Allodynia and hyperalgesia suppression by a novel analgesic in experimental neuropathic pain.
SCP-1, n-[alpha-(benzisothiazol-3(2ho-ona,1-dioxide-2yl)-acetyl]-p-aminophenol (100 nmol), when intrathecally injected, suppressed tactile allodynia and thermal hyperalgesia in a rat neuropathic pain model. The tactile allodynia suppression lasted for at least 4h and SCP-M1 (100 nmol), the main metabolite of SCP-1, displayed similar suppression as SCP-1, but shorter latency, indicating SCP-M1 may be the bioactive component of SCP-1. Acetaminophen was less potent than SCP-1 and SCP-M1. To study mechanisms underlying SCP-1 action, we recorded voltage-gated Ca(2+) channel currents in acutely isolated dorsal root ganglion neurons using the whole-cell patch-clamp technique. SCP-1 and SCP-M1 inhibited non-L-type calcium channel currents up to 23.0+/-2.3% and 23.1+/-3.5%, respectively, at a depolarized pulse to -10 mV from a holding potential of -80 mV. Acetaminophen only induced 6.8+/-1.0% inhibition. The results suggest SCP-1 possesses anti-nociceptive activity in the rat model involving calcium channel blocking properties.
Cui
Jian-Guo
JG
Neuroscience Center of Excellence, Louisiana State University, Health Sciences Center, New Orleans, LA 70112, USA. jcui@lsuhsc.edu
Zhang
Xiong
X
Zhao
Yu-Hai
YH
Chen
Chu
C
Bazan
Nicolas
N
D000082:Acetaminophen / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy*; D008297:Male; D009437:Neuralgia / Q000188:drug therapy*; D009553:Nimodipine / Q000037:antagonists & inhibitors; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012439:Saccharin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014110:Touch
D000700:Analgesics; D002121:Calcium Channel Blockers; C118048:SCP 1; D000082:Acetaminophen; D009553:Nimodipine; D012439:Saccharin