Cataleptic effects of gamma-hydroxybutyrate (GHB), its precursor gamma-butyrolactone (GBL), and GABAB receptor agonists in mice: differential antagonism by the GABAB receptor antagonist CGP35348.
Cataleptic effects of gamma-hydroxybutyrate (GHB), its precursor gamma-butyrolactone (GBL), and GABAB receptor agonists in mice: differential antagonism by the GABAB receptor antagonist CGP35348.
复制标题
γ-羟基丁酸 (GHB)、其前体 γ-丁内酯 (GBL) 和 GABAB 受体激动剂对小鼠的强直作用：GABAB 受体拮抗剂 CGP35348 的差异拮抗作用。
DOI：
10.1007/s00213-007-0718-y
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发表时间：
2007
影响因子：
3.4
通讯作者：
Coop,Andrew
中科院分区：
文献类型：
--
作者：
Koek,Wouter;Mercer,SusanL;Coop,Andrew
γ-羟基丁酸盐（GHB）用于治疗嗜睡症，但也被滥用。GHB与GHB受体激动剂巴氯芬有许多共同的作用。目的进一步研究GHB受体在GHB作用中的作用。材料与方法实验检测GHB受体拮抗剂CGP 35348减轻GHB诱导的僵住症的能力，并与GHB受体激动剂减轻僵住症的能力进行比较。GABA受体激动剂巴氯芬和SKF 97541都产生僵住症但效力不同（即，SKF 97541>巴氯芬>GBL>GHB）和起效。在每种化合物的峰值效应时，即，CGP 35348给药后60 min，巴氯芬、SKF 97541、GHB和GBL给药后60、30、30和15 min。在100 mg/kg时，CGP 35348使巴氯芬和SKF 97541的量效曲线右移，但对GHB和GBL的量效曲线无影响;在320 mg/kg时，结论CGP 35348对GHB和GBL的拮抗作用比巴氯芬和SKF 97541弱约3倍，进一步证明了CGP 35348的作用机制可能与其对GHB和GBL的拮抗作用有关。介导GHB和GABAB激动剂的作用是不相同的。GABA B受体亚型的不同参与，或与GABA B受体的不同相互作用，可能解释为什么GHB对治疗发作性睡病有效，而巴氯芬却不被滥用。
RationaleGamma-hydroxybutyrate (GHB) is used to treat narcolepsy but is also abused. GHB has many actions in common with the GABABreceptor agonist baclofen.ObjectiveTo further study the role of GABABreceptors in the effects of GHB.Materials and methodsThe experiments examined the ability of the GABABreceptor antagonist CGP35348 to attenuate GHB-induced catalepsy in comparison with its ability to attenuate the cataleptic effects of GABABreceptor agonists.ResultsIn C57BL/6J mice, GHB, the GHB precursor gamma-butyrolactone (GBL), and the GABABreceptor agonists baclofen and SKF97541 all produced catalepsy but differed in potency (i.e., SKF97541>baclofen>GBL>GHB) and in onset of action. The cataleptic effects of drug combinations were assessed at the time of peak effect of each compound, i.e., 60 min after CGP35348 and 60, 30, 30, and 15 min after baclofen, SKF97541, GHB, and GBL, respectively. At 100 mg/kg, CGP35348 shifted the dose–response curves of baclofen and SKF97541 to the right but not those of GHB and GBL; at 320 mg/kg, CGP35348 shifted the curves of all four compounds to the right.ConclusionsThe finding that CGP35348 was about threefold less potent to antagonize GHB and GBL than baclofen and SKF97541 is further evidence that the mechanisms mediating the effects of GHB and GABABagonists are not identical. Differential involvement of GABABreceptor subtypes, or differential interactions with GABABreceptors, may possibly explain why GHB is effective for treating narcolepsy and is abused whereas baclofen is not.