benzofurans and Alcoholism

CEE-03-310 is a selective dopamine D1-like receptor antagonist with no appreciable binding affinity for other receptors. Although originally developed by Novo Nordisk A/S as NNC-687 for the treatment of schizophrenia, the company changed its therapeutic focus in the mid-1990s and the full rights to CEE-03-310 and several related compounds were subsequently granted to CeNeS Pharmaceuticals in 1999. CeNeS is currently investigating the drug's potential in the treatment of insomnia and alcohol dependency [340965], [382293], [401496],[416026]. A phase II, double-blind, placebo-controlled trial of CEE-03-310 demonstrated a dose-dependent enhancement of NREM sleep at the beginning of the night without any effects on the quantity of REM sleep [410739].

Topics: Alcoholism; Animals; Benzazepines; Benzofurans; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Dopamine Antagonists; Drugs, Investigational; Humans; Lethal Dose 50; Randomized Controlled Trials as Topic; Receptors, Dopamine D1; Sleep Initiation and Maintenance Disorders; Structure-Activity Relationship; Treatment Outcome

The theme of this year's American Psychiatric Association (APA) meeting was 'Psychiatry: integrating body and mind, heart and soul', with special focus given to advances in basic and cognitive neuroscience and how these may contribute to integrated care of mental health and illness. The program featured numerous tracks and subtracks in areas of interest such as addiction psychiatry, child, adolescent and geriatric psychiatry, and psychosomatic medicine.

Topics: Alcoholism; Benzofurans; Canada; Drug Discovery; Humans; Indoles; Mental Disorders; Piperazines; Psychiatry; Quinolones; Schizophrenia; Thiophenes; Vilazodone Hydrochloride

Previous research has demonstrated that treatment with the positive allosteric modulator (PAM) of the GABA(B) receptor (GABA(B) PAM), rac-BHFF, suppressed lever-responding for alcohol and amount of self-administered alcohol in Sardinian alcohol-preferring (sP) rats. The present study was designed to extend the investigation on the anti-alcohol effects of rac-BHFF to alcohol drinking behavior. To this end, sP rats were exposed to the homecage, 2-bottle "alcohol (10%, v/v) vs water" choice regimen, with unlimited access for 24 h/day. rac-BHFF was administered once daily and for 7 consecutive days at the doses of 0, 50, 100, and 200 mg/kg (i.g.). Treatment with rac-BHFF resulted in an immediate, stable, and dose-related reduction in daily alcohol intake; the overall magnitude of reduction in alcohol intake averaged approximately 25%, 40%, and 65% in 50, 100, and 200 mg/kg rac-BHFF-treated rat groups, respectively. An increase in daily water intake fully compensated the reduction in alcohol intake, so that daily total fluid intake was unaffected by treatment with rac-BHFF. Daily food intake tended to be reduced only by the highest dose of rac-BHFF. These results complement closely with previous data indicating that (a) rac-BHFF suppressed operant, oral alcohol self-administration in sP rats and (b) the prototypic GABA(B) PAMs, CGP7930 and GS39783, reduced alcohol drinking in sP rats. However, while the reducing effect of CGP7930 and GS39783 on the daily alcohol intake tended to vanish after the first 2-3 days of treatment, the reducing effect of rac-BHFF on daily alcohol intake remained unchanged over the entire 7-day treatment period. These data strengthen the hypothesis that GABA(B) PAMs may represent a step forward in the search for GABA(B) receptor ligands with therapeutic potential for alcoholism.

Topics: Alcohol Drinking; Alcoholism; Animals; Benzofurans; Male; Rats; Receptors, GABA-B; Self Administration