Discriminative stimulus effects of BAY 38-7271, a novel cannabinoid receptor agonist
Discriminative stimulus effects of BAY 38-7271, a novel cannabinoid receptor agonist
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DOI：
10.1016/s0014-2999(02)02697-3
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发表时间：
2002-12-20
影响因子：
5
通讯作者：
Jentzsch, KR
中科院分区：
文献类型：
--
作者：
De Vry, J;Jentzsch, KR
BAY 38-7271 [（-）-（R）-3-（2-羟甲基茚满基-4-氧基）苯基-4，4，4-三氟-1-磺酸盐]是一种新型、高效和选择性的大麻素CB 1/CB 2受体激动剂，具有神经保护特性。本研究的目的是在高度灵敏的体内测定中进一步证实其大麻素CB 1受体激动剂特性。训练雄性Wistar大鼠（n = 24）辨别BAY 38-7271（0.05 mg/kg，i. p.，t-30 min），以固定比例：10，食品强化的两级标准程序。这些动物在52次训练后获得了辨别力。BAY 38-7271在不同的给药途径后测试时具有剂量依赖性（ED 50：0.018 mg/kg，i. p.; 0.001 mug/kg，静脉注射; 0.18 mg/kg，p.o.）。时间依赖性研究表明，提示（0.05 mg/kg，i. p.）在15 min和4 h之间可检测到，在给药后30 min获得最大泛化。用选择性大麻素CB 1受体拮抗剂SR 141716 A [N-（哌啶-1-基）-5-（4-氯苯基）-1-（2，4-二氯苯基）-4-甲基-1H-吡唑-3-甲酰胺盐酸盐]预处理完全拮抗BAY 38-7271的作用（ID 50：1.1 mg/kg，腹腔注射）。在腹膜内给予参比大麻素CB 1受体激动剂HU-210 [（-）-11-OH-δ（8）-四氢大麻酚-二甲基庚基，ED 50：0.003 mg/kg]，CP 55，940 {（-）-顺式-3-[2-羟基-4-甲基-1，2-二氧杂环戊烯-2-基（1，1-二甲基-庚基）苯基]-反式-4-（3-羟丙基）环己醇，0.007 mg/kg}，WIN 55，212 -2 [（R）-4，5-二氢-2-甲基-4（4-吗啉基甲基）-1-（1-萘基羰基）-6H-吡咯并[3，2，1-ij]喹啉-6-酮，0.28 mg/kg]和（-）δ（9）-四氢大麻酚（0.34 mg/kg）。本研究证实BAY 38-7271是体内高效大麻素CB 1受体激动剂。(C)2002 Elsevier Science B. V.保留所有权利。
BAY 38-7271 [(-)-(R)-3-(2-hydroxymethylindanyl-4-oxy)phenyl-4,4,4-trifluoro-1-sulfonate] is a novel, highly potent and selective cannabinoid CB1/CB2 receptor agonist with neuroprotective properties. It was the aim of the present study to further confirm its cannabinoid CB1 receptor agonist properties in a highly sensitive in vivo assay. Male Wistar rats (n = 24) were trained to discriminate BAY 38-7271 (0.05 mg/kg, i.p., t-30 min) from vehicle in a fixed-ratio:10, food-reinforced two-lever standard procedure. The animals acquired the discrimination after a median number of 52 training sessions. BAY 38-7271 generalized dose-dependently when tested after different routes of administration (ED50: 0.018 mg/kg, i.p.; 0.001 mug/kg, i.v.; 0.18 mg/kg, p.o.). A time-dependency study indicated that the cue (0.05 mg/kg, i.p.) was detectable between 15 min and 4 h, with a maximum of generalization obtained at 30 min after administration. Pretreatment with the selective cannabinoid CB1 receptor antagonist SR 141716A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride] completely antagonized the effects of BAY 38-7271 (ID50: 1.1 mg/kg, i.p.). Dose-dependent and complete generalization was also obtained after i.p. administration of the reference cannabinoid CB1 receptor agonists HU-210 [( -)-11-OH-Delta(8)-tetrahydrocannabinol-dimethylheptyl, ED50: 0.003 mg/kg], CP 55,940 {(-)-cis-3-[2-hydroxy-4(1,1-dimethyl-heptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol, 0.007 mg/kg}, WIN 55,212-2 [(R)-4,5-dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphtalenylcarbonyl)-6H-pyrrolo [3,2,1-ij] quinolin-6-one, 0.28 mg/kg] and (-)Delta(9)-tetrahydrocannabinol (0.34 mg/kg). The present study confirms that BAY 38-7271 is a highly potent cannabinoid CB1 receptor agonist in vivo. (C) 2002 Elsevier Science B.V. All rights reserved.