Comparison of deramciclane to benzodiazepine agonists in behavioural activity of mice and in alcohol drinking of alcohol-preferring rats.
Interactions between alcohol and traditional benzodiazepine anxiolytics hamper the treatment of alcoholism-related anxiety disorders. Serotonin 5-HT(2) receptor antagonists, such as deramciclane, are anxiolytic, and considering their pharmacological profile, they might benefit alcoholics with comorbid anxiety. We studied the effects of acute deramciclane (1, 3 and 10 mg/kg i.p.) on alcohol drinking of alcohol-preferring AA rats drinking 10% (vol/vol) ethanol solution in a 4-h limited-access paradigm. Thereafter, a 5-day repeated-treatment experiment was carried out, under corresponding test design, with deramciclane (3 mg/kg i.p.) as a test drug and midazolam (1 mg/kg i.p.) as a benzodiazepine reference compound. Deramciclane had no effect on alcohol consumption in either acute or repeated dosing study. Midazolam increased ethanol drinking, as expected, when administered on successive days. A modified functional observational battery (FOB) procedure was applied to study neurological, behavioural and autonomic effects induced by deramciclane (1-30 mg/kg po) and diazepam (1-30 mg/kg po) in mice at 30 min, 2 h and 4 h after dosing. Deramciclane had a mild dopamine D(2) receptor antagonism-like effect at the highest dose. The effects of diazepam were predictable, myorelaxation-induced motor impairment and anxiolysis-related hyperlocomotion in a novel environment being the characteristic features at the two highest doses. Deramciclane appears to be a safe and well-tolerated drug and we suggest that it might be useful in the treatment of anxiety in alcoholics.
Ingman
Kimmo
K
Department of Pharmacology and Clinical Pharmacology, University of Turku, Itäinen Pitkäkatu 4B, FIN-20520 Turku, Finland. kiming@utu.fi
Sallinen
Jukka
J
Honkanen
Aapo
A
Korpi
Esa R
ER
D000428:Alcohol Drinking / Q000188:drug therapy* / Q000235:genetics; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology* / Q000627:therapeutic use; D001892:Camphanes / Q000494:pharmacology* / Q000627:therapeutic use; D003975:Diazepam / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D058785:GABA-A Receptor Agonists; D008297:Male; D051379:Mice; D008874:Midazolam / Q000494:pharmacology / Q000627:therapeutic use; D009043:Motor Activity / Q000187:drug effects* / Q000235:genetics; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology
D001892:Camphanes; D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D001569:Benzodiazepines; C060555:deramciclane; D003975:Diazepam; D008874:Midazolam