Fantegrossi William E, Gray Bradley W, Bailey Jessica M, Smith Douglas A, Hansen Martin, Kristensen Jesper L
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Mail Slot 638, 4301 West Markham Street, Little Rock, AR, 72205, USA,
Psychopharmacology (Berl). 2015 Mar;232(6):1039-47. doi: 10.1007/s00213-014-3739-3. Epub 2014 Sep 17.
2-([2-(4-cyano-2,5-dimethoxyphenyl)ethylamino]methyl)phenol (25CN-NBOH) is structurally similar to N-benzyl substituted phenethylamine hallucinogens currently emerging as drugs of abuse. 25CN-NBOH exhibits dramatic selectivity for 5-HT2A receptors in vitro, but has not been behaviorally characterized.
25CN-NBOH was compared to the traditional phenethylamine hallucinogen R(-)-2,5-dimethoxy-4-iodoamphetamine (DOI) using mouse models of drug-elicited head twitch behavior and drug discrimination.
Drug-elicited head twitches were quantified for 10 min following administration of various doses of either DOI or 25CN-NBOH, with and without pretreatments of 0.01 mg/kg 5-HT2A antagonist M100907 or 3.0 mg/kg 5-HT2C antagonist RS102221. The capacity of 25CN-NBOH to attenuate DOI-elicited head twitch was also investigated. Mice were trained to discriminate DOI or M100907 from saline, and 25CN-NBOH was tested for generalization.
25CN-NBOH induced a head twitch response in the mouse that was lower in magnitude than that of DOI, blocked by M100907, but not altered by RS102221. DOI-elicited head twitch was dose-dependently attenuated by 25CN-NBOH pretreatment. 25CN-NBOH produced an intermediate degree of generalization (55 %) for the DOI training dose, and these interoceptive effects were attenuated by M100907. Finally, 25CN-NBOH did not generalize to M100907 at any dose, but ketanserin fully substituted in these animals.
25CN-NBOH was behaviorally active, but less effective than DOI in two mouse models of hallucinogenic effects. The effectiveness with which M100907 antagonized the behavioral actions of 25CN-NBOH strongly suggests that the 5-HT2A receptor is an important site of agonist action for this compound in vivo.
2-([2-(4-氰基-2,5-二甲氧基苯基)乙基氨基]甲基)苯酚（25CN-NBOH）在结构上与目前作为滥用药物出现的N-苄基取代苯乙胺类致幻剂相似。25CN-NBOH在体外对5-HT2A受体表现出显著的选择性，但尚未进行行为学特征描述。
使用药物诱发的头部抽搐行为和药物辨别小鼠模型，将25CN-NBOH与传统苯乙胺类致幻剂R(-)-2,5-二甲氧基-4-碘苯丙胺（DOI）进行比较。
在给予不同剂量的DOI或25CN-NBOH后，对药物诱发的头部抽搐进行10分钟的量化，分别在有和没有预先给予0.01mg/kg 5-HT2A拮抗剂M100907或3.0mg/kg 5-HT2C拮抗剂RS102221的情况下进行。还研究了25CN-NBOH减弱DOI诱发的头部抽搐的能力。训练小鼠将DOI或M100907与生理盐水区分开来，并对25CN-NBOH进行泛化测试。
25CN-NBOH在小鼠中诱发了头部抽搐反应，其幅度低于DOI，可被M100907阻断，但不受RS102221影响。预先给予25CN-NBOH可剂量依赖性地减弱DOI诱发的头部抽搐。25CN-NBOH对DOI训练剂量产生了中等程度的泛化（55%），并且这些内感受效应可被M100907减弱。最后，25CN-NBOH在任何剂量下都不会泛化到M100907，但酮色林在这些动物中可完全替代。
在两种致幻作用小鼠模型中，25CN-NBOH具有行为活性，但效果不如DOI。M100907拮抗25CN-NBOH行为作用的有效性强烈表明，5-HT2A受体是该化合物在体内激动剂作用的重要位点。
