SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF ETHER AND RELATED ANALOGS OF DELTA-8-TETRAHYDROCANNABINOL, DELTA-9-TETRAHYDROCANNABINOL, AND DELTA-9,11-TETRAHYDROCANNABINOL
SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF ETHER AND RELATED ANALOGS OF DELTA-8-TETRAHYDROCANNABINOL, DELTA-9-TETRAHYDROCANNABINOL, AND DELTA-9,11-TETRAHYDROCANNABINOL
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DOI：
10.1021/jm00115a023
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发表时间：
1991-11-01
影响因子：
7.3
通讯作者：
RAZDAN, RK
中科院分区：
文献类型：
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作者：
COMPTON, DR;PRESCOTT, WR;RAZDAN, RK
本研究的主要目的是合成一系列大麻素类药物的醚类似物，并评估其在小鼠或大鼠中的激动剂和拮抗剂药理特性。小鼠的激动剂和拮抗剂活性通过多重评估程序（运动活动、甩尾潜伏期、低温、环固定）进行评估，大鼠的活性通过判别刺激模式进行评估。此外，新的类似物被评估其与H-3-CP-55,940标记的THC受体位点结合的能力。没有一种大麻素类似物能够减弱DELTA-9-THC （3mg /kg）在大鼠（剂量高达10mg /kg）或小鼠（剂量高达30mg /kg）中的作用。体内活性最低的化合物似乎也不是混合的激动剂/拮抗剂。这些数据表明酚羟基对受体识别（结合）和体内效力很重要。此外，以前被认为无活性的大麻素甲基醚已被发现产生有限的活性。最后，数据表明delta -9,11- thc比以前的报道更有效，并且确实具有药理活性。
The primary goal of this research was to synthesize a series of ether analogues of the cannabinoid drug class and to evaluate their agonist and antagonist pharmacological properties in either the mouse or the rat. Agonist and antagonist activity was evaluated in mice using a multiple-evaluation procedure (locomotor activity, tail-flick latency, hypothermia, ring immobility) and activity in rats determined in a discriminative stimulus paradigm. Additionally, novel analogues were evaluated for their ability to bind to the THC receptor site labeled by H-3-CP-55,940. None of the cannabinoid analogues were capable of attenuating the effects of DELTA-9-THC (3 mg/kg) in either the rat (doses up to 10 mg/kg) or in the mouse (doses up to 30 mg/kg). It also appears that the compounds with minimal in vivo activity are not mixed agonist/antagonists. These data would suggest that the phenolic hydroxyl is important for receptor recognition (binding) and in vivo potency. Additionally, cannabinoid methyl ethers previously considered inactive have been found to produce limited activity. Lastly, data suggest that DELTA-9,11-THC is more potent than previous reports indicated, and does possess pharmacological activity.