Effects of atypical anxiolytic N-phenyl-2-[1-[3-(2-pyridinylethynyl)benzoyl]-4-piperidine]acetamide (JNJ-5234801) on alcohol intake in alcohol-preferring P rats.

Journal Article (Journal Article)

BACKGROUND: N-Phenyl-2-[1-[3-(2-pyridinylethynyl)benzoyl]-4-piperidine]acetamide (JNJ-5234801) is a structurally novel atypical anxiolytic with an overall in vivo profile in animals suggestive of the potential to show anxiolytic efficacy in humans at doses that will not cause CNS-related side effects. Furthermore, unlike the benzodiazepines, JNJ-5234801 does not have an adverse interaction with ethanol even at doses 20 to 40 times the minimal effective dose in the rat elevated plus maze (MED=1.0 mg/kg, p.o.). METHODS: In the present study, JNJ-5234801 was evaluated for potential efficacy in reducing alcohol intake in alcohol-preferring rats. Alcohol-preferring P rats were allowed to drink water or alcohol (10%, v/v) in a 2-bottle choice procedure. Once stable baselines were established, the acute effects of JNJ-5234801 [(10-40 mg/kg, intraperitoneally (i.p.)] were assessed. In a separate study, chronic treatment with JNJ-5234801 (40 mg/kg once daily, i.p.) for 12 consecutive days was compared with naltrexone (20 mg/kg, twice daily, i.p.). RESULTS: There was a selective dose-dependent reduction in alcohol intake in the alcohol-preferring (P) rats after acute administration of JNJ-5234801 (10-40 mg/kg, i.p.). There were no significant effects on food or water intake. When administered subchronically, both JNJ-5234801 (40 mg/kg once daily, i.p.) and naltrexone (20 mg/kg, twice daily, i.p.) considerably reduced alcohol intake, but tolerance to the alcohol-suppressing effects appeared to occur sooner in the naltrexone-treated group. While both compounds slightly but significantly reduced food intake at the beginning, only JNJ-5234801 increased water intake and decreased alcohol preference. CONCLUSIONS: The novel atypical anxiolytic JNJ-5234801 has a favorable profile effects on alcohol intake and related measures compared with naltrexone, which is recommended for the treatment of alcoholism.

Full Text

Duke Authors

Cited Authors

  • Rezvani, AH; Overstreet, DH; Levin, ED; Rosenthal, DI; Kordik, CP; Reitz, AB; Vaidya, AH

Published Date

  • January 1, 2007

Published In

Volume / Issue

  • 31 / 1

Start / End Page

  • 57 - 63

PubMed ID

  • 17207102

International Standard Serial Number (ISSN)

  • 0145-6008

Digital Object Identifier (DOI)

  • 10.1111/j.1530-0277.2006.00264.x


  • eng

Conference Location

  • England