Abstract
Aim:
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 Ki 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 ED50 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).
Conclusion:
ATPM-ET may have potential as a therapeutic agent for the treatment of drug abuse.
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Acknowledgements
This work was supported by the National Basic Research Program grant from the Ministry of Science and Technology of China (2009CB522000, 2009ZX09301-001), National Natural Science Foundation of China (30873050) and a fund granted by the Chinese Academy of Sciences (KSCX2-YW-R-253).
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Sun, Jf., Wang, Yh., Li, Fy. et al. Effects of ATPM-ET, a novel κ agonist with partial μ activity, on physical dependence and behavior sensitization in mice. Acta Pharmacol Sin 31, 1547–1552 (2010). https://doi.org/10.1038/aps.2010.164
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DOI: https://doi.org/10.1038/aps.2010.164
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