title: Effects of ATPM-ET, a novel κ agonist with partial μ activity, on physical dependence and behavior sensitization in mice.
abstract: OBJECTIVE
  to investigate the effects of ATPM-ET [(-)-3-N-Ethylaminothiazolo [5,4-b]-N-cyclopropylmethylmorphinan hydrochloride] on physical dependence and behavioral sensitization to morphine in mice.
  
  
  METHODS
  the pharmacological profile of ATPM-ET was characterized using competitive binding and GTPγS binding assays. We then examined the antinociceptive effects of ATPM-ET in the hot plate test. Morphine dependence assay and behavioral sensitization assay were used to determine the effect of ATPM-ET on physical dependence and behavior sensitization to morphine in mice.
  
  
  RESULTS
  the binding assay indicated that ATPM-ET ATPM-ET exhibited a high affinity to both κ- and μ-opioid receptors with K(i) values of 0.15 nmol/L and 4.7 nmol/L, respectively, indicating it was a full κ-opioid receptor agonist and a partial μ-opioid receptor agonist. In the hot plate test, ATPM-ET produced a dose-dependent antinociceptive effect, with an ED(50) value of 2.68 (2.34-3.07) mg/kg. Administration of ATPM-ET (1 and 2 mg/kg, sc) prior to naloxone (3.0 mg/kg, sc) injection significantly inhibited withdrawal jumping of mice. In addition, ATPM-ET (1 and 2 mg/kg, sc) also showed a trend toward decreasing morphine withdrawal-induced weight loss. ATPM-ET (1.5 and 3 mg/kg, sc) 15 min before the morphine challenge significantly inhibited the morphine-induced behavior sensitization (P<0.05).
  
  
  CONCLUSIONS
  ATPM-ET may have potential as a therapeutic agent for the treatment of drug abuse.
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Jian-feng
authors.initials: JF
authors.lastname: SUN
authors.forename: Yu-hua
authors.initials: YH
authors.lastname: WANG
authors.forename: Fu-ying
authors.initials: FY
authors.lastname: LI
authors.forename: Gang
authors.initials: G
authors.lastname: LU
authors.forename: Yi-min
authors.initials: YM
authors.lastname: TAO
authors.forename: Yun
authors.initials: Y
authors.lastname: CHENG
authors.forename: Jie
authors.initials: J
authors.lastname: CHEN
authors.forename: Xue-jun
authors.initials: XJ
authors.lastname: XU
authors.forename: Zhi-qiang
authors.initials: ZQ
authors.lastname: CHI
authors.forename: John L
authors.initials: JL
authors.lastname: NEUMEYER
authors.forename: Ao
authors.initials: A
authors.lastname: ZHANG
authors.forename: Jing-gen
authors.initials: JG
authors.lastname: LIU
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D008297:Male; D051379:Mice; D009019:Morphinans / Q000494:pharmacology*; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D010147:Pain Measurement; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000378:metabolism
chemical_list: C557443:3-N-ethylaminothiazolo(5,4-b)-N-cyclopropylmethylmorphinan hydrochloride; D009019:Morphinans; D009292:Narcotic Antagonists; D009294:Narcotics; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009270:Naloxone; D009020:Morphine