Allodynia and hyperalgesia suppression by a novel analgesic in experimental neuropathic pain

SCP-1, n-[α-(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 4 h 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 Ca2+ 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.