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Eur J Pharmacol. 2014 Oct 5;740:455-63. doi: 10.1016/j.ejphar.2014.06.045. Epub 2014 Jul 3.

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.

Author information

1
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.
2
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China.
3
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
4
Phamacology department, China Pharmaceutical University, Nanjing 211198, China.
5
Alcohol & Drug Abuse Research Center, McLean Hospital, Harvard Medical School, MA 02478, USA.
6
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.
7
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.

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.

KEYWORDS:

Antinociception; CPP; Heroin self-administration; Reinstatement of drug-seeking behavior; Sedation; κ agonist and μ agonist/antagonist

PMID:
24998879
DOI:
10.1016/j.ejphar.2014.06.045
[Indexed for MEDLINE]
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