title: KF17837 is an A2 adenosine receptor antagonist in vivo.
abstract: The goal of this study was to determine whether (E)-1,3-dipropyl-7-methyl-8-(3,4-dimethoxystyryl)xanthine (KF17837) is a useful pharmacological probe for investigating in the rat the in vivo physiological roles of A2 adenosine receptors. In anesthetized rats, bradycardic responses to N6-cyclopentyladenosine and hypotensive responses to 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamido adenosine (CGS21680C) were used to assess A1 receptor and A2 receptor activation, respectively. After obtaining control responses to N6-cyclopentyladenosine and CGS21680C, the rats received infusions of either vehicle or one of two dosage levels of KF17837, a compound recently demonstrated to be a potent and selective A2 receptor antagonist in vitro. KF17837 was infused for 4 hr and, at various times during the infusions, bradycardic and hypotensive responses to N6-cyclopentyladenosine and CGS21680C, respectively, were elicited. Infusion of either 10 or 30 micrograms kg-1 min-1 (2.4 or 7.4 mg kg-1 4 hr-1) of KF17837 did not significantly affect the bradycardic responses to N6-cyclopentyladenosine. By contrast, 10 micrograms kg-1 min-1 of KF17837 attenuated and 30 micrograms kg-1 min-1 of KF17837 nearly abolished hypotensive responses to CGS21680C. In a second study, pretreatment with KF17837 (30 micrograms kg-1 min-1) did not affect the hypotensive response to either PGI2 (3 micrograms kg-1 min-1) or acetylcholine (100 micrograms kg-1 min-1); however, it attenuated the hypotensive response to adenosine (300 micrograms kg-1 min-1). In a third study, hypotension was induced and maintained with an infusion of adenosine (300 micrograms kg-1 min-1).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Center for Clinical Pharmacology, University of Pittsburgh Medical Center, Pennsylvania.
authors.forename: E K
authors.initials: EK
authors.lastname: Jackson
authors.forename: W A
authors.initials: WA
authors.lastname: Herzer
authors.forename: F
authors.initials: F
authors.lastname: Suzuki
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003864:Depression, Chemical; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D014970:Xanthines / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D010627:Phenethylamines; D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C081198:KF 17837; C048599:N(6)-cyclopentyladenosine; D000241:Adenosine