title: KF17837: a novel selective adenosine A2A receptor antagonist with anticataleptic activity.
abstract: KF17837 is a novel selective adenosine A2A receptor antagonist. Oral administration of KF17837 (2.5, 10.0 and 30.0 mg/kg) significantly ameliorated the cataleptic responses induced by intracerebroventricular administration of an adenosine A2A receptor agonist, CGS 21680 (10 micrograms), in a dose-dependent manner. KF17837 also reduced the catalepsy induced by haloperidol (1 mg/kg i.p.) and by reserpine (5 mg/kg i.p.). These anticataleptic effects were exhibited dose dependently at doses from 0.625 and 2.5 mg/kg p.o., respectively. Moreover, KF17837 (0.625 mg/kg p.o.) potentiated the anticataleptic effects of a subthreshold dose of L-3,4-dihydroxyphenylalanine (L-DOPA; 25 mg/kg i.p.) plus benserazide (6.25 mg/kg i.p.). These results suggested that KF17837 is a centrally active adenosine A2A receptor antagonist and that the dopaminergic function of the nigrostriatal pathway is potentiated by adenosine A2A receptor antagonists. Furthermore, KF17837 may be a useful drug in the treatment of parkinsonism.
authors.affiliation: Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co. Ltd., Shizuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kanda
authors.forename: S
authors.initials: S
authors.lastname: Shiozaki
authors.forename: J
authors.initials: J
authors.lastname: Shimada
authors.forename: F
authors.initials: F
authors.lastname: Suzuki
authors.forename: J
authors.initials: J
authors.lastname: Nakamura
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000633:toxicity; D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000037:antagonists & inhibitors* / Q000633:toxicity; D001545:Benserazide / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006220:Haloperidol / Q000037:antagonists & inhibitors; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D051379:Mice; D010627:Phenethylamines / Q000037:antagonists & inhibitors* / Q000633:toxicity; D058914:Purinergic Antagonists; D014970:Xanthines / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000959:Antihypertensive Agents; D010627:Phenethylamines; D058914:Purinergic Antagonists; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C081198:KF 17837; D007980:Levodopa; D001545:Benserazide; D006220:Haloperidol; D000241:Adenosine