title: Pharmacological characterization and therapeutic potential for the treatment of opioid abuse with ATPM-ET, an N-ethyl substituted aminothiazolomorphinan with κ agonist and μ agonist/antagonist activity.
abstract: We previously reported that the κ agonists with mixed μ activity could attenuate heroin self-administration with less potential to develop tolerance. The present study further investigated the effects of (-)-3-N-Ethylamino-thiazolo[5,4-b]-N-cyclopropylmethylmorphinan hydrochloride (ATPM-ET), a κ agonist and μ agonist/antagonist, on the acquisition and reinstatement of morphine-induced conditioned place preference (CPP), heroin self-administration and heroin-primed reinstatement of drug-seeking behavior. We found that ATPM-ET produced a longer duration of potent antinociceptive effects with less side effect of sedation. More importantly, ATPM-ET attenuated the acquisition of morphine-induced CPP, without affecting the reinstatement of morphine CPP. Furthermore, ATPM-ET significantly inhibited heroin self-administration and the reinstatement of heroin primed drug-seeking behavior. Taken together, ATPM-ET, a novel κ agonist and μ agonist/antagonist may have utility for the treatment of drug dependence.
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China; Department of Physiology, Norman Bethune Medical College, Jilin University, Changchun 130021, China.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Sun
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
authors.forename: Jing-Rui
authors.initials: JR
authors.lastname: Chai
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
authors.forename: Fu-Ying
authors.initials: FY
authors.lastname: Li
authors.affiliation: Phamacology department, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Ai
authors.initials: A
authors.lastname: Hang
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Tao
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Chi
authors.affiliation: Alcohol & Drug Abuse Research Center, McLean Hospital, Harvard Medical School, MA 02478, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Neumeyer
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
authors.forename: Ao
authors.initials: A
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China. Electronic address: jgliu@mail.shcnc.ac.cn.
authors.forename: Jing-Gen
authors.initials: JG
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China. Electronic address: yjwang@mail.simm.ac.cn.
authors.forename: Yu-Jun
authors.initials: YJ
authors.lastname: Wang
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage; D000818:Animals; D003213:Conditioning, Psychological; D058999:Drug-Seeking Behavior / Q000187:drug effects; D006556:Heroin Dependence / Q000188:drug therapy*; D008297:Male; D051379:Mice; D009019:Morphinans / Q000627:therapeutic use*; D009020:Morphine / Q000008:administration & dosage; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000037:antagonists & inhibitors*; D012646:Self Administration
chemical_list: C557443:3-N-ethylaminothiazolo(5,4-b)-N-cyclopropylmethylmorphinan hydrochloride; D000701:Analgesics, Opioid; D009019:Morphinans; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009020:Morphine
keywords: Antinociception; CPP; Heroin self-administration; Reinstatement of drug-seeking behavior; Sedation; κ agonist and μ agonist/antagonist