Abstract
AWD 131-138 {1-(4-chlorophenyl)-4-morpholino-imidazolin-2-one}, a new low-affinity partial benzodiazepine receptor agonist with potent anticonvulsant and anxiolytic properties in rodent models, was studied in squirrel monkeys trained to discriminate intramuscular (i.m.) injections of midazolam (0.3 mg/kg) from injections of vehicle. Diazepam produced midazolam-like responding at cumulative doses of 1.0 and 3.0 mg/kg i.m. and decreased rates of responding at 3.0 mg/kg (plasma levels of about 400 ng/ml). In contrast, AWD 131-138 did not produce midazolam-like responding or alter response rates at cumulative doses up to 18.0 mg/kg i.m. (plasma levels over 2100 ng/ml). Other monkeys were trained to intravenously (i.v.) self-administer cocaine (56.0 μg/kg/injection). When AWD 131-138 (10-100 μg/kg/injection) was studied by substitution, responding declined to vehicle substitution levels within three sessions. At the dose of 100 μg/kg i.v. AWD 131-138, sufficient drug was self-administered during the first session (about 3.5 mg/kg) to produce plasma levels above 1000 ng/ml, yet responding over the next two sessions dropped to vehicle levels. The failure of AWD 131-138 to produce benzodiazepine-like discriminative effects and the absence of drug self-administration behavior when substituted for cocaine suggest that its abuse liability is low.
Original language | English (US) |
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Pages (from-to) | 257-265 |
Number of pages | 9 |
Journal | European Journal of Pharmacology |
Volume | 465 |
Issue number | 3 |
DOIs | |
State | Published - Apr 4 2003 |
Keywords
- AWD 131-138
- Anticonvulsant
- Benzodiazepine
- Diazepam
- Drug discrimination
- Midazolam
- Monkey
- Self-administration
ASJC Scopus subject areas
- Pharmacology