challenging. In this report, two novel structurally related compounds, A-686085 and A-1048400, were identified that potently block N-type (IC(5)(0)=0.8 muM and 1.4 muM, respectively) and T-type (IC(5)(0)=4.6 muM and 1.2 muM, respectively) Ca(2)(+) channels in FLIPR based Ca(2)(+) flux assays. A-686085 also potently blocked L-type Ca(2)(+) channels (EC(5)(0)=0.6 muM), however, A-1048400 was much less active in blocking this channel (EC(5)(0)=28 muM). Both compounds dose-dependently reversed tactile allodynia in a model of capsaicin-induced secondary hypersensitivity with similar potencies (EC(5)(0)=300-365 ng/ml). However, A-686085 produced dose-related decreases in mean arterial pressure at antinociceptive plasma concentrations in the rat, while A-1048400 did not significantly alter hemodynamic function at supra-efficacious plasma concentrations. Electrophysiological studies demonstrated that A-1048400 blocks native N- and T-type Ca(2)(+) currents in rat dorsal root ganglion neurons (IC(5)(0)=3.0 muM and 1.6 muM, respectively) in a voltage-dependent fashion. In other experimental pain models, A-1048400 dose-dependently attenuated nociceptive, neuropathic and inflammatory pain at doses that did not alter psychomotor or hemodynamic function. The identification of A-1048400 provides further evidence that voltage-dependent inhibition of neuronal Ca(2)(+) channels coupled with pharmacological selectivity vs. L-type Ca(2)(+) channels can provide robust antinociception in the absence of deleterious effects on hemodynamic or psychomotor function

Keywords : administration & dosage,Administration,Oral,Analgesics,Animals,Calcium,Calcium Channel Blockers,chemistry,Chronic Pain,Dose-Response Relationship,Drug,drug effects,Hek293 Cells,Hemodynamics,Humans,Laboratories,Male,methods,Neurons,Pain,Pain Measurement,physiology,Piperidones,Pressure,Rats,Rats,Sprague-Dawley,secondary,, Novel,Orally,Active, list of elbow injuries

Date of Publication : 2012 Feb 1

Authors : Scott VE;Vortherms TA;Niforatos W;Swensen AM;Neelands T;Milicic I;Banfor PN;King A;Zhong C;Simler G;Zhan C;Bratcher N;Boyce-Rustay JM;Zhu CZ;Bhatia P;Doherty G;Mack H;Stewart AO;Jarvis MF;

Organisation : Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA. Victoria.E.Scott@Abbott.com

Journal of Publication : Biochem Pharmacol

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/22153861

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2022-06-10

Fabulous service Fabulous service. Mr Akmal truly cares about his patients and how he can improve their quality of life. I would recommend him to anyone with any kind of spinal issue.

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2022-06-08

Truly excellent results! I was diagnosed with lumbar stenosis after experiencing increasing pain in both legs. An MRI and consultation carried out at short notice confirmed this. Mr Akmal recommended that a spacer should be inserted in my lower back to correct the problem and release the nerves from the narrowing caused by stenosis. The operation was conducted very professionally and without pain. After the first two weeks the pain started to subside as expected. After 4 weeks I was completely back to normal. The result is exceptionally good and I feel renewed, with no pain whatsoever and a regained posture, ready to resume a normal life. I cannot recommend The London Spine Unit highly enough. They are medical magicians!

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2022-06-06

Sciatica My mother was in absolute agony for more than 3 months due to sciatica. It just came out of nowhere and took her out of action. From working full time she went straight to being bed bound and unable to carry out simplest of actions.The pain was 9/10 and she was bed bound for those three months. Multiple trips to A&E and GP and they wouldn't class it as an emergency therefore they wouldn't do anything about it other than upgrading the painkillers which did next to nothing for my mother. I couldn't bear to watch my mother sleeping on A&E bench in pain for 7 hours, just to be told by doctors that she wouldn't be kept in. I remember her joining her hands and begging the doctors to stop the pain which broke my heart. I then started doing research on google and London spine unit came up with Dr Mo AKMAL's profile and review. First meeting with Dr AKMAL was via ZOOM as my mother was bed bound. Dr AKMAL spoke to me and my mom and told us that this is nothing to worry about and that the pain would be 100% gone.Dr AKMAL assured us to visit the hospital so he could physically inspect my mother and give us the best solution. One trip to the london spine unit and Dr AKMAL advised us that the best solution would be to carry out Minimally invasive disectomy. Dr AKMAL advised that due to my mother being bed bound for a while, steroid injection might not give the result that my mother wishes. Dr AKMAL was very confident and showed us some videos from other patients who had gone through the same ordeal. The biggest thing i noticed between before and after was the smile on the patients face. Dr AKMAL was constantly assuring my mother throughout the meeting that he would take care of her pain and gave her 100% confidence that the result would be delivered.He promised her that she would be walking pain free the same day after the operation. Before the operation Dr GURUNG was consulted multiple times and he also was very helpful. Right after the surgery, as Dr AKMAL promised, my mother was walking and the biggest thing was that the pain was gone. My mother had forgotten to smile for three months and there i saw her smiling again. Dr AKMAL and Dr GURUNG gave us brilliant aftercare and informed us that just give them a ring if there was any issue. Its been several weeks now and my mother is heading towards complete recovery without any issues. The pain is completely gone and anyone who is reading this going through the same horrible sciatica pain you must come and see Dr AKMAL. Thank you Dr AKMAL and your whole team for helping my mom achieve this pain free life.

