State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
Acta Pharmacol Sin. 2010 Dec;31(12):1547-52. doi: 10.1038/aps.2010.164. Epub 2010 Nov 22.
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.
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.
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).
ATPM-ET may have potential as a therapeutic agent for the treatment of drug abuse.
研究 ATPM-ET[(-)-3-N-乙基氨基噻唑并[5,4-b]-N-环丙基甲吗啡盐酸盐]对小鼠吗啡身体依赖和行为敏化的影响。
采用竞争性结合和 GTPγS 结合试验对 ATPM-ET 的药理学特性进行了表征。然后，我们在热板试验中检查了 ATPM-ET 的镇痛作用。采用吗啡依赖试验和行为敏化试验来确定 ATPM-ET 对小鼠吗啡身体依赖和行为敏化的影响。
结合试验表明，ATPM-ET 对 κ-和 μ-阿片受体均表现出高亲和力，Ki 值分别为 0.15 nmol/L 和 4.7 nmol/L，表明其为完全 κ-阿片受体激动剂和部分 μ-阿片受体激动剂。在热板试验中，ATPM-ET 产生剂量依赖性镇痛作用，ED50 值为 2.68（2.34-3.07）mg/kg。ATPM-ET（1 和 2 mg/kg，sc）给药在前纳洛酮（3.0 mg/kg，sc）注射前显著抑制了小鼠的戒断跳跃。此外，ATPM-ET（1 和 2 mg/kg，sc）也显示出降低吗啡戒断引起的体重减轻的趋势。ATPM-ET（1.5 和 3 mg/kg，sc）在吗啡攻击前 15 分钟给药显著抑制了吗啡引起的行为敏化（P<0.05）。
ATPM-ET 可能具有作为治疗药物滥用的治疗剂的潜力。
