Adenosine A2A receptors modify motor function in MPTP-treated common marmosets.
Both adenosine A1 and A2 receptor populations are located in the striatum and can modify locomotor activity, and they may form a therapeutic target for Parkinson's disease (PD). Administration of the selective adenosine A2A antagonist (E)-1,3-diethyl-8-(3,4-dimethoxystyryl)-7-methyl-3,7-dihydro-1H-pu rine-2,6-dione (KW-6002) to MPTP-treated common marmosets increased locomotor activity. In contrast, administration of the selective A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxantine (DPCPX) had no effect on locomotion. Administration of the adenosine A2A receptor agonist 2-[p-[2-(2-aminoethylamino) carbonylethyl] phenethyl amino]-5'-N-ethylcarboxamidoadenosine (APEC) dose dependently suppressed basal locomotor activity. A minimally effective dose of APEC (0.62 mg/kg, i.p) completely reversed the increase in locomotor activity produced by administration of KW-6002. The adenosine A2A receptor appears to be an important target for the treatment of basal ganglia disorders, particularly PD.
Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co Ltd, Shizuoka, Japan.
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Kanda
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Tashiro
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Kuwana
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Jenner
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002144:Callithrix; D004298:Dopamine; D005260:Female; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009068:Movement / Q000502:physiology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D010627:Phenethylamines / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D011687:Purines / Q000494:pharmacology; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000502:physiology*
D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D011687:Purines; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; C063208:2-((2-aminoethylamino)carbonylethylphenylethylamino)-5'-N-ethylcarboxamidoadenosine; C111599:istradefylline; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000241:Adenosine; D004298:Dopamine