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2022-05-18

Extraordinary Care My 81 year old mother who has retired in Ghana was suffering from severe lower back pain so a local surgeon put her through discectomy with hardware (spine screws). The procedure was essentially botched, with one screw breaching her spinal canal resulting in extreme pain; unable to walk, pins and needles and numbness in the left leg. The hardware subsequently had become infected and loosened as a result. Her life after this surgery was the worse she has ever experienced in all her life. She had no doubt that she was eventually to die from the infection and pain. Fortunately, through diligent search, we found Mr Akmal and his team at The UK Spine Centre. She had a zoom consultation and with a ready MRI and CT scan, Mr Akmal knew exactly how to have her back to fitness and a better quality of life. She travelled to England on 26 March 2022 and had the surgery on 11 April 2022. It was a day-case. It lasted no more than 1 hour 30 minutes. She was on my feet within 2 hours pain free - still pain free 5 weeks on! To her this is simply a miracle ! She is grateful to Jehovah God for Mr Akmal and his team - thoroughly professional bunch at the top of their game. No one deserves to suffer the pain she experienced for two years. She seriously recommends Mr Akmal and his team for anything SPINE!

Luke O'Brien

2022-05-18

Bilateral discectomy and dynamic stabilisation for complete foot drop From the first phone call, the team at London Spine have been amazing. I had severe symptoms following an L4/L5 disc injury from playing sports and had complete foot drop. Mr Akmal and his team treated the situation incredibly sensitively, as I had risk of permanent damage. The whole process was so quick, from initial consultation to operation was about 96 hours. On the day of the operation, the nurses couldn’t have been more helpful, attentive and calming. The surgery was flawless, with absolutely zero pain from the operation following. I am now 8 weeks from a bi-lateral discectomy and dynamic stabilisation procedure and have regained full use of my leg and toes, with a complete range of motion also. Mr Akmal’s aftercare has been first class, with regular calls from his team in the 2 weeks following the surgery, to the final consultation and discharge. Thanks so much for giving me my life back

2022-05-09

Excellent treatment Mr Mo Akmal treated me very successfully for 2 torn discs in my back. I was in tremendous pain before I was referred to him. The treatment I received from him was excellent and he communicated with me very well throughout the whole process. I am eternally grateful to Mr Akmal for sorting out my back and would highly recommend him.

shahnaz Choudhury

2022-04-22

I had a massive bulging disk on my back… I had a massive bulging disk on my back compressing my nerve for three years. It caused me excruciating pain and almost left me disabled. I was on both crutches and completely homebound due to the severity of pain and mobility limitations. I had my lumber surgery two weeks ago and walked out of hospital within a few hours pain free on my right leg that was almost paralysing prior to surgery. The disk was shaved off releasing the nerve completely. Two days after surgery I had excruciating pain on my head that is unexplained as I had CT scan and MRI which were all fine. Dr Akmal has suggested it could be from the anaesthetic. I am extremely grateful to Dr Akmal and his very welcoming and cari g team. I would highly recommend his clinic as I have had excellent recovery.

MR HARVEY

2022-04-02

Thank you Mr Aklam After having a poor and very slow experiance in glasgow . I contacted Mr mo Amlam . Who is a true gentleman, great listener and paitent . We transfered my scans and treatments from glasgow to harley street . Mr Aklams p.a arranged a quick zoom to start our contact .I then went down for a meeting and examination and what should have been a spec scan .only to be told of a UK shortage . So 4 weeks later the scan took place in wellington hospital . Before I traveled back to glasgow. 5 days later I got a call to book me in to 19 harley street for a l3 and l4 debridement and stabilisation. The opp took place on 24th March. 2hours I was out walking 4 hours later . My pain in back groin and foot was all gone .thanks to Mr aklam . Top of his craft but more importantly pouts his patients first .he really wants to help you get better. Thank you so much Mr Robert harvey

Ken Carswell

2022-03-22

Amazing service and an amazing treatment! I can't thank Mr Akmal and team at the London Spine Unit enough for their help. I had a herniated disc in my back which was causing pain and restrictions. Compared to other offers of surgery (e.g. several nights in hospital), the day surgery and minimally invasive procedure were hugely appealing. I am now 3 weeks post surgery, have no pain and am recovering incredibly quickly if I compare myself to friends who have had a similar procedure. it was truly remarkable, straightforward and the team were kind, friendly and always helpful. very highly recommended!

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2022-03-17

Great service and painless procedure Great service and painless procedure. Definitely alleviated the pain

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A-1048400 is a novel, orally active, state-dependent neuronal calcium channel blocker that produces dose-dependent antinociception without altering hemodynamic function in rats | Mri in london