Evaluation of antinociception, tolerance and withdrawal abstinence of opioid receptor triple agonist KUST201 in rats
10.3969/j.issn.1001-1978.2016.05.012
- VernacularTitle:阿片受体三重激动剂KUST201的大鼠镇痛、耐受与戒断反应研究
- Author:
Jiuling LI
;
Qinghong KONG
;
Jie YU
;
Shoupu YI
;
Yamin LI
;
Guanlin WANG
;
Yuehai SHEN
;
Kwenjen CHANG
- Publication Type:Journal Article
- Keywords:
KUST201;
DPI-125;
antinociception;
tol-erance;
withdrawal abstinence;
opioid receptor triple agonist
- From:
Chinese Pharmacological Bulletin
2016;32(5):652-657,658
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the antinociception, tolerance and withdrawal abstinence of δ/μ/κ opioid receptor triple agonist KUST201 ( DPI-125 ) in rats. Methods Male Sprague-Dawley rats were used to de-termine the time course of analgesic effects and ED50 effects of co-administration of naltrindole were assessed as well. In withdrawal experiments, KUST201 was ad-ministrated twice daily for 3 d with increasing doses each day. On the 4th day, the rats were given a single dose, challenged with naloxone 3 h later, and signs of abstinence were monitored. Results The ED50 values of KUST201 were 0. 34 mg·kg-1 in tail-pinch test and 0. 68 mg · kg-1 in hot-plate test. The antinociception actions of KUST201 started to decrease 1 h after ad-ministration, and disappeared after 2 h. In chronic tol-erance experiments, the antinociception actions started to decrease on d 3 , and completely disappeared on d 7 . Naltrindole could reduce the antinociceptive action of KUST201. In withdrawal experiments, abstinence scores increased significantly in the dose range between 2~8 times of tail-pinch ED50 . Conclusion Compared with previously reported δ/μ/κ triple agonist DPI-3290 , KUST201 exhibits similar antinociceptive effects in rats. The chronic tolerance to KUST201 actions de-velops less quickly, but the abstinence scores of KUST201 are slightly higher. The activation of δ-opi-oid receptor can synergistically enhance the antinoci-ception mediated by μ-receptor.
