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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
Author(s) -
Rezvani Amir H.,
Overstreet David H.,
Levin Edward D.,
Rosenthal Daniel I.,
Kordik Cheryl P.,
Reitz Allen B.,
Vaidya Anil H.
Publication year - 2007
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2006.00264.x
Subject(s) - naltrexone , alcohol , ethanol , anxiolytic , chemistry , acetamide , pharmacology , alcohol use disorder , medicine , endocrinology , biochemistry , opioid , organic chemistry , receptor
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.