Document Detail

Response-rate suppression in operant paradigm as predictor of soporific potency in rats and identification of three novel sedative-hypnotic neuroactive steroids.
MedLine Citation:
PMID:  10565857     Owner:  NLM     Status:  MEDLINE    
Novel neuroactive steroids were evaluated for their effects on operant responding, rotorod motor performance, and electroencephalogram recording in rats. Co 134444, Co 177843, and Co 127501 were compared with the prototypical gamma-aminobutyric acid(A)-positive allosteric modulators triazolam, zolpidem, pentobarbital, pregnanolone, and CCD 3693. Each of the compounds produced a dose-related decrease in response rates under a variable-interval 2-min schedule of positive reinforcement in an operant paradigm. In addition, all compounds produced a dose-related increase in ataxia and significant increases in nonrapid eye movement sleep in this experiment or have been previously reported to do so. Co 134444, Co 177843, and Co 127501 increased nonrapid eye movement sleep at doses that had no effect on rapid eye movement sleep. All of the compounds were more potent at decreasing operant responding than they were at increasing ataxia. Furthermore, the potency of compounds to produce response-rate suppression in an operant paradigm appeared to be a better predictor of soporific potency than did potency in the rotorod assay. The screening for sedative-hypnotic activity resulted in the identification of the novel orally active neuroactive steroids Co 134444, Co 177843, and Co 127501.
K E Vanover; D M Edgar; W F Seidel; D J Hogenkamp; D B Fick; N C Lan; K W Gee; R B Carter
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  291     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1999 Dec 
Date Detail:
Created Date:  1999-12-20     Completed Date:  1999-12-20     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1317-23     Citation Subset:  IM    
CoCensys, Inc., Irvine, California 92618, USA.
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MeSH Terms
Conditioning, Operant / drug effects*
Depression, Chemical
Dose-Response Relationship, Drug
Electroencephalography / drug effects
Hypnotics and Sedatives / pharmacology*
Pentobarbital / pharmacology
Postural Balance / drug effects
Pregnanolone / analogs & derivatives,  pharmacology
Pregnenolone / analogs & derivatives,  pharmacology
Pyridines / pharmacology
Rats, Sprague-Dawley
Rats, Wistar
Steroids / pharmacology*
Triazolam / pharmacology
Reg. No./Substance:
0/Co 127501; 0/Co 134444; 0/Co 177843; 0/Hypnotics and Sedatives; 0/Pyridines; 0/Steroids; 128-20-1/Pregnanolone; 145-13-1/Pregnenolone; 177080-77-2/CCD 3693; 28911-01-5/Triazolam; 76-74-4/Pentobarbital; 82626-48-0/zolpidem

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