In mouse cerebral ischemia/reperfusion injury model (2 h of transient MCAO, followed by 24 h of reperfusion) penehyclidine hydrochloride (PHC), a new cholinergic antagonist, significantly downregulates the phosphorylation of JNK, p38MAPK, and c-Jun and protects against cerebral ischemia/reperfusion injury. Here, MAPK8 is linked to brain ischemia.