High-grade nucleoside transport inhibition stimulates ventilation in humans.
In 6 healthy male volunteers a placebo-controlled, double-blind, randomized, crossover trial was done to assess the effect of 1, 2, 4, and 6 mg of draflazine, a specific nucleoside transport inhibitor, on ventilation. Draflazine increased thoracic excursions dose-dependently by maximally (median with 95% confidence interval) 114.0% (38.3-184.8%) without affecting breathing rate. Ex vivo adenosine transport was inhibited by 0% (0-1%) after placebo, and 70% (59-74%), 81% (76-85%), 90% (86-93%), and 93% (90-96%) after the 4 increasing draflazine dosages, respectively (P < .05 for each draflazine dosage versus placebo). These results indicate that endogenously released adenosine may play a role in the regulation of ventilation.
Rongen
G A
GA
Department of Internal Medicine, University Hospital Nijmegen, The Netherlands.
Smits
P
P
Bootsma
G
G
Ver Donck
K
K
de Vries
A
A
Thien
T
T
D000241:Adenosine / Q000378:metabolism; D000328:Adult; D001692:Biological Transport / Q000187:drug effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D009705:Nucleosides / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010991:Plethysmography / Q000187:drug effects; D012119:Respiration / Q000187:drug effects*; D013909:Thorax / Q000187:drug effects / Q000502:physiology; D013990:Tidal Volume / Q000187:drug effects
D009705:Nucleosides; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; C072040:draflazine; D000241:Adenosine