Effects of inhaled or intravenous thiorphan on substance P-induced airway obstruction.
Male Hartley guinea pigs were treated with the enkephalinase inhibitor thiorphan by inhaled or intravenous administration routes and potentiation of substance P-induced airway obstruction examined. Inhaled thiorphan was several thousand times more potent than intravenous thiorphan. The biologic half-life was less than 5 min for aerosolized thiorphan and greater than 20 min after intravenous administration. The very high potency of aerosolized thiorphan may be a result of its direct targeting to enkephalinase concentrated within the airway epithelium. The short duration of action of inhaled thiorphan may reflect its rapid diffusion from the airway surface.
Silbaugh
S A
SA
Pulmonary Research (MC 931), Lilly Corporate Center, Indianapolis, IN 46285.
Cockerham
S L
SL
Stengel
P W
PW
D000336:Aerosols; D000402:Airway Obstruction / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006168:Guinea Pigs; D007275:Injections, Intravenous; D008168:Lung / Q000503:physiopathology; D008297:Male; D013373:Substance P / Q000008:administration & dosage; D015244:Thiorphan / Q000008:administration & dosage*
D000336:Aerosols; D013373:Substance P; D015244:Thiorphan