N-(4-pyridyl) methyl carbamate inhibits fast potassium currents in guinea pig dorsal root ganglion cells.
Axonal demyelination is a critical pathological phenomenon associated with spinal cord injury and multiple sclerosis (MS). Previous studies demonstrated that 4-Aminopyridine, a fast potassium channel blocker, enhances impulse conduction on damaged and/or demyelinated axons, allowing for functional recovery in spinal cord injuries and MS, but with severe therapeutic limitations. To continue to explore the therapeutic value of blocking fast potassium channels while circumventing the side effects of 4-AP, we have developed three novel 4-AP derivatives that enhance impulse conduction in spinal cord trauma. In the current study, we have shown that one of these three derivatives, N-(4-pyridyl) methyl carbamates (MC), significantly inhibits a fast, I(A) like potassium current in guinea pig dorsal root ganglion cells in a whole cell patch clamp configuration. This inhibition of I(A) likely plays a critical role in MC's ability to restore conduction in mechanically injured spinal cord axons and may present a viable alternative to 4-AP for individuals with spinal cord injury or MS. From this, compounds with greater efficacy and perhaps less side effects will likely emerge in the near future, which will greatly enhance the functional restoration and lessen the suffering of SCI and MS patients.
Sun
Wenjing
W
Department of Basic Medical Sciences, Center for Paralysis Research, USA.
Smith
Daniel
D
Bryn
Steven
S
Borgens
Richard
R
Shi
Riyi
R
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002219:Carbamates / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D011984:Sensory Receptor Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
D002219:Carbamates; C539465:N-(4-pyridyl)methyl carbamate; D026902:Potassium Channel Blockers; D011725:Pyridines; D015761:4-Aminopyridine