Tremorolytic effects of adenosine A2A antagonists: implications for parkinsonism.
Drug-induced tremulous jaw movements in rats have been used as a model of parkinsonian tremor. Because adenosine A2A antagonists have antiparkinsonian effects, the present experiments were conducted to study the ability of adenosine A2A antagonism to reverse the tremulous jaw movements produced by the antipsychotic drugs pimozide, haloperidol and reserpine. In one group of studies, rats received daily injections of the dopamine antagonist pimozide, and on day 8 they received injections of pimozide plus various doses of the A2A antagonists KW 6002 or MSX-3. KW 6002 and MSX-3 suppressed pimozide-induced tremulous jaw movements, reduced catalepsy, and increased locomotion. MSX-3 also suppressed the jaw movements induced by haloperidol and reserpine. In addition, local injections of MSX-3 into the ventrolateral neostriatum suppressed pimozide-induced tremulous jaw movements. Thus, adenosine A2A antagonism can reverse the tremulous movements induced by antipsychotic drugs, which is consistent with the hypothesis that antagonism of adenosine A2A receptors can result in antiparkinsonian effects. Adenosine A2A antagonists may be useful for their tremorolytic effects, and may help in treating both idiopathic and antipsychotic-induced parkinsonian symptoms.
Salamone
John D
JD
Department of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA. john.salamone@uconn.edu
Betz
Adrienne J
AJ
Ishiwari
Keita
K
Felsted
Jennifer
J
Madson
Lisa
L
Mirante
Brian
B
Clark
Karen
K
Font
Laura
L
Korbey
Samantha
S
Sager
Thomas N
TN
Hockemeyer
Jorg
J
Muller
Christa E
CE
D058917:Adenosine A2 Receptor Antagonists; D002375:Catalepsy / Q000139:chemically induced*; D006801:Humans; D007571:Jaw Diseases / Q000139:chemically induced*; D008124:Locomotion / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009069:Movement Disorders / Q000209:etiology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced*; D010868:Pimozide / Q000009:adverse effects; D011687:Purines / Q000627:therapeutic use; D014202:Tremor / Q000139:chemically induced*; D014970:Xanthines / Q000009:adverse effects
D058917:Adenosine A2 Receptor Antagonists; C113602:MSX 3 compound; D011687:Purines; D014970:Xanthines; D010868:Pimozide; C111599:istradefylline