Document Detail


Interactions in the behavioral effects of methylxanthines and adenosine derivatives.
MedLine Citation:
PMID:  6194284     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The role of adenosine receptors in behavioral effects of alkylxanthines was evaluated in mice. The relative potencies of alkylxanthines in reversing locomotor activity depression elicited by L-phenylisopropyladenosine (L-PIA) were similar to relative potencies in competing for adenosine receptors labeled by [3H]cyclohexyladenosine. Whereas L-PIA at i.p. doses of 0.10 mumol/kg and higher depressed locomotor activity, lower doses (0.01 and 0.05 mumol/kg) augmented locomotor activity. At the doses evaluated, caffeine did not further augment the L-PIA (0.05 mumol/kg)-enhanced locomotor activity. Low doses of diazepam, like L-PIA, augmented locomotor activity. Combining locomotor depressant doses of diazepam and caffeine produced a paradoxical stimulation of activity, as observed also for L-PIA and caffeine. Low doses of diazepam but not L-PIA increased crossings between the light and dark sites in a shuttle box, indicating a difference in the behavioral profile of these two agents. At behaviorally effective doses, L-PIA did not alter blood pressure or heart rate, but elicited some premature ventricular contractions which, however, occurred to a similar extent at locomotor depressant and stimulant doses of L-PIA. Brain levels of L-PIA at the lowest behaviorally active doses were adequate to occupy more than 50% of adenosine receptors. Thus, the behavioral effects of L-PIA appeared to be mediated in the brain and were not secondary to the cardiovascular effects.
Authors:
J J Katims; Z Annau; S H Snyder
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  227     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1983 Oct 
Date Detail:
Created Date:  1983-11-23     Completed Date:  1983-11-23     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  167-73     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenosine / analogs & derivatives*,  pharmacology
Animals
Blood Pressure / drug effects
Brain / drug effects
Caffeine / pharmacology
Cardiac Complexes, Premature / chemically induced
Diazepam / pharmacology*
Drug Interactions
Heart Rate / drug effects
Male
Mice
Mice, Inbred ICR
Motor Activity / drug effects*
Phenylisopropyladenosine / pharmacology*
Receptors, Cell Surface / drug effects
Receptors, Purinergic
Stimulation, Chemical
Xanthines / pharmacology*
Grant Support
ID/Acronym/Agency:
DA-00266/DA/NIDA NIH HHS; MH-18501/MH/NIMH NIH HHS; NS-16375/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Cell Surface; 0/Receptors, Purinergic; 0/Xanthines; 29193-86-0/Phenylisopropyladenosine; 439-14-5/Diazepam; 58-08-2/Caffeine; 58-61-7/Adenosine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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