title: Muscular and cardiac adenosine-induced pain is mediated by A1 receptors.
abstract: OBJECTIVE
  This study attempted to establish whether bamiphylline, a selective antagonist of A1 adenosine receptors, prevents the algogenic effects of adenosine in humans.
  
  
  BACKGROUND
  Experimental findings indicate that the sympathoexcitatory response elicited by adenosine is mediated by A1 receptors.
  
  
  METHODS
  An intrailiac infusion of increasing doses (from 125 to 2,000 micrograms/min) of adenosine was given to 20 patients. Adenosine infusion was then repeated after intrailiac infusion of either bamiphylline or saline solution. In 14 other patients with angina, increasing doses of adenosine (from 108 to 1,728 micrograms/min) were infused into the left coronary artery. Adenosine infusion was then repeated after the intravenous infusion of either bamiphylline or placebo. Coronary blood flow velocity was monitored by a Doppler catheter. Data relative to pain severity are expressed as median and all other data as mean value +/- 1 SD.
  
  
  RESULTS
  Bamiphylline prolonged the time to pain onset caused by the intrailiac adenosine infusion from 444 +/- 96 to 749 +/- 120 s (p < 0.001) and reduced pain severity from 45 to 24 mm (p < 0.01). After placebo infusion, the time to pain onset and pain severity were similar to that of baseline (428 +/- 112 vs. 430 +/- 104 s, p = 0.87 and 44 vs. 43 mm, p = 0.67, respectively). Bamiphylline prolonged the time to pain onset caused by intracoronary adenosine infusion from 519 +/- 128 to 603 +/- 146 s (p < 0.01) and reduced pain severity from 58 to 28 mm (p < 0.02). After placebo infusion, the time to pain onset and pain severity were similar to that at baseline (542 +/- 87 vs. 551 +/- 79 s, p = 0.14 and 55 vs. 50 mm, p = 0.61). Maximal coronary blood flow velocities before and after bamiphylline administration were similar (47 +/- 22 vs. 49 +/- 24 cm/s, p = 0.36) as well as before and after placebo administrtion (40 +/- 20 vs. 41 +/- 20 cm/s, p = 0.07).
  
  
  CONCLUSIONS
  Bamiphylline reduces adenosine-induced muscular and cardiac pain but does not affect adenosine-induced coronary vasodilation. These findings indicate that at the dose used in this study, bamiphylline does not detectably block vascular A2-receptor-mediated adenosine effects in humans, which suggests that the muscular and cardiac algogenic effects of adenosine are mediated mainly by A1 receptors.
authors.affiliation: Divisione di Cardiochirurgia, Università di Roma Tor Vergata, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Gaspardone
authors.forename: F
authors.initials: F
authors.lastname: Crea
authors.forename: F
authors.initials: F
authors.lastname: Tomai
authors.forename: F
authors.initials: F
authors.lastname: Versaci
authors.forename: M
authors.initials: M
authors.lastname: Iamele
authors.forename: G
authors.initials: G
authors.lastname: Gioffrè
authors.forename: L
authors.initials: L
authors.lastname: Chiariello
authors.forename: P A
authors.initials: PA
authors.lastname: Gioffrè
mesh_terms: D000241:Adenosine / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000700:Analgesics / Q000008:administration & dosage; D000787:Angina Pectoris / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007083:Iliac Artery; D007261:Infusions, Intra-Arterial; D008297:Male; D008875:Middle Aged; D009135:Muscular Diseases / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D010146:Pain / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D010147:Pain Measurement; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1 / Q000187:drug effects* / Q000502:physiology; D013806:Theophylline / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000700:Analgesics; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D013806:Theophylline; D000241:Adenosine; C006683:bamifylline