Oral tremor induced by the muscarinic agonist pilocarpine is suppressed by the adenosine A2A antagonists MSX-3 and SCH58261, but not the adenosine A1 antagonist DPCPX.
Tremulous jaw movements in rats, which can be induced by dopamine (DA) antagonists, DA depletion, and cholinomimetics, have served as a useful model for studies of tremor. Although adenosine A(2A) antagonists can reduce the tremulous jaw movements induced by DA antagonists and DA depletion, there are conflicting reports about the interaction between adenosine antagonists and cholinomimetic drugs. The present studies investigated the ability of adenosine antagonists to reverse the tremorogenic effect of the muscarinic agonist pilocarpine. While the adenosine A(2A) antagonist MSX-3 was incapable of reversing the tremulous jaw movements induced by the 4.0mg/kg dose of pilocarpine, both MSX-3 and the adenosine A(2A) antagonist SCH58261 reversed the tremulous jaw movements elicited by 0.5mg/kg pilocarpine. Systemic administration of the adenosine A(1) antagonist DPCPX failed to reverse the tremulous jaw movements induced by either an acute 0.5mg/kg dose of the cholinomimetic pilocarpine or the DA D2 antagonist pimozide, indicating that the tremorolytic effects of adenosine antagonists may be receptor subtype specific. Behaviorally active doses of MSX-3 and SCH 58261 showed substantial in vivo occupancy of A(2A) receptors, but DPCPX did not. The results of these studies support the use of adenosine A(2A) antagonists for the treatment of tremor.
Collins
Lyndsey E
LE
Department of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA.
Galtieri
Daniel J
DJ
Brennum
Lise T
LT
Sager
Thomas N
TN
Hockemeyer
Jörg
J
Müller
Christa E
CE
Hinman
James R
JR
Chrobak
James J
JJ
Salamone
John D
JD
D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007568:Jaw / Q000187:drug effects*; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D010862:Pilocarpine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D014202:Tremor / Q000139:chemically induced / Q000188:drug therapy*; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use; D014970:Xanthines / Q000494:pharmacology* / Q000627:therapeutic use
C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; C113602:MSX 3 compound; D018721:Muscarinic Agonists; D011743:Pyrimidines; D014230:Triazoles; D014970:Xanthines; D010862:Pilocarpine; D010868:Pimozide; C051360:1,3-dipropyl-8-cyclopentylxanthine