A long-form α-neurotoxin from cobra venom produces potent opioid-independent analgesia

查看全文 作　　者：Zhi-xin [1]CHEN;Hui-ling [1]ZHANG;Zhen-lun [1]GU;Bo-wen [1]CHEN;Rong [1]HAN;Paul F [2]REID;Laurence N [2]RAYMOND;Zheng-hong [1]QIN

机构地区：[1]Department of Pharmacology, Soochow University School of Medicine, Suzhou 215007, China;[2]ReceptoPharm, Plantation, Florida 33324,USA

出　　处：《Acta Pharmacologica Sinica》索引2006年第27卷第4期,共7页

基　　金：Project supported by an initiative fund from Soochow University,Suzhou,China and by ReceptoPharm,USA. 摘　　要：Aim:In light of the antinociceptive activity of the short-chain neurotoxin,cobrotoxin,and other acetylcholine antagonists,the antinociceptive activity andmechanisms of cobratoxin(CTX),a long-chain postsynaptic α-neurotoxin,wasinvestigated in rodent pain models.Methods:CTX was administered intraperito-neally(30,45,68 μg/kg),intra-cerebral ventricularly(4.5 μg/kg)or microinjectedinto periaqueductal gray(PAG;4.5 μg/kg).The antinociceptive action was testedusing the hot-plate and acetic acid writhing tests m mice and rats.The involve-ment of the cholinergic system and opioid system in CTX-induced analgesia wasexamined by pretreatment of animals with atropine(0.5 mg/kg,im;or 10 mg/kg,ip)or naloxone(1 and 5 mg/kg,ip).The effect of CTX on motor activity was testedusing the Animex test.Results:CTX exhibited a dose-dependent analgesic ac-tion in mice as determined by both the hot-plate and acetic acid writhing tests.The peak effect of analgesia was seen 3 h after administration.In the mouse aceticacid writhing test,the intra-cerebral ventricular administration of CTX at 4.5 μg/kg(1/12th of a systemic dose)produced marked analgesic effects.Microinjection ofCTX(4.5 μgkg)into the PAG region did not elicit an analgesic action in rats in thehot-plate test.Atropine at 0.5 mg/kg(im)and naloxone at 1 and 5 mg/kg(ip)bothfailed to block the analgesic effects of CTX,but atropine at 10 mg/kg(ip)didantagonize the analgesia mediated by CTX in the mouse acetic acid writhing test.Acetylsalicylic acid(300 mg/kg)did not enhance the analgesic effects of CTX.Atthe highest effective dose of 68 μg/kg the neurotoxin did not change the sponta-neous mobility of mice.Conclusion:CTX has analgesic effects,which are medi-ated in the central nervous system though not through the PAG.The centralcholinergic system but not opioid system appears to be involved in theantinociceptive action of CTX. 关键词：α-神经毒素眼睛蛇痛觉缺失阿托品

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A long-form α-neurotoxin from cobra venom produces potent opioid-independent analgesia

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