Adenosine antagonists reverse the cataleptic effects of haloperidol: implications for the treatment of Parkinson's disease.
The effects of adenosine antagonists were compared in two rodent models of Parkinsonian symptoms. In the first experiment the dopamine D2 antagonist, haloperidol, was used to induce catalepsy. It was found that treatment with the non-selective adenosine antagonist caffeine significantly reduced catalepsy at each dose. Treatment with the selective A1 antagonist CPT also produced a significant reduction in catalepsy, as did treatment with the selective A2A antagonist SCH58261. In the second experiment haloperidol was used to suppress locomotor activity in an open field test. Treatment with caffeine significantly increased locomotion reduced by haloperidol, but not at all doses tested. Treatment with CPT also increased haloperidol-suppressed locomotor activity in dose-dependent manner. Surprisingly, treatment with SCH58261 did not significantly increase locomotor activity in animals treated with haloperidol at any dose tested. While some of these results were unexpected, the overall pattern suggests that adenosine antagonists would be useful as therapies for Parkinsonian patients as they appear to increase movement. The results also suggest that in acute timelines A1 antagonists may be more beneficial than previously supposed.
Trevitt
Jennifer
J
California State University, Fullerton Fullerton, CA 92834, USA. jtrevitt@fullerton.edu
Vallance
Christopher
C
Harris
Allison
A
Goode
Tamara
T
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D010300:Parkinson Disease / Q000188:drug therapy*; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000494:pharmacology
C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines; D014230:Triazoles; D002110:Caffeine; D006220:Haloperidol