title: Hallucinogen-like effects of 2-([2-(4-cyano-2,5-dimethoxyphenyl) ethylamino]methyl)phenol (25CN-NBOH), a novel N-benzylphenethylamine with 100-fold selectivity for 5-HT₂A receptors, in mice.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Mail Slot 638, 4301 West Markham Street, Little Rock, AR, 72205, USA, wefantegrossi@uams.edu.
authors.forename: William E
authors.initials: WE
authors.lastname: Fantegrossi
authors.forename: Bradley W
authors.initials: BW
authors.lastname: Gray
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Bailey
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Smith
authors.forename: Martin
authors.initials: M
authors.lastname: Hansen
authors.forename: Jesper L
authors.initials: JL
authors.lastname: Kristensen
mesh_terms: D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005464:Fluorobenzenes / Q000494:pharmacology; D006213:Hallucinogens / Q000494:pharmacology*; D019416:Head Movements / Q000187:drug effects*; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D051379:Mice; D010627:Phenethylamines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology
chemical_list: D000662:Amphetamines; D005464:Fluorobenzenes; D006213:Hallucinogens; D010627:Phenethylamines; D010880:Piperidines; D044402:Receptor, Serotonin, 5-HT2A; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; C041336:4-iodoamphetamine; C029261:phenethylamine; D007650:Ketanserin; C079049:volinanserin