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.
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.
Rezvani
Amir H
AH
Department of Psychiatry, Duke University, Durham, NC, USA.
Overstreet
David H
DH
Levin
Edward D
ED
Rosenthal
Daniel I
DI
Kordik
Cheryl P
CP
Reitz
Allen B
AB
Vaidya
Anil H
AH
D000208:Acute Disease; D000428:Alcohol Drinking / Q000188:drug therapy* / Q000235:genetics*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004361:Drug Tolerance; D007274:Injections, Intraperitoneal; D008297:Male; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats
D014151:Anti-Anxiety Agents; C517656:JNJ-5234801; D009292:Narcotic Antagonists; D010880:Piperidines; D011725:Pyridines; D009271:Naltrexone