title: Differential tolerance to repeated daily injections of N-allylnormetazocine and its enantiomers in the rat.
abstract: This study was designed to compare the development of tolerance to the effects of N-allylnormetazocine (SKF-10,047) and its enantiomers on the EEG and on behavior. Adult female Sprague-Dawley rats were implanted with chronic cortical electroencephalogram (EEG) and electromyogram (EMG) recording electrodes in the temporalis muscle and with permanent cannulae in the external jugular vein. In non-tolerant rats, 10 mg/kg (i.v.) injections of SKF-10,047 racemate produced primarily aroused wakefulness for about 120 min, that was associated with alternation between desynchronized EEG and theta waves in the EEG. After these rats received a series of automatic, intravenous injections of SKF-10,047 racemate, the aroused wakefulness state induced by SKF-10,047 racemate lasted for about 40 min. In non-tolerant rats, 2.5 mg/kg (i.v.) injections of (+)-SKF-10,047 induced a psychotomimetric EEG and behavioral state for about 30 min, which included continuous theta wave activity in the EEG. After chronic treatment with (+)-SKF-10,047, the psychotomimetic state induced by (+)-SKF-10,047 persisted for about 20 min. In non-tolerant rats, 2.5 mg/kg (i.v.) injections of (-)-SKF-10,047 produced an aroused EEG and behavioral wakefulness for about 30 min, which was then followed by slow-wave bursts in the EEG and associated behavioral stupor for about 90 min. After chronic treatment with (-)-SKF-10,047, injection of (-)-SKF-10,047 produced predominantly aroused wakefulness for about 45 min. The data suggest that (+)-SKF-10,047 exerts psychotogenic properties, but not opioid properties. On the other hand, the data suggest that (-)-SKF-10,047 possesses opioid properties.
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D004361:Drug Tolerance; D004569:Electroencephalography; D005260:Female; D006213:Hallucinogens / Q000494:pharmacology; D008297:Male; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects; D012890:Sleep / Q000187:drug effects; D013237:Stereoisomerism
chemical_list: D006213:Hallucinogens; D011957:Receptors, Opioid; C012134:SK&F 10047; D010620:Phenazocine