Tiger Analgesic Peptide (hwap-i), Efficacy, Toxicology Studies

Huwena analgesic peptide-I (HWAP-I) is a N-type calcium ion channel blocker. The previous work in our lab indicated that it had analgesia activity. To further investigate its analgesia effect, we established several different kinds of animal models by administration through epidural space, and evaluated its toxity:I. The study of the effcts of epdural administration of HWAP-I on allodynia in rats with the model of bee venom. Using the Yon Frey hair mechanical stimulate method to observe the analgesia effects of different doses of HWAP-I on 30 minutes; 60 minutes after the administration, we found that the HWAP-I blocked the established mechanical allodynia from the dose of 0. 1 g/kg in the bee venom injured hindpaw in a plus dose-dependent manner compared with the pure saline and SNX-III, and from the dose-effect curve we found that the ED50 of 30 minutes after the administration is 23 g/kg;and the analgesia effect of 25ug/kg SNX-III is better than the same dose of HWAP-I. The result of this study show that administering epdural HWAP-I can allay the rat's chronic inflammatory pain due to the subcutanous administration of bee venom.II. The study of, the effects of epdural administration of huwena analgesic peptide-I (HWAP-I) in the rat model of chronic neuropathic pain. To compare and contrast antinociceptive properties of HWAP-I, ziconotide(SNX-III) and morphine, using the light-radiate-heat method and mechanical stimulate method and comparing the analgesia effects of 30 minutes; 60 minutes; 120minutes after the administration of different dose of them. We found that the HWAP-I blocked the established heat hyperalgesia and mechanical allodynia in the injured hindpaw. Injection of 20 g/kg HWAP-I produced long-lasting(>2h) distinct blockade of established heat hyperalgesia and mechanical allodynia. Injection of 40 g/kg morphine produced immediate and short-lasting blockade effect and had effect on bilateral. The result of this study show that administering epdural HWAP-I can allay the rat's cuff-induced neuropathic pain. III.The long-term toxicity experiment of huwena analgesic pep tide-I (HWAP-I) in the beagle dogs. The experiment is carried out by epdural administration of huwena analgesic peptide-I(HWAP-I) in the beagle dogs, which are divided in 5 groups: the pure saline group; the low-dose group; the middle-dose group; the high-dose group and the hyperhigh-dose group, Those doses which are conversed from the rat's doses are: 7. 4 g/kg , 14. 8 g/kg, 29. 7 g/kg and 59. 3 g/kg, There are 6 dogs in each group, Half of them are killed immediately to do blood analysis and pathological tests after stopping administration for 3 months, and the other half of them are killed to do the same things after stopping administration for another 14 days, and all the results show that all kinds of tissuses and organs in the beagle dogs which are administered HWAP-I by epdural for 3 months have no extinct toxicity side reaction.